Pigmented Guinea Pigs Research Articles

Immunoreactivities for glutathione S-transferases and glutathione peroxidase in the lateral wall of pigmented and albino guinea pig cochlea

Dark-skinned people are known to be more tolerant of ototraumatic noise than are light-skinned people, and pigmented animals are more tolerant of ototraumatic noise and aminoglycoside ototoxicity than are albino animals. Such tolerance may be dependent on the local ability of detoxification and antioxidant enzymes, including glutathione S-transferase (GST) and glutathione peroxidase (GSPx). In the present study, we examined the difference in GST/GSPx expression in the lateral wall of the cochlea between pigmented and albino guinea pigs. Eight-week-old male pigmented and albino guinea pigs were killed by transcardiac perfusion with 2% paraformaldehyde. The cochlear ducts were isolated, further fixed with 4% paraformaldehyde, decalcified, and then embedded in paraffin. Sections prepared at 5-microm thickness were incubated with anti-GST-alpha,-mu,-pi, or anti-GSPx antibody, reacted with Alexa Fluorconjugated secondary antibody, and examined under a Carl Zeiss Axioskop 2 plus fluorescence microscope. The cochlea ducts were also subjected to immunoelectron microscopy for GST-pi by the postembedment method. The stria vascularis of pigmented guinea pigs was strongly immunoreactive for GST-alpha,-mu,-pi, and GSPx, whereas no or only weak immunoreactivities were seen in the stria vascularis of albino guinea pigs. The spiral ligament showed positive but different immunoreactivities for these enzymes between the strains. Double-stained immunofluorescence micrographs for GST-pi and GSPx showed a close resemblance of localization between the two enzymes in both pigmented and albino guinea pigs. At the ultrastructural level, immunoreactivity for GST-pi was localized preferentially in the melanin cells of pigmented guinea pigs. These results suggest that correlation between pigmentation and inner ear susceptibility is, at least partially, attributed to the different distribution of GST/GSPx in the stria vascularis.

Guinea Pig Ototoxicity With Hydrocodone and Acetaminophen

Problem Human case reports have been published demonstrating a rapidly progressive sensorineural hearing loss associated with overuse or abuse of acetaminophen/hydrocodone. We hypothesized that hearing loss would result in the guinea pig model if given high, chronic doses of this drug. Methods Sixty female, pigmented guinea pigs were randomly assigned to a control, acetaminophen, hydrocodone, or acetaminophen/hydrocodone group. All guinea pigs were tested with baseline ABRs on day 0, and post drug/placebo administration on days 30, 60, 90, and 120. At the end of the study 5 animals from each group were sacrificed and their cochleae were harvested for histological investigation. Results No significant change in threshold (dB) was seen between the 4 groups. Histological studies of the cochleae revealed no hair cell damage in any of the groups. Conclusion Hydrocodone and acetaminophen/hydrocodone do not have an obvious deleterious effect on guinea pig cochlear function or structure. Significance This study may indicate that human hearing loss seen with abuse of acetaminophen/hydrocodone is multi-factorial and not just related to the drug abuse alone.

Production of the Soluble Form of KIT, s-KIT, Abolishes Stem Cell Factor-Induced Melanogenesis in Human Melanocytes

The signaling of stem cell factor (SCF) and its receptor KIT (membrane-bound KIT; m-KIT) plays an important role in melanocyte development, survival, proliferation, and melanogenesis. It has been demonstrated in other systems that a soluble form of m-KIT released from the cell surface (s-KIT) regulates SCF signaling, although there have been no reports pertaining to the existence and the biological role of s-KIT in melanocytes. In this study, we therefore examined the involvement of s-KIT in melanogenesis. Western blotting analysis revealed that treatment with phorbol 12-myristate-13-acetate (PMA) or 4-aminophenylmercuric acetate (APMA) induced s-KIT production in cultured human melanocytes. Inhibitors of tumor necrosis factor-alpha-converting enzyme (TACE) and metalloproteinases (MMPs) muted this release of s-KIT into the media. Human recombinant s-KIT added to melanocytes inhibited SCF-induced phosphorylation of m-KIT, resulting in suppression of SCF-induced melanogenesis. Additionally, APMA-induced s-KIT production abolished SCF-induced melanogenesis as effectively as a KIT-neutralizing antibody. Concomitantly, APMA and TACE inhibitors significantly decreased and increased melanin synthesis, respectively, in an in vitro skin model. Taken together, these findings provided an insight into the elaborate mechanism of SCF/m-KIT signaling in human melanocytes and suggested that production of s-KIT contributes to the regulation of human skin pigmentation. Journal of Investigative Dermatology (2008) 128, 1763-1772; doi:10.1038/jid.2008.9; published online 31 January 2008.

Feasibility of 99mTc-TRODAT-1 Micro-SPECT imaging of dopamine transporter in animal retinas

In this paper, 99mTc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with form deprivation myopia. Pigmented guinea pigs aged 3 weeks were devided into form deprivation myopia (FDM) group ( n=6) and normal control group ( n=6). The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4 th week after injection of 99mTc-TRODAT-1. The retinas were clearly resolved in the images. The ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the control eye (15.20±1.98), and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04). The results showed that 99mTc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina, and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes. Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.

Auditory Cortex Phase Locking to Amplitude-Modulated Cochlear Implant Pulse Trains

Cochlear implant speech processors transmit temporal features of sound as amplitude modulation of constant-rate electrical pulse trains. This study evaluated the central representation of amplitude modulation in the form of phase-locked firing of neurons in the auditory cortex. Anesthetized pigmented guinea pigs were implanted with cochlear electrode arrays. Stimuli were 254 pulse/s (pps) trains of biphasic electrical pulses, sinusoidally modulated with frequencies of 10-64 Hz and modulation depths of -40 to -5 dB re 100% (i.e., 1-56.2% modulation). Single- and multiunit activity was recorded from multi-site silicon-substrate probes. The maximum frequency for significant phase locking (limiting modulation frequency) was >or=60 Hz for 42% of recording sites, whereas phase locking to pulses of unmodulated pulse trains rarely exceeded 30 pps. The strength of phase locking to frequencies >or=40 Hz often varied nonmonotonically with modulation depth, commonly peaking at modulation depths around -15 to -10 dB. Cortical phase locking coded modulation frequency reliably, whereas a putative rate code for frequency was confounded by rate changes with modulation depth. Group delay computed from the slope of mean phase versus modulation frequency tended to increase with decreasing limiting modulation frequency. Neurons in cortical extragranular layers had lower limiting modulation frequencies than did neurons in thalamic afferent layers. Those observations suggest that the low-pass characteristic of cortical phase locking results from intracortical filtering mechanisms. The results show that cortical neurons can phase lock to modulated electrical pulse trains across the range of modulation frequencies and depths presented by cochlear implant speech processors.

Drinking water supplementation with ascorbate is not protective against UVR‐B‐induced cataract in the guinea pig

To study if ascorbate supplementation decreases ultraviolet radiation (UVR)-induced cataract development in the guinea pig. Sixty 6-9-week-old pigmented guinea pigs received drinking water supplemented with or without 5.5 mm l-ascorbate for 4 weeks. After supplementation, 40 animals were exposed unilaterally in vivo under anaesthesia to 80 kJ/m(2) UVR-B. One day later, the animals were killed and lenses were extracted. Degree of cataract was quantified by measurement of intensity of forward lens light scattering. Lens ascorbate concentration was determined with high-performance liquid chromatography (HPLC) with UVR detection at 254 nm. Twenty animals were used as non-exposed control. Supplementation increased lens ascorbate concentration significantly. In UVR-exposed animals, mean 95% confidence intervals (CIs) for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.54 +/- 0.07 (no ascorbate) and 0.83 +/- 0.05 (5.5 mm ascorbate). In non-exposed control animals, mean 95% CIs for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.72 +/- 0.12 (0 mm ascorbate) and 0.90 +/- 0.15 (5.5 mm ascorbate). All non-exposed lenses were devoid of cataract. Superficial anterior cataract developed in all UVR-exposed lenses. The lens light scattering was 39.2 +/- 14.1 milli transformed equivalent diazepam concentration (m(tEDC)) without and 35.9 +/- 14.0 m(tEDC) with ascorbate supplementation. Superficial anterior cataract develops in lenses exposed to UVR-B. Ascorbate supplementation is non-toxic to both UVR-B-exposed lenses and non-exposed control lenses. Ascorbate supplementation does not reduce in vivo lens forward light scattering secondary to UVR-B exposure in the guinea pig.

Estimation of a safety limit for ultraviolet radiation‐B (UVR‐B)‐induced cataract in an in vivo pigmented guinea pig model

Abstract Purpose: To establish a threshold measure, maximum tolerable dose (MTD), for avoidance of UVR‐B‐induced cataract in the pigmented guinea pig. Methods: Thirty female guinea pigs, five to nine weeks of age, were divided into 5 groups of 6 guinea pigs each. Pupils were dilated bilaterally before exposures. The guinea pigs were unilaterally exposed to UVR‐B under anesthesia in vivo, receiving between 0 and‐84.9 kJ/m2 over a duration of 60 minutes. Each guinea pig was sacrificed 24 hours after exposure. Lenses were extracted and photographed in vitro. Intensity of forward light scattering was measured for each lens. The data were analyzed with regression using a second order polynomial model, considering the first order term to be 0. The applied MTD concept is based on the UVR‐B dose response curve obtained for the pigmented guinea pig. Results: All of the guinea pigs exposed to UVR‐B developed cataracts in the anterior subcapsular region. MTD for avoidance of UVR‐B‐induced cataract was estimated to be 69.0 kJ/m2 in the pigmented guinea pig. Conclusions: The MTD for avoidance of UVR‐B‐induced cataract in the pigmented guinea pig is significantly higher than the threshold obtained by Pitts et al. in the pigmented rabbit. MTD is an appropriate method for estimation of toxicity for UVR‐B‐induced cataract in the guinea pig. The pigmented guinea pig is less sensitive to UVR‐B exposure than the pigmented rabbit, pigmented rat, and pigmented mouse.

Experimental estrogen-induced hyperprolactinemia results in bone-related hearing loss in the guinea pig

Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135-138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, in that study, it was not possible to determine whether hyperprolactinemia was a cause or an effect of the symptoms. To investigate the effect of hyperprolactinemia on inner ear function, we first developed a model of hyperprolactinemia in estrogen-primed Fischer 344 rats and then performed functional studies on pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, a hearing loss of approximately 30-40 dB across all frequencies, as indicated by the compound action potential audiogram. During the 3rd mo, the hearing loss continued to deteriorate. The threshold shifts were more substantial in males than in females. Observations under a dissection microscope revealed bone dysmorphology of the bulla and the cochlea. Light microscopy observations of cryostat sections confirmed bone-related pathology of the bony cochlear bulla and the cochlear wall and revealed morphopathology of the stria vascularis and spiral ligament. Scanning electron microscopy revealed loss of hair cells and stereocilia damage, in particular in the upper three cochlear turns and the two outermost hair cell rows. The data provide the first evidence of otic capsule and hair cell pathology associated with estrogen-induced prolonged hyperprolactinemia and suggest that conditions such as pregnancy, anti-psychotic drug treatment, aging, and/or stress might lead to similar ear dysfunctions.

Emmetropization and schematic eye models in developing pigmented guinea pigs

A model of the axial change in ocular parameters of the guinea pig eye from 2 to 825 days of age was developed and a corresponding paraxial schematic eye model applicable from 2 to 100 days of age was constructed. Axial distances increased logarithmically over time except for the lens in which growth was more complex. Over the first 30 days, ocular elongation was approximately linear: ocular length increased by 37 μm/day, the majority due lens expansion. The choroid and sclera thickened with age, while the retina thinned in proportion to the increased ocular size, and the model suggests that there is no small eye artefact for white light retinoscopy. Refractive error just after birth was +4.8 D but halved within the first week. Emmetropization occurred within the first month of life similar to that in other species when aligned at the point of sexual maturity and scaled by the time taken to reach adulthood. The power of the eye was 227 D at 2 days of age and reduced by 19.7 D by 100 days due to a 22% decrease in the power of the cornea. The posterior nodal distance (PND) was 4.7 mm at 30 days of age, with a maximum rate of change of 13 μm/day during the first week. The ratio of PND to axial length declined until at least 100 days of age, well after emmetropia was reached. This suggests that the maintenance of emmetropia is not sustained through proportional axial growth, but involves some active mechanism beyond simple scaling. The model predicts that 1 D of myopia requires an elongation of between 23 and 32 μm, depending upon age, suggesting that a resolution of at least 50 μm is required in methods used to determine the significance of ocular length changes in guinea pig models of refractive development. Retinal magnification averaged 80 μm/degree, and the maximum potential brightness of the retinal image was high, which together with a ratio of lens power to corneal power of 1.7–2.0 suggests that the guinea pig eye is adapted for noctural conditions.

Effects of a Single High Dose of Cisplatin on the Melanocytes of the Stria Vascularis in the Guinea Pig

The antineoplastic drug cisplatin is known to cause a reduction in endocochlear potential. The hypothesis to be tested was whether a single high dose of cisplatin affects the melanocytes by altering the expression of melanin. Pigmented guinea pigs received a bolus injection of cisplatin (8 mg/kg as a 15-second intravenous infusion). Auditory brainstem response (ABR) thresholds and morphological analysis of the hair cells and the stria vascularis were made 96 h after injection. ABR thresholds were elevated (15–40 dB) at 12–30 kHz and a significant loss of outer hair cells in the more basal regions was found. Cisplatin caused a significantly lower density of melanin in the intermediate cells in the basal region without any signs of apoptosis. Changes in melanin content were not noted in the middle or apical cochlear regions. Significant correlations were found between melanin density, ABR threshold shifts and outer hair cell loss in the region corresponding to 30 kHz. The findings reported here further support the multiple cytotoxic effect of cisplatin on the inner ear.

Crosslinked hydrogels for tympanic membrane repair

To provide a less expensive and more convenient protocol for the treatment of tympanic membrane perforations (TMPs). Several materials were prepared and compared for TMP repair including Carbylan-SX, Gelatin-DTPH-PEGDA (GX), Carbylan-S/Gelatin-DTPH (Carbylan-GSX) (injectable and sponge), Gelfoam, Epifilm, and crosslinked thiolated chondroitin sulfate (CS-DTPH-PEGDA [CS-SX]). Hartley pigmented guinea pigs (Elm Hill) underwent bilateral myringotomy with 1 ear left as a control and the other treated with one of the previously mentioned materials. Carbylan-GSX (injectable and sponge), Gelfoam with saline, and CS-SX had the shortest time for TMP closure. Epifilm, Carbylan, and gelatin preparations resulted in closure rates similar to controls. CS-SX showed a marked inflammatory reaction compared with controls and other materials based on neutrophil, lymphocyte, epitheloid counts, and degree of fibrosis. This study shows the validity of Carbylan-GSX compared with Gelfoam as a material to promote TMP closure in an acute TMP guinea pig model.

Streptomycin action to the mammalian inner ear vestibular organs: Comparison between pigmented guinea pigs and rats

Streptomycin is the antibiotic of choice to treat tuberculosis and other infectious diseases but it causes vestibular malfunction and hipoacusia. Rodents are usually employed as models of drug action to the inner ear and results are extrapolated to what happens in humans. In rats, streptomycin destroys macular sensory cells and does not affect cochlear ones, whereas in guinea pigs the contrary is true. Action on the vestibular cristae cells involved in vestibulo-ocular reflex integrity is less clear. Thus, we compared this response in both pigmented guinea pigs (Cavia cobaya) and rats (Rattus norvegicus) after parallel streptomycin chronic treatment. In guinea pigs, the reflex was obliterated along treatment time; in rats this behavior was not observed, suggesting that the end organ target was diverse. In recent studies, streptidine, a streptomycin derivative found in the blood of humans and rats treated with streptomycin, was the actual ototoxic agent. The putative streptomycin vestibular organ target observed in humans corresponds with the guinea pig observations. Results observed in rats are controversial: streptidine did not cause any damage either to vestibular cristae nor auditory cells. We hypothesize differential drug metabolism and distribution and conclude that results in laboratory animals may not always be applicable in the human situation.

Detection of UV-Induced Pigmentary and Epidermal Changes Over Time Using In Vivo Reflectance Confocal Microscopy

In vivo reflectance confocal microscopy (RCM) provides high-resolution optical sections of the skin in its native state, without needing to fix or section the tissue. Melanin provides an excellent contrast for RCM, giving a bright signal in the confocal images. The pigmented guinea-pig is a common animal model to study human pigment induction and modulation, as its tanning response is comparable to human tanning after exposure to ultraviolet radiation (UVR). We investigated the applicability of RCM to detecting UVR-induced pigmentary changes in this model. Animals were exposed to solar simulator radiation for 7 days. RCM was performed during the irradiation and follow-up period. Compared to non-irradiated skin, an increase in melanocyte size, dendricity, and number, as well as increased pigment in keratinocytes, was seen in the irradiated epidermis. Interestingly, these changes could be detected even before a tanning response was clinically visible. UVR-induced epidermal hyperplasia could also be detected and quantified. In conclusion, in vivo RCM is a sensitive non-invasive imaging technique that can repeatedly measure epidermal pigmentation and thickness, as demonstrated in the guinea-pig model. This technique should greatly enhance our appreciation of dynamic pigmentary changes in human or animal skin over time and in response to specific stimuli.

Preventive effects of vitamin E on short-term noise-induced hearing loss in guinea pigs

To study the preventive effects of vitamin E on short-term noise-induced hearing loss (NIHL). Forty-eight male pigmented guinea pigs were randomly divided into 6 groups, 8 animals in each group. The animals of group 1, 2, 3, 4 were exposed to the noise (4 kHz octave band noise, 100 dB SPL), 8 hours per day for 3 days consecutively and received normal saline, corn oil, 10 mg/kg vitamin E, 50 mg/kg vitamin E respectively daily by intraperitoneal injection from 3 days before the noise exposure, through the 3 noise exposure days to 3 days after the noise exposure. The animals of group 5 and group 6 days were not exposed to the noise but received normal saline and 50 mg/kg vitamin E injection respectively at the same time as that of group 1, 2, 3, 4. The preventive effects of vitamin E on NIHL were determined by comparing the threshold shifts of auditory brainstem responses (ABR) immediately, on the second day and on the 8th day after the exposure. The ABR threshold shifts immediately, on the second day and on the 8th day after the exposure for group 3 at 2, 4 and 8 kHz were (15.9 +/- 6.8), (39.4 +/- 4.8), (42.5 +/- 6.3), (0.3 +/- 2.5), (19.1 +/- 7.9), (21.9 +/- 6.4), (0.3 +/- 1.6), (10.9 +/- 8.6), (12.2 +/- 8.1) dB, respectively, which were significantly lower than those for group 1 [(30.9 +/- 11.3), (47.8 +/- 8.8), (49.7 +/- 6.9), (10.0 +/- 3.5), (29.1 +/- 6.5), (29.1 +/- 7.6), (4.7 +/- 3.6), (20.3 +/- 6.5), (17.5 +/- 9.0) dB, respectively] (P < 0.05). The ABR threshold shifts immediately, on the second day and on the 8th day after the exposure for group 4 at 2, 4 and 8 kHz were respectively (14.4 +/- 5.3), (36.6 +/- 4.4), (43.1 +/- 2.9), (0.3 +/- 2.5), (16.9 +/- 4.6), (19.4 +/- 3.2), (0.0 +/- 3.7), (7.5 +/- 4.2), (9.1 +/- 4.2) dB, which were significantly lower than those for group 1 (P < 0.05). Vitamin E has some preventive effects on the NIHL.

DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency

Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.

Preoperative antibiotic and steroid therapy and hearing loss caused by semicircular canal transection in pseudomonas otitis media

The purpose of this experiment was to determine whether preoperative administration of antibiotics and corticosteroids can attenuate the severity of hearing loss (HL) with semicircular canal (SC) transection in a guinea pig model of Pseudomonas aeruginosa (PA) otitis media (OM). Study design and setting Prospective and controlled. OM was induced in 64 pigmented guinea pigs by bilateral, transtympanic injection of PA. Two to 4 days later, 1 horizontal SC was randomly transected. In the 1st series, antibiotic therapy was initiated either immediately before or after surgery. In the 2nd series, all animals received preoperative antibiotics, and half received dexamethasone before surgery. Hearing was tested before and after surgery. PA was recovered in all ears. SC transection was associated with significant HL. HL was better in animals given antibiotics preoperatively (clicks, 16 versus 32 dB, P = 0.0220). Addition of preoperative steroids did not significantly further reduce HL (7 versus 14 dB for clicks, P = 0.6919). HL caused by SC transection in PA OM may be attenuated with preoperative antibiotic therapy in the guinea pig.

Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model

Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. B-2.

Hearing loss with semicircular canal transection and Pseudomonas aeruginosa otitis media

Objective To determine if Pseudomonas aeruginosa (PA) otitis media (OM) increases the risk of sensorineural hearing loss (SNHL) with semicircular canal transection in the guinea pig model. Methods PA was injected transtympanically into both middle ears of pigmented guinea pigs. Saline-injected animals served as controls. Two to 4 days after injection, one horizontal semicircular canal was transected and sealed. Hearing was tested using electrocochleography before and after transection. Results PA-OM was induced in all PA-injected ears. Five days after semicircular canal transection, click-evoked thresholds were significantly elevated in ears with PA-OM ( P = 0.00009) but not in saline-injected ears ( P = 0.398). Conclusion Violation of the inner ear in the presence of PA-OM is associated with increased risk of SNHL in the guinea pig. Significance Factors unique to PA infection may be responsible for SNHL with labyrinthine injury in humans with chronic otitis media.

Hearing loss and extent of labyrinthine injury in pseudomonas otitis media

Problem: Semicircular canal transection (SCT), in the presence of chronic suppurative otitis media (OM), usually leads to permanent, profound sensorineural hearing loss (SNHL). Models have suggested that pseudomonas or its toxins may be responsible, but SCT, in the presence of pseudomonas OM in the guinea pig, usually does not result in profound SNHL. The purpose of this study was to determine if the severity of SNHL, due to SCT in OM, is a function of the extent of the labyrinthine injury. Methods: Pseudomonas OM was induced bilaterally in pigmented guinea pigs. Two to four days later, SCT was performed in one ear on the horizontal canal, the superior canal, or both the horizontal and the superior canals. Auditory-evoked brainstem responses were measured both before and after SCT. Results: Pseudomonas OM was induced bilaterally in all animals. Elevation of click thresholds was found in almost all SCT ears of all 3 groups; however, there were no significant differences between groups. When comparing the SCT ear to the contralateral, internal control ear, average hearing losses in the horizontal, superior, and horizontal and superior labyrinthine ablation groups were 23, 27, and 24 dB (± 4.1, 4.0, and 4.2 dB), respectively. Conclusion: SCT in the presence of pseudomonas OM causes significant hearing loss in a guinea pig model. Significance: Sensorineural hearing loss secondary to semicircular canal transection may not correlate directly with the extent of vestibular labyrinthine injury. Support: None reported.

Optimum primary tone level setting for measuring high amplitude DPOAEs in guinea pigs

A special stimulus paradigm needs to be applied when distortion product otoacoustic emission (DPOAE) input/output functions are used to investigate the loss of sensitivity and loss of compression of outer hair cell cochlear amplifiers during noise exposure, drug treatment, etc. This stimulus paradigm should be able to reflect cochlear non-linear compressive sound processing known from direct basilar membrane measurements. Such a paradigm has already been established for humans that accounts for the different compression of the primary tones at the DPOAE generation site at f 2 with L 1=0.4 L 2+39 dB SPL (‘scissor paradigm’). The purpose of the present study was to develop an equivalent parameter setting for guinea pigs. Ninety-six different L 1– L 2 combinations were presented to 24 ears in 18 pigmented guinea pigs at seven f 2 frequencies between 2 and 16 kHz. L 2 ranged from 20 to 60 dB SPL, L 1 from 20 to 65 dB SPL. An extreme value analysis was performed to achieve the maximum DPOAE level for L 1 in relation to L 2. Linear regression analysis yielded a scissor paradigm specific to guinea pigs ( L 1=0.46 L 2+41 dB SPL) which is similar to that of humans.