scholarly journals Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs

2018 ◽  
Vol 23 (4) ◽  
pp. 245-257 ◽  
Author(s):  
Alec N. Salt ◽  
Jared J. Hartsock ◽  
Fabrice Piu ◽  
Jennifer Hou

Dexamethasone phosphate is widely used for intratympanic therapy in humans. We assessed the pharmacokinetics of dexamethasone entry into perilymph when administered as a dexamethasone phosphate solution or as a micronized dexamethasone suspension, with and without inclusion of poloxamer gel in the medium. After a 1-h application to guinea pigs, 10 independent samples of perilymph were collected from the lateral semicircular canal of each animal, allowing entry at the round window and stapes to be independently assessed. Both forms of dexamethasone entered the perilymph predominantly at the round window (73%), with a lower proportion entering at the stapes (22%). When normalized by applied concentration, dexamethasone phosphate was found to enter perilymph far more slowly than dexamethasone, in accordance with its calculated lipid solubility and polar surface area properties. Dexamethasone phosphate therefore has a problematic combination of kinetic properties when used for local therapy of the ear. It is relatively impermeable and enters perilymph only slowly from the middle ear. It is then metabolized in the ear to dexamethasone, which is more permeable through tissue boundaries and is rapidly lost from perilymph. Understanding the influence of molecular properties on the distribution of drugs in perilymph provides a new level of understanding which may help optimize drug therapies of the ear.

1989 ◽  
Vol 100 (2) ◽  
pp. 134-136 ◽  
Author(s):  
Roger R. Marsh ◽  
Lawrence W.C. Tom

Neither otomycoses nor defects of the tympanic membrane are rare. In cases of fungal infection when the tympanic membrane is not intact, the possibility exists that antimycotic medication could enter the middle ear and diffuse into the cochlea via the round window. Five antimycotic preparations were tested for acute ototoxic potential in guinea pigs. Those containing acetic acid or propylene glycol caused appreciable elevation of brainstem response thresholds, while little or no impairment resulted from tolnaftate or clotrimazole solutions in polyethylene glycol 400.


Sensors ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 946
Author(s):  
Dong Ho Shin

This report describes the design of a new piezoelectric transducer for round window (RW)-driven middle ear implants. The transducer consists of a piezoelectric element, gold-coated copper bellows, silicone elastomer (polydimethylsiloxane, PDMS), metal cylinder (tungsten), and titanium housing. The piezoelectric element is fixed to the titanium housing and mechanical resonance is generated by the interaction of the bellows, PDMS, and tungsten cylinder. The dimensions of PDMS and the tungsten cylinder with output characteristics suitable for compensation of sensorineural hearing loss were derived by mechanical vibrational analysis (equivalent mechanical model and finite element analysis (FEA)). Based on the results of FEA, the RW piezoelectric transducer was implemented, and bench tests were performed under no-load conditions to confirm the output characteristics. The transducer generates an average displacement of 219.6 nm in the flat band (0.1–1 kHz); the resonance frequency is 2.3 kHz. To evaluate the output characteristics, the response was compared to that of an earlier transducer. When driven by the same voltage (6 Vp), the flat band displacement averaged 30 nm larger than that of the other transducer, and no anti-resonance was noted. Therefore, we expect that the new transducer can serve as an output device for hearing aids, and that it will improve speech recognition and treat high-frequency sensorineural hearing loss more effectively.


1988 ◽  
Vol 105 (sup457) ◽  
pp. 139-143 ◽  
Author(s):  
E. M. Keithley ◽  
A. F. Ryan ◽  
J. P. Harris

1979 ◽  
Vol 88 (3) ◽  
pp. 368-376 ◽  
Author(s):  
A. Axelsson ◽  
J. Miller ◽  
M. Silverman

Acute middle ear (ME) and inner ear changes following brief unilateral phasic ME pressure changes (up to ± 6000/mm H2O) were studied in the guinea pig. Middle ear findings included perforation of the tympanic membrane, serous and serosanguinous exudate and hemorrhage of tympanic membrane and periosteal vessels. Changes were related to magnitude of applied pressure. Perforation and hemorrhage were more commonly seen with negative rather than positive pressure. Air bubbles behind the round window were seen with positive pressures. Occasional distortion, but never perforation of the round window, was noted. Hemorrhage of the scala tympani was observed with both positive and negative pressures; scala vestibuli hemorrhage was found with negative ME pressure. In some instances pressure direction and magnitude related changes were seen in the contralateral ear.


2003 ◽  
Vol 117 (9) ◽  
pp. 700-703 ◽  
Author(s):  
Recep Yagiz ◽  
Abdullah Tas ◽  
Cem Uzun ◽  
Mustafa Kemal Adali ◽  
Muhsin Koten ◽  
...  

The possible cochlear toxicity of topically applied povidone-iodine solution was investigated in guinea pigs by measuring transiently evoked otoacoustic emissions (TEOAEs). Seven adult pigmented guinea pigs (14 ears) with a normal acoustic pinna reflex were used. After the baseline TEOAE measurements, 0.1mL of povidone-iodine solution was applied transtympanically into the middle ear in the study group. Saline solution and gentamicin were used as negative and positive control, respectively. TEOAE measurements were repeated on the 10th day, and four weeks after the first application. Tympanometric measurements were also carried out for both ears of all animals at the end of the study. Responses in all ears, which had povidone-iodine applied to them, disappeared in a way similar to those recorded in gentamicin-treated ears. Tympanometric measurements at the end of the study showed ’type A’ tympanograms in all ears of all animals. The present study showed that povidone-iodine could have a cochleotoxic effect in guinea pigs. A study in humans with TEOAE before and after middle-ear surgery, where povidone-iodine can reach into the middle-ear cavity, may be useful for evaluating this result for clinical practice.


1997 ◽  
Vol 78 (4) ◽  
pp. 1826-1836 ◽  
Author(s):  
Deise Lima da Costa ◽  
Anne Chibois ◽  
Jean-Paul Erre ◽  
Christophe Blanchet ◽  
RENAUD CHARLET de Sauvage ◽  
...  

Lima da Costa, Deise, Anne Chibois, Jean-Paul Erre, Christophe Blanchet, Renaud Charlet de Sauvage, and Jean-Marie Aran. Fast, slow, and steady-state effects of contralateral acoustic activation of the medial olivocochlear efferent system in awake guinea pigs: action of gentamicin. J. Neurophysiol. 78: 1826–1836, 1997. The function of the medial olivocochlear efferent system was observed in awake guinea pigs by recording, in the absence of ipsilateral external acoustic stimulation, the ensemble background activity (EBA) of the VIIIth nerve from an electrode chronically implanted on the round window of one ear. The EBA was measured by calculating the power value of the round window signal in the 0.5- to 2.5-kHz band after digital or analog (active) filtering. This EBA was compared with and without the addition of a low-level broadband noise to the opposite ear. The contralateral broadband noise (CLBN, 55 dB SPL) induced, via the efferent system, a decrease (suppression) of this EBA. With the use of noise bursts of different durations, two components in this suppression could be observed. After the onset of a 1-s CLBN, the power value of the EBA decreased rapidly by 38.0 ± 4.2% (mean ± SD, n = 3), with a latency of <10 ms and a decay time constant of 13.1 ± 1.0 ms (fast effect). At the offset of the 1-s CLBN, EBA came back to prestimulation values with a similar latency and a time constant of 15.5 ± 2.9 ms. During longer CLBN stimulation (≥1 min), EBA presented, after the fast decrease, an additional, slower decrease of 15.6 ± 3.1%, with a delay of 9.8 ± 1.3 s and a decay time constant of 16.1 ± 5.0 s ( n = 12, slow effect), and then remained remarkably constant for as long as observed, i.e., >2 h (steady state). The average global suppression was thus up to 47.8 ± 5.8% of the basal, pre-CLBN-stimulation EBA value. At the offset of the CLBN, EBA returned to pre-CLBN level with fast and slow phases, with, for the slow phase, no delay and a time constant of 32.1 ± 8.1 s. Fast and slow changes in EBA power values were observed after a single injection of gentamicin (GM) at different doses (150, 200, and 250 mg/kg). At 150 and 200 mg/kg, GM progressively and reversibly blocked the rapid effect, but the slow component of the efferent medial suppression remained remarkably unchanged. However, at higher doses both the fast and slow suppressions were totally yet still reversibly blocked. These observations indicate that the medial olivocochlear efferent system exerts sustained influences on outer hair cells and that this effect develops in two different steps that may have different basic cellular mechanisms.


2010 ◽  
Vol 263 (1-2) ◽  
pp. 251
Author(s):  
N. Julian Holland ◽  
Kanthaiah Koka ◽  
J. Eric Lupo ◽  
Daniel J. Tollin ◽  
Herman A. Jenkins

1991 ◽  
Vol 101 (3) ◽  
pp. 271???275 ◽  
Author(s):  
Antonino Catanzaro ◽  
Allen Ryan ◽  
Sharon Batcher ◽  
Stephen I. Wasserman
Keyword(s):  

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