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Journal articles on the topic 'Antibiotic effects on cochlea'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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1

Moore, David R., Nina J. Rogers, and Stephen J. O'Leary. "Loss of Cochlear Nucleus Neurons following Aminoglycoside Antibiotics or Cochlear Removal." Annals of Otology, Rhinology & Laryngology 107, no. 4 (April 1998): 337–43. http://dx.doi.org/10.1177/000348949810700413.

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This study compared the effects of aminoglycoside ototoxicity and surgical ablation of the cochlea in infancy on the survival of neurons in the rat cochlear nucleus (CN). Ototoxicity was induced by a single, systemic dose of gentamicin sulfate and furosemide on postnatal day 6 (P6), P7, or P10, and assessed by the elevation of auditory brain stem response thresholds, as described in a companion paper. Unilateral cochlear removals were performed under Saffan anesthesia on P6, P9, and P12. Rats were painlessly sacrificed in adulthood, and the formalin-perfused brains and cochleas were embedded in wax, sectioned, and stained. Ototoxic treatment at P6 through P10 did not reduce neuron counts in the CN. Cochlear removal at P6 resulted in a 40% loss of CN neurons, but removal at P12 did not result in CN neuron loss. These data suggest that the critical period for the dependence of CN neurons on afferent input from the cochlea ends at the same time that susceptibility to aminoglycoside ototoxicity begins.

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2

Meli, Damian N., Roney S. Coimbra, Dominik G. Erhart, Gerard Loquet, Caroline L. Bellac, Martin G. Täuber, Ulf Neumann, and Stephen L. Leib. "Doxycycline Reduces Mortality and Injury to the Brain and Cochlea in Experimental Pneumococcal Meningitis." Infection and Immunity 74, no. 7 (July 2006): 3890–96. http://dx.doi.org/10.1128/iai.01949-05.

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ABSTRACT Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 μM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.

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3

Xuan, Weijun, Mingmin Dong, and Minsheng Dong. "Effects of Compound Injection of Pyrola Rotundifolia L and Astragalus Membranaceus Bge on Experimental Guinea Pigs' Gentamicin Ototoxicity." Annals of Otology, Rhinology & Laryngology 104, no. 5 (May 1995): 374–80. http://dx.doi.org/10.1177/000348949510400507.

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In attempting to find drugs effective in preventing and remedying ototoxic injury caused by aminoglycoside antibiotics, we relied on the theory that the induction of ototoxic injury by aminoglycoside antibiotics is related to a decrease of cyclic adenosine monophosphate and RNA content in the cochlea or a dysfunction of the kidney. We selected Pyrola rotundifolia L and Astragalus membranaceus Bge from traditional Chinese herbal medicine, made a compound injection of them, and observed the effect on the pattern of gentamicin ototoxicity in guinea pigs. By electrocochleography and morphology by scanning electron microscopy, the experimental results indicated that the Chinese herbal compound possessed the definite effect of protecting the guinea pig cochlea. The determination of blood urea nitrogen, urinary N-acetyl-d-aminoglucosidase, and urinary protein and observation of renal morphology showed that it also protected the kidney against nephrotoxic nephritis of gentamicin. The conjecture that protection of the kidney by the Chinese herbs may be one of the important factors in preventing ototoxicity supports some explanations of ototoxic mechanisms induced by aminoglycoside antibiotics.

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4

Lee, Sun, Hyun Ju, Jin Choi, Yeji Ahn, Suhun Lee, and Young Seo. "Circulating Serum miRNA-205 as a Diagnostic Biomarker for Ototoxicity in Mice Treated with Aminoglycoside Antibiotics." International Journal of Molecular Sciences 19, no. 9 (September 19, 2018): 2836. http://dx.doi.org/10.3390/ijms19092836.

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Background: To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model. Method: A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs. Results: In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7–14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.

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5

Huseynov, N. M., V. R. Fisenko, and P. R. Aslanov. "INFLUENCE OF OTOTOXIC PHARMACEUTICALS ON BIOELECTRIC RESPONSES IN CEREBRAL CORTEX AND COCHLEA." Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії 20, no. 2 (July 6, 2020): 124–28. http://dx.doi.org/10.31718/2077-1096.20.2.124.

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The article describes the results of the experiment aimed to find out the nature of changes in the excitability of the auditory cortex during prolonged taking of antibiotics, aminoglycosides, diuretics and salicylates. Methodology. The series of experiments was carried out on cats of both sexes weighing 3-3.5 kg, in natural behaviour. Rectangular threshold (1.5-3 V) and supra-threshold (5-7 V) electrical impulses lasting 0.1 ms were applied to the TCR fibres, using single and paired (interstimular intervals of 20-500ms) stimulation of the TCR fibres. As a source of irritating impulses, a multi-channel stimulator "SEN-3201" of the company "Nikon-Kohden" (Japan) was used. For each skeletal interval was carried out on 10 repetitions. The SOFTWARE was registered using the average Det-1100 average from Nikon-Kohden (Japan). The resulting visual control was performed from the screen of the "Disa-Indicator" oscilloscope (Denmark). The maximum level of the intensity value reached 110 dB. Sound signals were transmitted through special high-frequency phones (or speakers) of the GD-4 type, which were in a free state, at a distance of 10 cm from the ear of the test ear. All the studied pharmaceuticals (furosemide, streptomycin, gentamicin, kanamycin, monomycin, tobramycin and amikacin) except acetylsalicylic acid, which was injected intraperitoneally, were administered to cats intramuscularly 2 times a day at intervals of 10-12 hours. Bioelectric reactions of the cortex and cochlea were recorded daily 2-3 hours after the next administration of drugs. Streptomycin, kanamycin and monomycin were used at a dose of 40 mg / kg, which causes inhibition of the cochlea's MIC response (MOI) and auditory nerve PD only with long-term use. Gentamicin, tobramycin and amikacin were administered in a lower (15 mg/kg) dose. Results. Furosemide reduced by 50% the value of the microphone potential recorded during sound stimulation with a frequency of 10 kHz after 4 days, with a frequency of 1 kHz-5 days, with a frequency of 0.5 kHz-6 days from the beginning of use. The most sensitive to furosemide were auditory nerve PD, which occurred during sound stimulation at a frequency of 10 kHz (T50 – 5 days), and less – at a frequency of 0.5 kHz (T50 – 7 days). The cancellation of furosemide was accompanied by the restoration of the value of these bioelectric reactions to the initial level in 5 days. Thus, the data obtained indicate the possibility of a reversible depressing effect of furosemide on the responses of the CGM and the cochlea that occur on sound stimulation. All the studied antibiotics-aminoglycosides had the ability to reduce the value of the testing primary response when paired electrical stimulation of TCR fibres. These changes were observed 2-3 days after the start of the use of antibiotics. Initial changes in the value of MP and PD of the auditory nerve occurred after 12-24 times of drug administration. In this case, a decrease in these potentials by 20-25% was noted. Further use of antibiotics led to an increase in changes in responses registered in the cochlea, with the greatest sensitivity to the effects of drugs were reactions to high-frequency sound stimuli. When analyzing the ability of the studied tools to disrupt the activity of the peripheral fragment of the auditory analyzer, a pattern similar to that for the cerebral cortex was found. Withdrawal of drugs at the stage of initial changes in potentials registered in the cochlea is not accompanied by their recovery for a long (6 weeks) period after stopping the administration of antibiotics. Conclusions. Different rates of formation of damage to interneuronal transmissions were found during long-term use of different antibiotics.

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6

Kim, Ye-Ri, Tae-Jun Kwon, Un-Kyung Kim, In-Kyu Lee, Kyu-Yup Lee, and Jeong-In Baek. "Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea." Antioxidants 10, no. 10 (September 26, 2021): 1526. http://dx.doi.org/10.3390/antiox10101526.

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Drug-induced hearing loss is a major type of acquired sensorineural hearing loss. Cisplatin and aminoglycoside antibiotics have been known to cause ototoxicity, and excessive accumulation of intracellular reactive oxygen species (ROS) are suggested as the common major pathology of cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Fursultiamine, also called thiamine tetrahydrofurfuryl disulfide, is a thiamine disulfide derivative that may have antioxidant effects. To evaluate whether fursultiamine can prevent cisplatin- and kanamycin-induced ototoxicity, we investigated their preventive potential using mouse cochlear explant culture system. Immunofluorescence staining of mouse cochlear hair cells showed that fursultiamine pretreatment reduced cisplatin- and kanamycin-induced damage to both inner and outer hair cells. Fursultiamine attenuated mitochondrial ROS accumulation as evidenced by MitoSOX Red staining and restored mitochondrial membrane potential in a JC-1 assay. In addition, fursultiamine pretreatment reduced active caspase-3 and TUNEL signals after cisplatin or kanamycin treatment, indicating that fursultiamine decreased apoptotic hair cell death. This study is the first to show a protective effect of fursultiamine against cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Our results suggest that fursultiamine could act as an antioxidant and anti-apoptotic agent against mitochondrial oxidative stress.in cochlear hair cells

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7

Yoshida, Naohiro, M. Charles Liberman, M. Christian Brown, and William F. Sewell. "Gentamicin Blocks Both Fast and Slow Effects of Olivocochlear Activation in Anesthetized Guinea Pigs." Journal of Neurophysiology 82, no. 6 (December 1, 1999): 3168–74. http://dx.doi.org/10.1152/jn.1999.82.6.3168.

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The medial olivocochlear (MOC) efferent system, which innervates cochlear outer hair cells, suppresses cochlear responses. MOC-mediated suppression includes both slow and fast components, with time courses differing by three orders of magnitude. Pharmacological studies in anesthetized guinea pigs suggest that both slow and fast effects on cochlear responses require an initial acetylcholine activation of α-9 nicotinic receptors on outer hair cells and that slow effects require additional intracellular events downstream from those mediating fast effects. Gentamicin, an aminoglycoside antibiotic, has been reported to block fast effects of sound-evoked OC activation following intramuscular injection in unanesthetized guinea pigs, without changing slow effects. In the present study, we show that electrically evoked fast and slow effects in the anesthetized guinea pig are both blocked by either intramuscular or intracochlear gentamicin, with similar time courses and/or dose-response curves. We suggest that sound-evoked slow effects in unanesthetized animals are fundamentally different from electrically evoked slow effects in anesthetized animals, and that the former may arise from effects of the lateral OC system.

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8

Nakagawa, T., S. Kakehata, N. Akaike, S. Komune, T. Takasaka, and T. Uemura. "Effects of Ca2+ antagonists and aminoglycoside antibiotics on Ca2+ current in isolated outer hair cells of guinea pig cochlea." Brain Research 580, no. 1-2 (May 1992): 345–47. http://dx.doi.org/10.1016/0006-8993(92)90966-d.

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9

O’Sullivan, Mary E., Yohan Song, Robert Greenhouse, Randy Lin, Adela Perez, Patrick J. Atkinson, Jacob P. MacDonald, et al. "Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes." Proceedings of the National Academy of Sciences 117, no. 51 (December 7, 2020): 32423–32. http://dx.doi.org/10.1073/pnas.2013065117.

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Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin C-subtypes and several impurities of various ranges of nonexact concentrations. We developed a purification strategy enabling assaying of individual C-subtypes and impurities for ototoxicity and antimicrobial activity. We found that C-subtypes displayed broad and potent in vitro antimicrobial activities comparable to the hospital gentamicin mixture. In contrast, they showed different degrees of ototoxicity in cochlear explants, with gentamicin C2b being the least and gentamicin C2 the most ototoxic. Structure–activity relationships identified sites in the C4′-C6′ region on ring I that reduced ototoxicity while preserving antimicrobial activity, thus identifying targets for future drug design and mechanisms for hair cell toxicity. Structure–activity relationship data suggested and electrophysiological data showed that the C-subtypes both bind and permeate the hair cell mechanotransducer channel, with the stronger the binding the less ototoxic the compound. Finally, both individual and reformulated mixtures of C-subtypes demonstrated decreased ototoxicity while maintaining antimicrobial activity, thereby serving as a proof-of-concept of drug reformulation to minimizing ototoxicity of gentamicin in patients.

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10

Beitel, Ralph E., Russell L. Snyder, Christoph E. Schreiner, Marcia W. Raggio, and Patricia A. Leake. "Electrical Cochlear Stimulation in the Deaf Cat: Comparisons Between Psychophysical and Central Auditory Neuronal Thresholds." Journal of Neurophysiology 83, no. 4 (April 1, 2000): 2145–62. http://dx.doi.org/10.1152/jn.2000.83.4.2145.

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Cochlear prostheses for electrical stimulation of the auditory nerve (“electrical hearing”) can provide auditory capacity for profoundly deaf adults and children, including in many cases a restored ability to perceive speech without visual cues. A fundamental challenge in auditory neuroscience is to understand the neural and perceptual mechanisms that make rehabilitation of hearing possible in these deaf humans. We have developed a feline behavioral model that allows us to study behavioral and physiological variables in the same deaf animals. Cats deafened by injection of ototoxic antibiotics were implanted with either a monopolar round window electrode or a multichannel scala tympani electrode array. To evaluate the effects of perceptually significant electrical stimulation of the auditory nerve on the central auditory system, an animal was trained to avoid a mild electrocutaneous shock when biphasic current pulses (0.2 ms/phase) were delivered to its implanted cochlea. Psychophysical detection thresholds and electrical auditory brain stem response (EABR) thresholds were estimated in each cat. At the conclusion of behavioral testing, acute physiological experiments were conducted, and threshold responses were recorded for single neurons and multineuronal clusters in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (A1). Behavioral and neurophysiological thresholds were evaluated with reference to cochlear histopathology in the same deaf cats. The results of the present study include: 1) in the cats implanted with a scala tympani electrode array, the lowest ICC and A1 neural thresholds were virtually identical to the behavioral thresholds for intracochlear bipolar stimulation; 2) behavioral thresholds were lower than ICC and A1 neural thresholds in each of the cats implanted with a monopolar round window electrode; 3) EABR thresholds were higher than behavioral thresholds in all of the cats (mean difference = 6.5 dB); and 4) the cumulative number of action potentials for a sample of ICC neurons increased monotonically as a function of the amplitude and the number of stimulating biphasic pulses. This physiological result suggests that the output from the ICC may be integrated spatially across neurons and temporally integrated across pulses when the auditory nerve array is stimulated with a train of biphasic current pulses. Because behavioral thresholds were lower and reaction times were faster at a pulse rate of 30 pps compared with a pulse rate of 2 pps, spatial-temporal integration in the central auditory system was presumably reflected in psychophysical performance.

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11

Kalkandelen, S., E. Selimoğlu, F. Erdoğan, H. Üçüncü, and E. Altaş. "Comparative Cochlear Toxicities of Streptomycin, Gentamicin, Amikacin and Netilmicin in Guinea-Pigs." Journal of International Medical Research 30, no. 4 (August 2002): 406–12. http://dx.doi.org/10.1177/147323000203000407.

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All the aminoglycoside antibiotics now in clinical use are ototoxic. This study was designed to compare the toxic effects of four aminoglycoside antibiotics, streptomycin, gentamicin, amikacin and netilmicin, administered to guinea-pigs systemically (at respective doses of 125 mg/kg, 50 mg/kg, 150 mg/kg or 37.5 mg/kg, twice daily for 1 week) or topically via the transtympanic route (0.25 ml/kg in 4% saline, twice daily for 1 week). Chosen doses were 10–20 times higher than the recommended human dosage. Cochlear damage was observed in all animals that were given systemic and local aminoglycosides. The severity of the cochlear damage was in the order gentamicin, amikacin, streptomycin, netilmicin, with gentamicin being the most toxic. No statistically significant difference between the severity of cochlear damage resulting from the systemic and topical applications was detected.

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12

Högen, Tobias, Cornelia Demel, Armin Giese, Barbara Angele, Hans-Walter Pfister, Uwe Koedel, and Matthias Klein. "AdjunctiveN-Acetyl-l-Cysteine in Treatment of Murine Pneumococcal Meningitis." Antimicrobial Agents and Chemotherapy 57, no. 10 (July 22, 2013): 4825–30. http://dx.doi.org/10.1128/aac.00148-13.

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ABSTRACTDespite antibiotic therapy, acute and long-term complications are still frequent in pneumococcal meningitis. One important trigger of these complications is oxidative stress, and adjunctive antioxidant treatment withN-acetyl-l-cysteine was suggested to be protective in experimental pneumococcal meningitis. However, studies of effects on neurological long-term sequelae are limited. Here, we investigated the impact of adjunctiveN-acetyl-l-cysteine on long-term neurological deficits in a mouse model of meningitis. C57BL/6 mice were intracisternally infected withStreptococcus pneumoniae. Eighteen hours after infection, mice were treated with a combination of ceftriaxone and placebo or ceftriaxone andN-acetyl-l-cysteine, respectively. Two weeks after infection, neurologic deficits were assessed using a clinical score, an open field test (explorative activity), a t-maze test (memory function), and auditory brain stem responses (hearing loss). Furthermore, cochlear histomorphological correlates of hearing loss were assessed. AdjunctiveN-acetyl-l-cysteine reduced hearing loss after pneumococcal meningitis, but the effect was minor. There was no significant benefit of adjunctiveN-acetyl-l-cysteine treatment in regard to other long-term complications of pneumococcal meningitis. Cochlear morphological correlates of meningitis-associated hearing loss were not reduced by adjunctiveN-acetyl-l-cysteine. In conclusion, adjunctive therapy withN-acetyl-l-cysteine at a dosage of 300 mg/kg of body weight intraperitoneally for 4 days reduced hearing loss but not other neurologic deficits after pneumococcal meningitis in mice. These results make a clinical therapeutic benefit ofN-acetyl-l-cysteine in the treatment of patients with pneumococcal meningitis questionable.

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13

Dong, Wei, and Nigel P. Cooper. "An experimental study into the acousto-mechanical effects of invading the cochlea." Journal of The Royal Society Interface 3, no. 9 (March 2, 2006): 561–71. http://dx.doi.org/10.1098/rsif.2006.0117.

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The active and nonlinear mechanical processing of sound that takes place in the mammalian cochlea is fundamental to our sense of hearing. We have investigated the effects of opening the cochlea in order to make experimental observations of this processing. Using an optically transparent window that permits laser interferometric access to the apical turn of the guinea-pig cochlea, we show that the acousto-mechanical transfer functions of the sealed (i.e. near intact) cochlea are considerably simpler than those of the unsealed cochlea. Comparison of our results with those of others suggests that most previous investigations of apical cochlear mechanics have been made under unsealed conditions, and are therefore likely to have misrepresented the filtering of low-frequency sounds in the cochlea. The mechanical filtering that is apparent in the apical turns of sealed cochleae also differs from the filtering seen in individual auditory nerve fibres with similar characteristic frequencies. As previous studies have shown the neural and mechanical tuning of the basal cochlea to be almost identical, we conclude that the strategies used to process low frequency sounds in the apical turns of the cochlea might differ fundamentally from those used to process high frequency sounds in the basal turns.

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14

DiSogra, Robert. "Common Aminoglycosides and Platinum-Based Ototoxic Drugs: Cochlear/Vestibular Side Effects and Incidence." Seminars in Hearing 40, no. 02 (April 26, 2019): 104–7. http://dx.doi.org/10.1055/s-0039-1684040.

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AbstractThis is a reference chart that identifies 16 aminoglycoside antibiotics and platinum based drugs that could be cochleotoxic, vestibulotoxic or both. Using the most currently available data from published research from the National Library of Medicine's PubMed data base, incidence figures and risk factors are included in the chart along with the potential of permanence of reversibility of the impairment.

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15

Jäger, W., S. M. Khanna, B. Flock, and Å. Flock. "Micromechanical effects in the cochlea of tetracaine." Hearing Research 134, no. 1-2 (August 1999): 179–85. http://dx.doi.org/10.1016/s0378-5955(99)00083-0.

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16

Satar, B??lent, Yal??in ??zkaptan, H. Sel??uk S??r??c??, and Hakan ??zt??rk. "Ultrastructural Effects of Hypercholesterolemia on the Cochlea." Otology & Neurotology 22, no. 6 (November 2001): 786–89. http://dx.doi.org/10.1097/00129492-200111000-00012.

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17

Ito, Hisako. "Effects of Circulatory Disturbance on the Cochlea." ORL 53, no. 5 (1991): 265–69. http://dx.doi.org/10.1159/000276226.

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18

Cunha, Burke A. "ANTIBIOTIC SIDE EFFECTS." Medical Clinics of North America 85, no. 1 (January 2001): 149–85. http://dx.doi.org/10.1016/s0025-7125(05)70309-6.

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19

Gleckman, Richard A., and John S. Czachor. "Antibiotic Side Effects." Seminars in Respiratory and Critical Care Medicine 21, no. 1 (2000): 0061–70. http://dx.doi.org/10.1055/s-2000-9928.

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20

Cheetham, D. J. "Antibiotic side effects." British Dental Journal 168, no. 7 (April 1990): 277. http://dx.doi.org/10.1038/sj.bdj.4807176.

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21

Shaw, N. "Antibiotic side effects'." British Dental Journal 168, no. 9 (May 1990): 349. http://dx.doi.org/10.1038/sj.bdj.4807200.

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22

NAMBA, Gen, and Yasuya NOMURA. "Morphological Effects of Laser Irradiation on the Cochlea." Showa University Journal of Medical Sciences 9, no. 1 (1997): 25–32. http://dx.doi.org/10.15369/sujms1989.9.25.

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23

Streicher, B., and R. Lang-Roth. "C082 Effects of early cochlea implantation on reading." International Journal of Pediatric Otorhinolaryngology 75 (May 2011): 48. http://dx.doi.org/10.1016/s0165-5876(11)70250-6.

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24

Schacht, Jochen. "Aminoglycoside Ototoxicity: Prevention in Sight?" Otolaryngology–Head and Neck Surgery 118, no. 5 (May 1998): 674–77. http://dx.doi.org/10.1177/019459989811800518.

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Despite the development of new antibiotics, the aminoglycosides are still indispensable in the treatment of life-threatening diseases. Worldwide they are the most commonly used antibiotics, and their use is expected to increase in the wake of the rising incidence of tuberculosis. The most prominent side effects of aminoglycoside treatment—cochlear, vestibular, and renal impairment—are a limiting factor in the utility of these drugs. A novel mechanism of gentamicin ototoxicity is based on observations of iron chelation and free radical formation. Predictions from this mechanism have led to successful therapeutic prevention of ototoxicity by use of iron chelators and radical scavengers in guinea pigs. The drugs used for this interventive treatment affect neither serum levels of gentamicin nor its antibacterial efficacy. Because these drugs are in clinical use, the suggested protective treatment should lend itself to clinical trials. (Otolaryngol Head Neck Surg 1998;118:674-7.)

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25

Macri, John R., and Richard A. Chole. "Bone Erosion in Experimental Cholesteatoma — The Effects of Implanted Barriers." Otolaryngology–Head and Neck Surgery 93, no. 1 (February 1985): 3–17. http://dx.doi.org/10.1177/019459988509300102.

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Mongolian gerbils and man are the only animals known to spontaneously develop bone-eroding aural cholesteatoma. The pathophysiology of bone erosion in cholesteatoma is controversial. The majority of investigators believe that direct contact between cholesteatoma and bone is necessary for erosion to occur. We implanted glass, Silastic, and micropore barriers in the middle ear between the advancing cholesteatoma and cochlea in 50 Mongolian gerbils. The barriers prevented direct contact of cholesteatoma and cochlea but did not inhibit bone erosion. We conclude that transmitted pressure may be responsible for bone erosion in aural cholesteatoma in gerbils.

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26

Hershberg, Ruth. "Antibiotic-Independent Adaptive Effects of Antibiotic Resistance Mutations." Trends in Genetics 33, no. 8 (August 2017): 521–28. http://dx.doi.org/10.1016/j.tig.2017.05.003.

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27

Spiess, Adam C., Hainan Lang, Bradley A. Schulte, S. S. Spicer, and Richard A. Schmiedt. "Effects of Gap Junction Uncoupling in the Gerbil Cochlea." Laryngoscope 112, no. 9 (September 2002): 1635–41. http://dx.doi.org/10.1097/00005537-200209000-00020.

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28

Cho, Kyoung-rai, and Chan Choi. "R074: Effects of Lidocaine Perfusion in Guinea Pig Cochlea." Otolaryngology–Head and Neck Surgery 137, no. 2_suppl (August 2007): P175. http://dx.doi.org/10.1016/j.otohns.2007.06.409.

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29

Jackler, Robert K., Patricia A. Leake, and William S. McKerrow. "Cochlear Implant Revision: Effects of Reimplantation on the Cochlea." Annals of Otology, Rhinology & Laryngology 98, no. 10 (October 1989): 813–20. http://dx.doi.org/10.1177/000348948909801012.

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The removal of an indwelling cochlear implant electrode followed by reinsertion of a new device has been a maneuver of uncertain cosequences to the cochlea and its surviving neural population. The present study was conducted in an attempt to elucidate the factors at determine whether a reimplantation procedure will be successful. Cochlear implantation followed by explanation and subsequent implantation was performed in eight adult cats. Evaluation of cochlear histopathology suggested a significant increase in electrode insertion trauma when there was proliferation of granulation tissue in the round window area and scala tympani. In other cases, atraumatic insertion was achieved without apparent injury to the cochlea. The results of a survey of cochlear implant manufacturers and surgeons indicate that electrode replacement can usually be accomplished without adverse effects. Difficulties have been encountered, however, in moving implants with protuberant electrodes and when reimplantation was attempted on a delayed basis following explanation.

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Fu, Mingyu, Mengzi Chen, Xiao Yan, Xueying Yang, Jinfang Xiao, and Jie Tang. "The Effects of Urethane on Rat Outer Hair Cells." Neural Plasticity 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/3512098.

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The cochlea converts sound vibration into electrical impulses and amplifies the low-level sound signal. Urethane, a widely used anesthetic in animal research, has been shown to reduce the neural responses to auditory stimuli. However, the effects of urethane on cochlea, especially on the function of outer hair cells, remain largely unknown. In the present study, we compared the cochlear microphonic responses between awake and urethane-anesthetized rats. The results revealed that the amplitude of the cochlear microphonic was decreased by urethane, resulting in an increase in the threshold at all of the sound frequencies examined. To deduce the possible mechanism underlying the urethane-induced decrease in cochlear sensitivity, we examined the electrical response properties of isolated outer hair cells using whole-cell patch-clamp recording. We found that urethane hyperpolarizes the outer hair cell membrane potential in a dose-dependent manner and elicits larger outward current. This urethane-induced outward current was blocked by strychnine, an antagonist of theα9 subunit of the nicotinic acetylcholine receptor. Meanwhile, the function of the outer hair cell motor protein, prestin, was not affected. These results suggest that urethane anesthesia is expected to decrease the responses of outer hair cells, whereas the frequency selectivity of cochlea remains unchanged.

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Perde-Schrepler, Maria, Adrian Florea, Ioana Brie, Piroska Virag, Eva Fischer-Fodor, Angela Vâlcan, Eugen Gurzău, Cosmin Lisencu, and Alma Maniu. "Size-Dependent Cytotoxicity and Genotoxicity of Silver Nanoparticles in Cochlear Cells In Vitro." Journal of Nanomaterials 2019 (February 26, 2019): 1–12. http://dx.doi.org/10.1155/2019/6090259.

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Silver nanoparticles (AgNPs) have been proven to have potent antibacterial properties, offering an attractive alternative to antibiotics in the treatment of several infections such as otitis media. Concerns have been raised though regarding their toxicity. There are few data regarding the toxic effects of AgNPs in cochlear cells. The aim of our study was to evaluate the effects of AgNPs of four sizes as a function of their size on HEI-OC1 cochlear cells and on HaCaT keratinocytes. The cells were treated with different concentrations of AgNPs. We evaluated silver uptake by atomic absorption spectroscopy and transmission electron microscopy (TEM), cytotoxicity with the alamarBlue test, ROS production with 2′,7′-dichloro-dihydro-fluorescein diacetate, and genotoxicity with the comet assay. Silver intracellular concentration increased proportionally with the incubation time and the size of the NPs. Silver uptake was higher in HEI-OC1 cells compared to HaCaT. While after 4 h exposure, only the 50 nm NPs were observed in both cell lines and only the 5 nm NPs were observed in the HaCaT cells, after 24 h, nanoparticles of all sizes could be visualized in both cell lines. The cells showed signs of distress: vacuolizations, autophagosomes, signs of apoptosis, or cellular debris. AgNPs of all sizes reduced viability proportionally with the concentration, HEI-OC1 cells being more affected. The toxicity of AgNPs decreased with the nanoparticle size, and ROS production was dose and size dependent, mainly in the cochlear cells. Genotoxicity assessed by comet assay revealed a higher level of DNA lesions in HEI-OC1 cells after treatment with small-sized AgNPs. The perspective of using AgNPs in the treatment of otitis media, although very attractive, must be regarded with caution: cochlear cells proved to be more sensitive to the toxic effect of AgNPs compared to other cell lines. Potential treatments must be tailored specifically, choosing NPs with minimum toxicity towards auditory cells.

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Cai, Hongxue, Daphne Manoussaki, and Richard Chadwick. "Effects of coiling on the micromechanics of the mammalian cochlea." Journal of The Royal Society Interface 2, no. 4 (June 16, 2005): 341–48. http://dx.doi.org/10.1098/rsif.2005.0049.

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The cochlea transduces sound-induced vibrations in the inner ear into electrical signals in the auditory nerve via complex fluid–structure interactions. The mammalian cochlea is a spiral-shaped organ, which is often uncoiled for cochlear modelling. In those few studies where coiling has been considered, the cochlear partition was often reduced to the basilar membrane only. Here, we extend our recently developed hybrid analytical/numerical micromechanics model to include curvature effects, which were previously ignored. We also use a realistic cross-section geometry, including the tectorial membrane and cellular structures of the organ of Corti, to model the apical and basal regions of a guinea-pig cochlea. We formulate the governing equations of the fluid and solid domains in a curvilinear coordinate system. The WKB perturbation method is used to treat the propagation of travelling waves along the coiled cochlear duct, and the O (1) system of the governing equations is solved in the transverse plane using finite-element analysis. We find that the curvature of the cochlear geometry has an important functional significance; at the apex, it greatly increases the shear gain of the cochlear partition, which is a measure of the bending efficiency of the outer hair cell stereocilia.

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da Silva, Julierme G., Miguel A. Hyppolito, José Antônio A. de Oliveira, Alexandre P. Corrado, Izabel Y. Ito, and Ivone Carvalho. "Aminoglycoside antibiotic derivatives: Preparation and evaluation of toxicity on cochlea and vestibular tissues and antimicrobial activity." Bioorganic & Medicinal Chemistry 15, no. 11 (June 1, 2007): 3624–34. http://dx.doi.org/10.1016/j.bmc.2007.03.056.

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34

Darrow, David H., Elizabeth M. Keithley, and Jeffrey P. Harris. "Effects of Bacterial Endotoxin Applied to the Guinea Pig Cochlea." Laryngoscope 102, no. 6 (June 1992): 683–88. http://dx.doi.org/10.1288/00005537-199206000-00015.

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Meixner, Kathleen E., Patrick J. Antonelli, and Joseph E. Dohar. "The Effects of Kanamycin Injection into the Fetal Lamb Cochlea." Ear, Nose & Throat Journal 78, no. 3 (March 1999): 196–204. http://dx.doi.org/10.1177/014556139907800313.

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36

Shirane, Makoto, and Robert V. Harrison. "The Effects of Deferoxamine Mesylate and Hypoxia on the Cochlea." Acta Oto-Laryngologica 104, no. 1-2 (January 1987): 99–107. http://dx.doi.org/10.3109/00016488709109053.

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Ulfendahl, Mats, Shyam M. Khanna, and Ake Flock. "Effects of Caffeine on the Micromechanics of the Isolated Cochlea." Acta Oto-Laryngologica 108, sup467 (January 1989): 221–28. http://dx.doi.org/10.3109/00016488909138341.

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Manoussaki, Daphne, and Richard S. Chadwick. "Effects of Geometry on Fluid Loading in a Coiled Cochlea." SIAM Journal on Applied Mathematics 61, no. 2 (January 2000): 369–86. http://dx.doi.org/10.1137/s0036139999358404.

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Ishida, Akira, Takahisa Sugisawa, and Kohtaroh Yamamura. "Effects of High-Frequency Sound on the Guinea Pig Cochlea." ORL 55, no. 6 (1993): 332–36. http://dx.doi.org/10.1159/000276450.

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d'Aldin, Christine, Jean-Luc Puel, Régine Leducq, Olivier Crambes, Michel Eybalin, and Rémy Pujol. "Effects of a dopaminergic agonist in the guinea pig cochlea." Hearing Research 90, no. 1-2 (October 1995): 202–11. http://dx.doi.org/10.1016/0378-5955(95)00167-5.

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41

Murphy, DM, IA Forrest, D. Curran, and C. Ward. "Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?" Expert Opinion on Investigational Drugs 19, no. 3 (February 14, 2010): 401–14. http://dx.doi.org/10.1517/13543781003636480.

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Pietola, Laura. "Effects of p27Kip1- and p53- shRNAs on kanamycin damaged mouse cochlea." World Journal of Otorhinolaryngology 2, no. 1 (2012): 1. http://dx.doi.org/10.5319/wjo.v2.i1.1.

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Ahroon, William A., and Roger P. Hamernik. "The effects of interrupted noise exposures on the noise-damaged cochlea." Hearing Research 143, no. 1-2 (May 2000): 103–9. http://dx.doi.org/10.1016/s0378-5955(00)00030-7.

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Farhadi, M., A. Asghari, M. Jalessi, and H. Emamdjomeh. "F049 Effects of dexamethasone loaded silicone implant in guinea pig cochlea." International Journal of Pediatric Otorhinolaryngology 75 (May 2011): 92. http://dx.doi.org/10.1016/s0165-5876(11)70472-4.

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Ishimoto, Shin-ichi, Kohei Kawamoto, Timo Stöver, Sho Kanzaki, Tatsuya Yamasoba, and Yehoash Raphael. "A Glucocorticoid Reduces Adverse Effects of Adenovirus Vectors in the Cochlea." Audiology and Neurotology 8, no. 2 (2003): 70–79. http://dx.doi.org/10.1159/000069000.

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Bartolami, Sylvain, Myriam Planche, and Rémy Pujol. "Effects of ototoxins on quinuclidinyl benzylate binding in the rat cochlea." Neuroscience Letters 174, no. 2 (June 1994): 169–72. http://dx.doi.org/10.1016/0304-3940(94)90013-2.

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Guo, Chunxiao, and Adrian Gombart. "The Antibiotic Effects of Vitamin D." Endocrine, Metabolic & Immune Disorders-Drug Targets 14, no. 4 (November 12, 2014): 255–66. http://dx.doi.org/10.2174/1871530314666140709085159.

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Odenholt, Inga. "Pharmacodynamic effects of subinhibitory antibiotic concentrations." International Journal of Antimicrobial Agents 17, no. 1 (January 2001): 1–8. http://dx.doi.org/10.1016/s0924-8579(00)00243-0.

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Gulis, V. I., and A. I. Stephanovich. "Antibiotic effects of some aquatic hyphomycetes." Mycological Research 103, no. 1 (January 1999): 111–15. http://dx.doi.org/10.1017/s095375629800690x.

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Buczek, Krzysztof, and Mateusz Marć. "Bacterial antibiotic resistance - reasons and effects." Annales UMCS, Medicina Veterinaria 64, no. 3 (January 1, 2009): 1–8. http://dx.doi.org/10.2478/v10082-009-0006-5.

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