A Randomised,Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery

Background

Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies.

Methods

We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo.

Findings

One year after surgery, high-frequency hearing had improved 2.7 ± 3.8 dB in the placebo group (67 patients analysed) and 2.4 ± 3.7 dB in the treated group (72 patients; means ± 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting.

Conclusions

N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.

Trial Registration

ClinicalTrials.gov NCT00525551     

Ship noise‐induced temporary hearing threshold shift in the Chinese sucker Myxocyprinus asiaticus (Bleeker, 1864)

The study objective was to explore the effects of noise generated by a 2000 hp containership on the reaction of Chinese sucker Myxocyprinus asiaticus. The noise was played back for various durations (1, 2, 4, 8, 24 h) at 142.8 dB re 1 μPa. Immediately after the noise exposure, hearing abilities of the fish were tested using the auditory evoked potential (AEP) protocol and compared with the response to a control group with no noise exposure. After 1 h noise exposure no significant differences were found compared to control fish; however, significant auditory threshold shifts began to occur at 800 Hz after 2 h of noise exposure. After 24 h of noise exposure, significant auditory threshold shifts were found at all tested frequencies (100–3000 Hz) when compared to control fish. Recoveries were also measured until the auditory thresholds returned to the hearing levels of the control fish. Auditory thresholds of all Chinese suckers fully returned to control levels within 96 h of recovery time. The results indicate that ship noise exposure can lead to threshold shifts in Chinese sucker and that these threshold shifts are temporary, referred to as temporary threshold shift (TTS).     

Optimal Dosage of Methylprednisolone for the Treatment of Sudden Hearing Loss in Geriatric Patients: A Propensity Score-Matched Analysis

We aimed to compare the treatment outcomes and the occurrence rates of adverse events associated with different steroid regimens in geriatric patients (aged 65 years or older) with unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). After thorough medical chart reviews of 109 patients with ISSNHL between May 2006 and December 2013, we performed a propensity score-matched analysis using previously known prognostic factors, steroid regimens, and other cointerventions. Patients were divided based on their steroid regimens into group I (which initially received 48 mg of methylprednisolone daily with a subsequently tapered dose) and group II (which initially received 24 mg of methylprednisolone daily with a subsequently tapered dose). We compared final hearing and the occurrence of adverse events between the two groups. As a result, 20 pairs of propensity score-matched patients (n = 40) were enrolled. Group I patients showed better final hearing levels compared with group II patients (42.00±22.35 dB and 57.38±26.40 dB, respectively), although this difference was marginally significant (p = 0.058). Based on the comparative analysis of each of the frequencies in the final audiograms, lower hearing thresholds at 2 KHz were observed in group I (p = 0.049). There was no significant difference in the occurrence of adverse effects between the two groups (p>0.05). In conclusion, conventional steroid regimens produced adverse event occurrence rates that were similar to those of low-dose treatment but may also have produced superior hearing recovery. The use of steroid dose reduction in geriatric patients with ISSNHL is not preferable to conventional steroid regimens.     

The Association between Metabolic Syndrome or Chronic Kidney Disease and Hearing Thresholds in Koreans: The Korean National Health and Nutrition Examination Survey 2009-2012

Background

The aim of this study was to determine whether metabolic syndrome (MetS) or chronic kidney disease (CKD) is associated with hearing thresholds in the general Korean population.

Patients and Methods

A total of 16,554 participants were included in this study. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III guidelines, and CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m² or a dipstick proteinuria result of ≥1+. The hearing thresholds were measured at 0.5, 1, 2, 3, 4, and 6 kHz. Low-frequency (Freq) was defined as pure-tone averages at 0.5 and 1 kHz, while Mid-Freq and High-Freq were defined as the average thresholds at mid-frequency (2 and 3 kHz) and high frequency (4 and 6 kHz), respectively.

Results

In men, the hearing thresholds were 15.1 ± 14.5 dB, 22.2 ± 21.3 dB, and 37.3 ± 26.5 dB for Low-, Mid-, and High-Freq, respectively. In women, the hearing thresholds were 14.9 ± 15.3 dB, 16.6 ± 18.0 dB, and 26.1 ± 21.5 dB for Low-, Mid-, and High-Freq, respectively. The hearing thresholds for men were significantly higher than the hearing thresholds for women in all 3 threshold categories. Male and female subjects with MetS or CKD had higher hearing thresholds than the subjects that did not have these disorders. In the multivariate analysis, MetS was associated with increased hearing thresholds in women, and CKD was associated with increased hearing thresholds in men and women.

Conclusion

MetS is associated with hearing thresholds in women, and CKD is associated with hearing thresholds in men and women. Therefore, patients with MetS or CKD should be closely monitored for hearing impairment.     

Coding of acoustic particle motion by utricular fibers in the sleeper goby, <Emphasis Type="Italic">Dormitator latifrons</Emphasis>

It is unknown whether the fish utricle contributes to directional hearing. Here, we report response properties of single utricular fibers in a teleost fish (Dormitator latifrons) to linear accelerations at various stimulus frequencies and axes. Characteristic frequencies ranged from 50–400 Hz (median=80 Hz), and best frequencies shifted from 50 to 250 Hz with stimulus level. Best sensitivity of utricular fibers was distributed from –70 to –40 dB re: 1 g (mean=–52 dB), which is about 30 dB less sensitive than saccular fibers. Q_50% fell between 0.16 and 11.50 (mean=2.04) at 15 dB above threshold. We observed temporal response patterns of entrained phase-locking, double phase-locking, phase-locked bursting, and non-phase-locked bursting. Most utricular fibers were directionally selective with various directional response profiles, and directional selectivity was stimulus-level dependent. Horizontal best-response axes were distributed in a 152° range while mid-sagittal best-response axes were clustered around the fish longitudinal axis, which is consistent with the horizontal orientation of the utricle and morphological polarizations of utricular hair cells. Therefore, results of this study indicate that the utricle in this vertebrate plays an auditory role in azimuth and that utricular fibers extend the response dynamic range of this species in directional hearing.     

Behavioral detection of acoustic particle motion by a teleost fish (Astronotus ocellatus): sensitivity and directionality

The physiology and morphology of auditory interneurons of a fly, the parasitoid Therobia leonidei, are described for the first time. 1. The hearing threshold has been determined with summed recordings of the neck connective. Females are most sensitive in a frequency range from 16 to 40 kHz (thresholds: around 45 dB SPL). This broad hearing range matches with the peak frequencies of the song spectra of host bushcricket species. Male flies are 10–20 dB less sensitive than females. 2. The sensory cells of the prosternal tympanal organ of T. leonidei project into the thoracico-abdominal ganglion complex with arborizations in all three thoracic neuromeres. 3. Three types of ascending auditory interneurons were identified by their morphology and response properties. These have arborizations in all three thoracic neuromeres and terminate soma-contralaterally in the brain. At least three other neuron types were also identified according to response properties alone. The neurons show similar spectral tuning but different sensitivities.     

Hearing in blind subterranean Zambian mole-rats (Cryptomys sp.): collective behavioural audiogram in a highly social rodent

Thresholds for pure tone detection were examined in the common mole-rat, Cryptomys sp. (Bathyergidae, Rodentia) using a positive reinforcement procedure. To bypass the problems connected with testing isolated individuals of this extremely social species, a collective behavioural audiogram was determined for a family group of seven mole-rats. Within the tested frequency range of 225 to 18 kHz, the lowest thresholds (as low as 7.5 dB SPL, on average 24 dB SPL) were found at 800 Hz, the upper limit of hearing (at the level of 60 dB SPL) was at 18 kHz. The behavioural audiogram combines the results of previous studies on hearing in this species. It resembles the distortion threshold curve but differs from neurophysiological data as far as the high frequency cutoff is concerned. On the other hand, the region of the best hearing sensitivity is narrow in behavioural audiogram and neurophysiological curves but rather broad in the distortion threshold curve. In general, the behavioural audiogram of Cryptomys is in many aspects comparable with the available audiograms of other subterranean rodents. Accepted: 18 February 1997     

Potential effects of underwater noise from wind turbines on the marbled rockfish (Sebasticus marmoratus)

Environmental assessments of underwater noise on marine species must be based on species-specific hearing abilities. This study was to assess the potential impact of underwater noise from the East China Sea Bridge wind farm on the acoustic communication of the marbled rockfish. Here, the 1/3 octave frequency band of underwater noise was 125 Hz with the level range of 78–96 dB re 1 μPa, recorded at distances between 15-20m from the foundation at wind speed of 3–5 m/s. Auditory evoked potential (AEP) and passive acoustic techniques were used to determine the hearing abilities and sound production of the fish. The resultes showed the lowest auditory threshold of Sebastiscus marmoratus was 70 dB at 150 Hz matching the disturbance sound ranging 140–180 Hz, which indicating the acoustic communication used in this species. However, the frequency and level of turbine underwater noise overlapped the auditory sensitivity and vocalization of Sebastiscus marmoratus. The wind turbine noise could be detected by fish and may have a masking effect on their acoustic communication. This result can be applied for further to the assessent of fish species released into offshore wind farm marine ranch.     

Correlations between hearing and sound production in piranhas

Summary In order to determine whether correlations exist between hearing and the known soundproduction abilities in piranhas (Serrasalmus nattereri), behavioral auditory thresholds were obtained with continuous tones and tone pulses. A new avoidance conditioning method was developed, where fin movements of caged animals were taken as response to a tone. The mean values of the far-field audiogram ranged from –26 dB re. 0.1 Pa at 80 Hz to a low point of about –43 dB between 220–350 Hz and rose to –14 dB at 1500 Hz. The frequency spectrum of typical drumming sounds (barks) covers the range of best hearing (100–600 Hz).Piranhas are able to integrate temporally acoustic signals: in threshold investigations with repeated tone pulses, the thresholds rose approximately exponentially with decreasing pulse duration and repetition rate; thresholds of single pulses were higher with shorter pulses. The temporal patterning of the calls and the temporal integration ability are well correlated in piranhas, optimizing intraspecific detectability and total length of sound production with respect to the fatigue characteristics of drumming muscles and habituation of the neural pacemaker.The lagenae of the piranhas were found to face laterofrontally; this is thought to be a morphological adaptation to sound production, saving the lagenae from excessive strain during activation of the drumming muscles.Abbreviations Cl acoustic condition 1, where a board with the air loudspeaker rested on the experimental tank upon a layer of felt - C2 acoustic condition 2, where the loudspeaker was freely mounted 20 cm above the water surface - d _p pulse duration - f _p pulse repetition rate - D duty cycle     

Antitumor Activity of a Combination of rAd2p53 Adenoviral Gene Therapy and Radiotherapy in Esophageal Carcinoma

The objective of this study was to determine if a combination of recombinant adenovirus 2 p53 (rAd2p53) gene therapy and radiotherapy would have significantly improved outcome from esophageal carcinoma when compared to radiotherapy (RT) alone. Forty-five patients diagnosed with esophageal carcinoma (confirmed squamous cell carcinoma) were randomly assigned to one of two study arms: treatment group: rAd2p53 gene therapy + RT (n = 22); and control group: radiotherapy (n = 23). For the treatment group, rAd2p53 was injected into multiple areas of the lesion once a week for 6 weeks avoiding deep ulcers points. RT was administered after 3 days of injection of rAd2p53. Patients in the control group only received radiotherapy. The overall response rate was significantly higher in the treatment group than in control group (P < 0.05). Furthermore, the complete response rate was 3 times higher in the treatment group than in the control group (P < 0.05). Transient fever and pain at injection site were the only side effects mentioned in the treatment group. In conclusion, this recombinant virus–RT combination is significantly more beneficial in palliation than RT alone, with minor side affects. However, its role as neoadjuvant therapy prior to surgical resection needs to be further investigated.     

Cigarette Smoking Causes Hearing Impairment among Bangladeshi Population

Lifestyle including smoking, noise exposure with MP3 player and drinking alcohol are considered as risk factors for affecting hearing synergistically. However, little is known about the association of cigarette smoking with hearing impairment among subjects who carry a lifestyle without using MP3 player and drinking alcohol. We showed here the influence of smoking on hearing among Bangladeshi subjects who maintain a lifestyle devoid of using MP3 player and drinking alcohol. A total of 184 subjects (smokers: 90; non-smokers: 94) were included considering their duration and frequency of smoking for conducting this study. The mean hearing thresholds of non-smoker subjects at 1, 4, 8 and 12 kHz frequencies were 5.63±2.10, 8.56±5.75, 21.06±11.06, 40.79±20.36 decibel (dB), respectively and that of the smokers were 7±3.8, 13.27±8.4, 30.66±12.50 and 56.88±21.58 dB, respectively. The hearing thresholds of the smokers at 4, 8 and 12 kHz frequencies were significantly (p<0.05) higher than those of the non-smokers, while no significant differences were observed at 1 kHz frequency. We also observed no significant difference in auditory thresholds among smoker subgroups based on smoking frequency. In contrast, subjects smoked for longer duration (>5 years) showed higher level of auditory threshold (62.16±19.87 dB) at 12 kHz frequency compared with that (41.52±19.21 dB) of the subjects smoked for 1-5 years and the difference in auditory thresholds was statistically significant (p<0.0002). In this study, the Brinkman Index (BI) of smokers was from 6 to 440 and the adjusted odds ratio showed a positive correlation between hearing loss and smoking when adjusted for age and body mass index (BMI). In addition, age, but not BMI, also played positive role on hearing impairment at all frequencies. Thus, these findings suggested that cigarette smoking affects hearing level at all the frequencies tested but most significantly at extra higher frequencies.     

Advanced Beamformers for Cochlear Implant Users: Acute Measurement of Speech Perception in Challenging Listening Conditions

Objective

To investigate the performance of monaural and binaural beamforming technology with an additional noise reduction algorithm, in cochlear implant recipients.

Method

This experimental study was conducted as a single subject repeated measures design within a large German cochlear implant centre. Twelve experienced users of an Advanced Bionics HiRes90K or CII implant with a Harmony speech processor were enrolled. The cochlear implant processor of each subject was connected to one of two bilaterally placed state-of-the-art hearing aids (Phonak Ambra) providing three alternative directional processing options: an omnidirectional setting, an adaptive monaural beamformer, and a binaural beamformer. A further noise reduction algorithm (ClearVoice) was applied to the signal on the cochlear implant processor itself. The speech signal was presented from 0° and speech shaped noise presented from loudspeakers placed at ±70°, ±135° and 180°. The Oldenburg sentence test was used to determine the signal-to-noise ratio at which subjects scored 50% correct.

Results

Both the adaptive and binaural beamformer were significantly better than the omnidirectional condition (5.3 dB±1.2 dB and 7.1 dB±1.6 dB (p<0.001) respectively). The best score was achieved with the binaural beamformer in combination with the ClearVoice noise reduction algorithm, with a significant improvement in SRT of 7.9 dB±2.4 dB (p<0.001) over the omnidirectional alone condition.

Conclusions

The study showed that the binaural beamformer implemented in the Phonak Ambra hearing aid could be used in conjunction with a Harmony speech processor to produce substantial average improvements in SRT of 7.1 dB. The monaural, adaptive beamformer provided an averaged SRT improvement of 5.3 dB.     

Ten-year survival analysis for renal carcinoma patients treated with an autologous tumour lysate vaccine in an adjuvant setting

About 30% of renal cell carcinomas (RCC) will develop recurrence after surgery. Despite evidence for a significantly improved survival by autologous tumour cell vaccination therapy, the procedure has not become standard. Between August 1993 and December 1996, 1,267 RCC patients undergoing radical nephrectomy in 84 German hospitals were subsequently treated by autologous tumour cell vaccination therapy. The study group comprised 692 patients with complete follow-up (stages pT2-3, pNx-2, M0 based on the TNM classification, 4th edition). Subsequent propensity-score matching according to 7 defined criteria with 861 control patients undergoing nephrectomy alone without adjuvant treatment at the Carl-Thiem-Hospital Cottbus, resulted in 495 matched pairs. Overall and stage-specific survival rates were analysed after a median follow-up of 131 months. The 5- and 10-year overall survival (OS) rates were 80.6 and 68.9% in the vaccine group and 79.2 and 62.1% in the control group (p = 0.066). Patients with pT3 stage RCC revealed 5- and 10-year OS rates of 71.3 and 53.6% in the study group and 65.4 and 36.2% in the control group (p = 0.022). In multivariable analysis, patients in the vaccine group showed a significantly improved survival both in the whole study group (HR = 1.28, p = 0.030) and in the subgroup presenting with pT3 stage tumours (HR = 1.67, p = 0.011). Adjuvant treatment with autologous vaccination therapy resulted in a significantly improved overall survival in pT3 stage RCC patients, suggesting benefit especially in this subgroup. However, controlled clinical trials integrating the recent TNM classification and further risk constellations are required to define additional patient groups that may derive benefit from this treatment.     

Treatment with Huperzine A Improves Cognition in Vascular Dementia Patients

In the present study, we tested the efficacy and safety of Huperzine A in treatment of mild to moderate vascular dementia (VaD). This was a randomized, double-blinded, placebo-controlled study with 78 patients with mild to moderate VaD. The participants were randomized to receive either vitamin C (100-mg bid) as placebo (n = 39) or Huperzine A (0.1-mg bid) (n = 39) for 12 consecutive weeks. The mini-mental state examination (MMSE), clinical dementia rating (CDR), and activities of daily living (ADL) scores were used for the assessment of cognition. The assessments were made prior to treatment, and 4, 8, and 12 weeks of the treatment. The adverse effects of the treatment were also recorded. After 12 weeks of treatment, the MMSE, CDR, and ADL scores significantly improved in the Huperzine A group (P < 0.01 for all comparisons), whereas the placebo group did not show any such improvement (P > 0.05 for all comparisons). No serious adverse events were recorded during the treatment. Conclusion: Huperzine A can significantly improve the cognitive function in patients with mild to moderate vascular dementia. Further, the medicament is safe.     

Effect of chilling on porcine germinal vesicle stage oocytes at the subcellular level

The potential subcellular consequence of chilling on porcine germinal vesicle (GV) stage oocytes was examined. Prior to in vitro maturation (IVM), Cumulus-oocyte complexes (COCs) freshly collected from antral follicles (3–6 mm in diameter) were evenly divided into four groups and immediately incubated in PVA-TL-HEPES medium at the temperature of 39 °C (control group), 23 °C (room temperature), 15 °C and 10 °C for 10 min, respectively. Following 42 h of IVM at 39 °C, the survival rates were examined. There was no significant difference between the survival rate of 23 °C chilled group and control group (77.92 and 91.89%), but the survival rate of 15 and 10 °C chilled group were significantly decreased (46.34 and 4.81%, P < 0.01). A further experiment on15 °C group showed that most oocytes died from 2 to 4 h of IVM. In order to investigate the effects of chilling on oocytes at the subcellular level, the control and 15 °C chilled group COCs fixed at different time points of the IVM cultures (2, 2.5, 3, 3.5 and 4 h of IVM) were prepared for transmission electron microscope (TEM) observation. As the result, compared with the control group, there were two significant changes in the ultrastructural morphology of 15 °C treatment group: (1) dramatic reduction of heterogeneous lipid, (2) disorganized mitochondria–endoplasmic reticulum–lipid vesicles (M–E–L) combination. These results indicate that 15 °C is a critical chilling temperature for porcine GV stage oocyte and the alteration of cellular chemical composition and the destruction of M–E–L combination maybe responsible for chilling injury of porcine oocyte at this stage.     

Auditory response characteristics of the piebald odorous frog and their implications

The piebald odorous frog (Odorrana schmackeri), the large odorous frog (Odorrana livida) and the concave-eared torrent frog (Amolops tormotus) are sympatric species living near the same torrent streams in the vicinity of Mt. Huangshan, China. A recent study demonstrated that A. tormotus can use sound signals involving ultrasonic components for communication in a noisy environment, and another sympatric species, O. livida, can also perceive ultrasonic sound. Here we report data on the hearing range of O. schmackeri by studying auditory evoked potentials and single-unit data from the torus semicircularis. This frog exhibits its two most sensitive peaks at 2 kHz and 3.5–4.0 kHz with thresholds <42 dB SPL, with an upper frequency limit of hearing at 8.5 kHz with threshold of 87 dB SPL. The upper limit is much lower than those of O. livida and A. tormotus, at 22 and 34 kHz, respectively. It suggests that sympatric species may respond differently to similar environmental selection pressures sculpting auditory communication systems.     

Psychophysical and neurophysiological hearing thresholds in the bat <Emphasis Type="Italic">Phyllostomus </Emphasis><Emphasis Type="Italic">discolor</Emphasis>

Absolute hearing thresholds in the spear-nosed bat Phyllostomus discolor have been determined both with psychophysical and neurophysiological methods. Neurophysiological data have been obtained from two different structures of the ascending auditory pathway, the inferior colliculus and the auditory cortex. Minimum auditory thresholds of neurons are very similar in both structures. Lowest absolute thresholds of 0 dB SPL are reached at frequencies from about 35 to 55 kHz in both cases. Overall behavioural sensitivity is roughly 20 dB better than neural sensitivity. The behavioural audiogram shows a first threshold dip around 23 kHz but threshold was lowest at 80 kHz (−10 dB SPL). This high sensitivity at 80 kHz is not reflected in the neural data. The data suggest that P. discolor has considerably better absolute auditory thresholds than estimated previously. The psychophysical and neurophysiological data are compared to other phyllostomid bats and differences are discussed. S. Hoffmann, L. Baier, F. Borina contributed equally to this work.     

Absolute hearing thresholds and critical masking ratios in the European barn owl: a comparison with other owls

Absolute thresholds and critical masking ratios were determined behaviorally for the European barn owl (Tyto alba guttata). It shows an excellent sensitivity throughout its hearing range with a minimum threshold of −14.2 dB sound pressure level at 6.3 kHz, which is similar to the sensitivity found in the American barn owl (Tyto alba pratincola) and some other owls. Both the European and the American barn owl have a high upper-frequency limit of hearing exceeding that in other bird species. Critical masking ratios, that can provide an estimate for the frequency selectivity in the barn owl's hearing system, were determined with a noise of about 0 dB spectrum level. They increased from 19.1 dB at 2 kHz to 29.2 dB at 8 kHz at a rate of 5.1 dB per octave. The corresponding critical ratio bandwidths were 81, 218, 562 and 831 Hz for test-tone frequencies of 2, 4, 6.3 and 8 kHz, respectively. These values indicate, contrary to expectations based on the spatial representation of frequencies on the basilar papilla, increasing bandwidths of auditory filters in the region of the barn owl's auditory fovea. This increase, however, correlates with the increase in the bandwidths of tuning curves in the barn owl's auditory fovea. Accepted: 27 November 1997     

Effect of Ganciclovir on murine cytomegalovirus-induced hearing loss in a mouse model

We evaluated the effect of Ganciclovir on murine cytomegalovirus (MCMV)-induced hearing impairment in a mouse model by studying modulations in auditory brainstem response (ABR) and pathological changes in the inner ear. MCMV infection was established via trans-brain. For this purpose, 24 BALB/c newborn mice were randomly and equally divided into control group (10 μl of sterile normal saline was injected); model group (10 μl of MCMV TCID50—10⁴ IU/0.1 ml was injected); and interfered group (Trans-brain MCMV; Ganciclovir at the rate of 60 mg/kg was intraperitoneally injected). ABR audiometry was performed after 14 days. Acoustic vesicles were obtained for MCMV-PCR analysis and histopathological examination. Comparing ABR in model group against controls, incubation period of wave was lengthened (F = 9.151, P = 0.011–0.05) and wave amplitude was cut down (F = 5.095, P = 0.043–0.05). Comparing ABR in model group against interfered group, incubation period and amplitude of wave were F = 13.797 (P = 0.003–0.05) and F = 14.587 (P = 0.002–0.05), respectively. Cochlear histopathological changes in model group included thickening of vestibular membrane, lymphocytic infiltration, and fibrous degeneration of cochlear duct. In Ganciclovir interfered group, however, these pathologic changes were less significant as compared with those of model group. We, therefore, conclude that Ganciclovir treatment at the early stage of MCMV-induced hearing impairment inhibits the disease progression in infected mice.     

Assessment of the genotoxicity of imidacloprid and metalaxyl in cultured human lymphocytes and rat bone-marrow

Imidacloprid and metalaxyl are two pesticides that are widely used in agriculture, either separately, or in combination. These agents were studied for their possible genotoxic effects with respect to the following cytogenetic end-points: (1) in vitro micronucleus (MN) formation and sister-chromatid exchange (SCE) induction in human lymphocytes and (2) in vivo micronucleus induction in polychromatic erythrocytes (PCEs) of the rat bone-marrow. The results of the MN analysis indicate that MN frequencies after treatment with both pesticides, separately or as a mixture, do not significantly differ from those in the controls except after treatment with metalaxyl alone at 50 μg/ml (p < 0.05). The results of the SCE analysis show that SCE frequencies after treatment with imidacloprid do not differ significantly from those in the controls. A statistically significant increase (p < 0.05) in SCE frequency resulted from treatments with metalaxyl at 5, 10 and 100 μg/ml and with the combination of imidacloprid and metalaxyl at 100 and 200 μg/ml. Finally, the in vivo micronucleus assay with rat bone-marrow polychromatic erythrocytes showed a statistically significant effect upon separate treatments with imidacloprid and metalaxyl at doses of 300 mg/kg body weight (b.w.) (p < 0.01) or upon combined treatment with 200 mg/Kg b.w. (p < 0.001) and 400 mg/kg b.w. (p < 0.05).