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Journal of Nanobiotechnology Jun 2022Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous...
BACKGROUND
Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback.
METHODS AND RESULTS
In the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an HO ON/OFF stimulated model. Enhanced release profiles stimulated by HO were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway.
CONCLUSIONS
Thus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss.
Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Cisplatin; Guinea Pigs; Hearing Loss; Hydrogen Peroxide; Nanoparticles; Ototoxicity; Reactive Oxygen Species; Xanthophylls
PubMed: 35689218
DOI: 10.1186/s12951-022-01485-8 -
The Journal of International Advanced... May 2022Cochlear implants are arguably the most successful neural prosthesis today. Cochlear implantation has several difficulties in patients with internal ear anomalies. This...
BACKGROUND
Cochlear implants are arguably the most successful neural prosthesis today. Cochlear implantation has several difficulties in patients with internal ear anomalies. This study was performed to analyze intraoperative, postoperative findings, and auditory performance of 55 patients who had inner ear malformations and were treated with cochlear implants at Otorhinolaryngology Department of Çukurova University Hospital.
METHODS
Auditory performances were analyzed in 30 of 55 patients. Patients with cochlear anomalies were evaluated as group I, patients with vestibular malformation as group II, and patients with the normal bone labyrinth as group III. Listening progress profiles and meaningful auditory integration scale tests were used to determine performances.
RESULTS
Comparison between the listening progress profiles test performance of the groups at 12th and 18th month of group I was significantly lower than other groups (P < .05) and reached at the same level after the 24th month. Comparison between the meaningful auditory integration scale test performance of groups at 24th and 36th month of group I was significantly lower than other groups (P < .05). Perilymph gusher was observed in 3 patients who had incomplete partition I malformation. Oozing was observed in 50% of incomplete partition II patients. Facial nerve traced a variant course in 4 of 55 patients and 6 patients had postoperative meningitis.
CONCLUSION
Initially patients with inner ear anomalies showed that the level of language development was worse than patients with normal bone anatomy. However, it was shown that they both reached the same point as a result. Facial nerve anomaly and meningitis risk is higher in patients with inner ear malformations.
Topics: Cochlear Implantation; Cochlear Implants; Ear, Inner; Hearing Tests; Humans; Perilymph; Retrospective Studies
PubMed: 35608487
DOI: 10.5152/iao.2022.20134 -
Case Reports in Otolaryngology 2022Eustachian tube dilation (ETD) is an established, minimally invasive therapeutic approach for chronic eustachian tube dysfunction. The complications associated with...
Eustachian tube dilation (ETD) is an established, minimally invasive therapeutic approach for chronic eustachian tube dysfunction. The complications associated with performing a ETD are rare. A 22-year-old female patient presented with chronic otitis media on the right side and chronic obstructive tube dilation disorder on both sides. A type I tympanoplasty was performed on the right side because of a tympanic membrane perforation after a ETD on both sides without apparent complications. On the 5th postoperative day, she presented with headache, dizziness and hearing loss on the right side. There was a decrease of hearing threshold on the right side in the pure-tone audiogram and vHIT, cVEMP, and SVV were irregular. The -2-transferrin test was positive. Since a right-sided perilymph fistula was suspected, an emergency tympanotomy was performed with a round window membrane cover with fascia on the right side. Intraoperatively, a regular, intact ossicular chain was found with a slightly moist middle ear mucosa. The round window membrane was covered by the promontorial lip. Under these measures, the patient's dizziness regressed. The right ear pure-tone threshold vHIT, cVEMP, and SVV normalized.
PubMed: 35578706
DOI: 10.1155/2022/5978757 -
Frontiers in Cell and Developmental... 2022The high complexity of the cellular architecture of the human inner ear and the inaccessibility for tissue biopsy hampers cellular and molecular analysis of inner ear...
The high complexity of the cellular architecture of the human inner ear and the inaccessibility for tissue biopsy hampers cellular and molecular analysis of inner ear disease. Sampling and analysis of perilymph may present an opportunity for improved diagnostics and understanding of human inner ear pathology. Analysis of the perilymph proteome from patients undergoing cochlear implantation was carried out revealing a multitude of proteins and patterns of protein composition that may enable characterisation of patients into subgroups. Based on existing data and databases, single proteins that are not present in the blood circulation were related to cells within the cochlea to allow prediction of which cells contribute to the individual perilymph proteome of the patients. Based on the results, we propose a human atlas of the cochlea. Finally, druggable targets within the perilymph proteome were identified. Understanding and modulating the human perilymph proteome will enable novel avenues to improve diagnosis and treatment of inner ear diseases.
PubMed: 35573665
DOI: 10.3389/fcell.2022.847157 -
PloS One 2022Methotrexate (MTX) has been used in treating various types of cancers but can also cause damage to normal organs and cell types. Folinic acid (FA) is a well-known MTX...
Methotrexate (MTX) has been used in treating various types of cancers but can also cause damage to normal organs and cell types. Folinic acid (FA) is a well-known MTX antidote that protects against toxicity caused by the drug and has been used for decades. Since hearing loss caused by MTX treatment is not well studied, herein we aimed to investigate the efficiency of the antioxidant Avenanthramide-C (AVN-C) on high-dose MTX (HDMTX) toxicity in the ear and provide insights into the possible mechanism involved in MTX-induced hearing loss in normal adult C57Bl/6 mice and HEI-OC1 cells. Our results show that the levels of MTX increased in the serum and perilymph 30 minutes after systemic administration. MTX increased hearing thresholds in mice, whereas AVN-C and FA preserved hearing within the normal range. MTX also caused a decrease in wave I amplitude, while AVN-C and FA maintained it at higher levels. MTX considerably damaged the cochlear synapses and neuronal integrity, and both AVN-C and FA rescued the synapses. MTX reduced the cell viability and increased the reactive oxygen species (ROS) level in HEI-OC1 cells, but AVN-C and FA reversed these changes. Apoptosis- and ROS-related genes were significantly upregulated in MTX-treated HEI-OC1 cells; however, they were downregulated by AVN-C and FA treatment. We show that MTX can cause severe hearing loss; it can cross the blood-labyrinth barrier and cause damage to the cochlear neurons and outer hair cells (OHCs). The antioxidant AVN-C exerts a strong protective effect against MTX-induced ototoxicity and preserved the inner ear structures (synapses, neurons, and OHCs) from MTX-induced damage. The mechanism of AVN-C against MTX suggests that ROS is involved in HDMTX-induced ototoxicity.
Topics: Animals; Antioxidants; Apoptosis; Cell Line; Cisplatin; Hearing Loss; Methotrexate; Mice; Ototoxicity; Reactive Oxygen Species; ortho-Aminobenzoates
PubMed: 35353852
DOI: 10.1371/journal.pone.0266108 -
Metabolites Feb 2022Sensorineural hearing loss is the most common sensory deficit. The etiologies of sensorineural hearing loss have been described and can be congenital or acquired. For... (Review)
Review
Sensorineural hearing loss is the most common sensory deficit. The etiologies of sensorineural hearing loss have been described and can be congenital or acquired. For congenital non-syndromic hearing loss, mutations that are related to sites of cochlear damage have been discovered (e.g., connexin proteins, mitochondrial genes, etc.). For cytomegalovirus infection or auditory neuropathies, mechanisms are also well known and well researched. Although the etiologies of sensorineural hearing loss may be evident for some patients, the damaged sites and pathological mechanisms remain unclear for patients with progressive post-lingual hearing loss. Metabolomics is an emerging technique in which all metabolites present in a sample at a given time are analyzed, reflecting a physiological state. The objective of this study was to review the literature on the use of metabolomics in hearing loss. The findings of this review suggest that metabolomic studies may help to develop objective tests for diagnosis and personalized treatment.
PubMed: 35323657
DOI: 10.3390/metabo12030214 -
Frontiers in Neurology 2022Labyrinthine fistula (LF) is one of the most important complications of cholesteatoma and is defined as an abnormal communication between the inner and the middle ear....
Labyrinthine fistula (LF) is one of the most important complications of cholesteatoma and is defined as an abnormal communication between the inner and the middle ear. This study aims to describe our experience with the partial labyrinthectomy evaluating the post-operative hearing results. Twenty-one patients who presented labyrinthine fistula in the semicircular canals were included in the present study. Hearing impairment was present in 48% of patients (10/21). A pre-operative assessment using the Gardner-Robertson hearing classification showed the following: 52%, Class I; and 48%, Class II. A post-surgical Gardner-Robertson hearing classification evidenced the following: 43%, Class I; and 57%, Class II. The presence of LF is usually considered a negative prognostic factor for hearing preservation. The key point of partial labyrinthectomy surgery is the preservation of structures, keeping them wet with Ringer's solution throughout the procedures, and not performing suction that is close to the opened LF. The bony labyrinth is drilled underwater without suction, removing the entire cholesteatoma matrix and quickly plugging the site before and after the LF. This faster plugging of the labyrinth makes it possible to preserve the peri-lymph and the endo-lymph fluid and the hearing function. This study showed that a partial labyrinthectomy is useful for maintaining serviceable hearing in patients with LF.
PubMed: 35309574
DOI: 10.3389/fneur.2022.804915 -
PloS One 2022Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea...
Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea microenvironment. In order to clarify whether the protein composition of the perilymph can provide new insights into individual hearing performance after cochlear implantation (CI), computational analysis in correlation to clinical performance after CI were performed based on the proteome profile derived from perilymph samples (liquid biopsies). Perilymph samples from cochlear implant recipients have been analyzed by mass spectrometry (MS). The proteins were identified using the shot-gun proteomics method and quantified and analyzed using Max Quant, Perseus and IPA software. A total of 75 perilymph samples from 68 (adults and children) patients were included in the analysis. Speech perception data one year after implantation were available for 45 patients and these were used for subsequent analysis. According to their hearing performance, patients with excellent (n = 22) and poor (n = 14) performance one year after CI were identified and used for further analysis. The protein composition and statistically significant differences in the two groups were detected by relative quantification of the perilymph proteins. With this procedure, a selection of 287 proteins were identified in at least eight samples in both groups. In the perilymph of the patients with excellent and poor performance, five and six significantly elevated proteins were identified respectively. These proteins seem to be involved in different immunological processes in excellent and poor performer. Further analysis on the role of specific proteins as predictors for poor or excellent performance among CI recipients are mandatory. Combinatory analysis of molecular inner ear profiles and clinical performance data using bioinformatics analysis may open up new possibilities for patient stratification. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies.
Topics: Proteome
PubMed: 35239655
DOI: 10.1371/journal.pone.0263765 -
The Journal of International Advanced... Jan 2022Cochlear implant surgery in far-advanced otosclerosis can be challenging due to the degenerative process that affects the cochlea. We used OTOPLAN® to plan and define...
Cochlear implant surgery in far-advanced otosclerosis can be challenging due to the degenerative process that affects the cochlea. We used OTOPLAN® to plan and define the details of surgery in a patient with such severe alteration of the cochlea that cochlear implant could be contraindicated. A 73-year-old man affected by bilateral far-advanced otosclerosis, previously treated by bilateral stapedotomy, presented 0% of speech discrimination using bilateral hearing aids. A unilateral cochlear implant was planned. The patient underwent radiologic investigation pre-surgery with temporal bone computer tomography, magnetic resonance imaging, and OTOPLAN. Radiology confirmed bilaterally advanced signs of fenestral and cochlear otosclerosis with large osteolytic cavities along the whole cochlea leading to the mixture of endolymph and perilymph. The OTOPLAN identified the alteration of the cochlea in detail. Based on the results of the software, we used a perimodiolar implant on the left ear. No intraoperative or post-operative surgical complications were observed. The patient was checked 6 months after surgery, he did not refer any problems and obtained 75% of speech discrimination at 65 dB. Our case suggests that OTOPLAN is a useful tool in far-advanced otosclerosis because careful planning of the surgery can positively affect the results. Despite the complexity of the anatomy, the software exactly described the real intrasurgical finding. We think that the use of OTOPLAN might improve the surgical indication.
Topics: Aged; Cochlear Implantation; Cochlear Implants; Humans; Male; Otosclerosis; Software; Stapes Surgery
PubMed: 35193850
DOI: 10.5152/iao.2022.21329 -
The Journal of International Advanced... Nov 2021Acute acoustic trauma is defined as a sudden sensorineural hearing loss that occurs after an exposure to acoustic overstimulation. Increasing the oxygen in perilymph can...
BACKGROUND
Acute acoustic trauma is defined as a sudden sensorineural hearing loss that occurs after an exposure to acoustic overstimulation. Increasing the oxygen in perilymph can be a treatment modality. Our study aims to investigate the influence of normobaric oxygen therapy on the recovery of acute acoustic trauma and to compare it with the hyperbaric oxygen therapy.
METHODS
Three groups of rats (5 rats each) were exposed to white noise for 1 hour. Sensorineural hearing loss was identified using distortion product otoacoustic emission. Subsequently, the first group was treated with hyperbaric oxygen therapy, the second group was treated with normobaric oxygen therapy, and the third group did not receive any treatment and was used as a control group.
RESULTS
There was a statistically significant difference within time for frequencies of 1, 1.5, and 2 kHz, but there was no statistically significant difference between groups. For frequencies of 3, 4, 5, and 6 kHz, there was a statistically significant difference within time and between groups. Between groups, recovery of distortion product otoacoustic emission values in all frequencies was better in the control group by the third, fifth, and seventh days. Comparing the values of hyperbaric oxygen therapy and normobaric oxygen therapy groups, it was observed that by the third day, the hyperbaric oxygen therapy values were better than those of the normobaric oxygen therapy values. However, by the fifth and seventh days, the normobaric oxygen therapy values were better (except at a frequency of 1 kHz).
CONCLUSION
Because there is a high rate of spontaneous recovery, physicians should be more selective to treat patients with oxygen therapies.
Topics: Animals; Hearing Loss, Noise-Induced; Hearing Loss, Sudden; Humans; Hyperbaric Oxygenation; Otoacoustic Emissions, Spontaneous; Oxygen; Rats
PubMed: 35177387
DOI: 10.5152/iao.2021.21019