Measuring the middle-ear reflex: A quantitative method to assess effects of industrial solvents on central auditory pathways.

Volatile organic solvents are frequently present in industrial atmospheres. Their lipophilic properties mean they quickly reach the brain following inhalation. Acute exposure to some solvents perturbs the middle ear reflex, which could jeopardize cochlear protection against loud noises. As the physiological mechanisms involved in this protective reflex are highly complex, in vivo rodent models are required to allow rapid and reliable identification of any adverse effects of solvents on the middle ear reflex (MER). In this study, MER amplitude was measured in anesthetized Brown-Norway rats by monitoring the decrease in distortion product otoacoustic emissions (DPOAEs) caused by a contralateral stimulation. Our screening test consisted in measuring the impact of inhalation of solvent vapors at 3000 ppm for 15 min on the MER amplitude. We had previously studied a selection of aromatic solvents with this model; here, we extended the analysis to volatile compounds from other chemical families. The results obtained shed light on the mechanisms involved in the interactions between solvents and their neuronal targets. Thus, benzene and chlorobenzene had the greatest effect on MER (≥ + 1.8 dB), followed by a group composed of toluene, styrene, p-xylene, m-xylene, tetrachloroethylene and cyclohexane, which had a moderate effect on the MER (between + 0.3 and + 0.7 dB). Finally, trichloroethylene, n-hexane, methyl-ethyl-ketone, acetone, o-xylene, and ethylbenzene had no effect on the MER. Thus, the effect of solvents on the MER is not simply linked to their lipophilicity, rather it depends on specific interactions with neuronal targets. These interactions appear to be governed by the compound's chemical structure, e.g. the presence of an aromatic ring and its steric hindrance. In addition, perturbation of the MER by a solvent is independent of its toxic effects on cochlear cells. As the MER plays a protective role against exposure to high-intensity noises, these findings could have a significant impact in terms of prevention for subjects exposed to both noise and solvents.

[Diagnostics and Therapy of Idiopathic Sudden Sensorineural Hearing Loss]. / Diagnostik und Therapie des Hörsturzes.

This article reviews recent aspects of diagnostics, differential diagnostics and evidence in systemic and local therapy of idiopathic, sudden, sensorineural hearing loss (ISSHL). Since a number of disorders can be accompanied by sudden hearing loss a meaningful and targeted diagnostic strategy is of utmost importance. An important differential diagnosis of sudden hearing loss are intralabyrinthine schwannomas (ILS). The incidence of ILS is probably significantly underestimated. This may be due to the lack of awareness or lack of explicit search for an intralabyrinthine tumor on MRI or an inappropriate MRI technique ('head-MRI' instead of 'temporal bone-MRI' with too high slice thickness) for the evaluation of sudden hearing loss. Therefore, the request to the radiologist should specifically include the question for (or exclusion of) an ILS. With special MRI techniques, it is today possible to visualize an endolymphatic hydrops. The evidence in the therapy of ISSHL is - with respect to quality not quantity of studies - unsatisfying. The value of systemically (low dose) or intratympanically applied corticosteroids in the primary treatment of ISSHL is still unclear. In order to investigate the efficacy and safety of high dose corticosteroids in primary treatment for ISSHL a national, multicenter, three-armed, randomized, triple-blind controlled clinical trial is currently performed in Germany (http://hodokort-studie.hno.org/). After insufficient recovery of threshold with systemic therapy of ISSHL, intratympanic corticosteroid therapy appears to be associated with a significantly higher chance of improvement of hearing threshold than no therapy or placebo. Both, hearing gain and final hearing thresholds, however, appear to be independent of the start of secondary therapy. Based on the currently available data from clinical studies, no recommendation can be made with respect to type of corticosteroid and specifics of the intratympanic application protocol.

Membrane fluidity does not explain how solvents act on the middle-ear reflex.

Some volatile aromatic solvents have similar or opposite effects to anesthetics in the central nervous system. Like for anesthetics, the mechanisms of action involved are currently the subject of debate. This paper presents an in vivo study to determine whether direct binding or effects on membrane fluidity best explain how solvents counterbalance anesthesia's depression of the middle-ear reflex (MER). Rats were anesthetized with a mixture of ketamine and xylazine while also exposed to solvent vapors (toluene, ethylbenzene, or one of the three xylene isomers) and the amplitude of their MER was monitored. The depth of anesthesia was standardized based on the magnitude of the contraction of the muscles involved in the MER, determined by measuring cubic distortion product oto-acoustic emissions (DPOAEs) while triggering the bilateral reflex with contralateral acoustic stimulation. The effects of the aromatic solvents were quantified based on variations in the amplitude of the DPOAEs. The amplitude of the alteration to the MER measured in anesthetized rats did not correlate with solvent lipophilocity (as indicated by logKow values). Results obtained with the three xylene isomers indicated that the positions of two methyl groups around the benzene ring played a determinant role in solvent/neuronal cell interaction. Additionally, Solid-state Nuclear Magnetic Resonance (NMR) spectra for brain microsomes confirmed that brain lipid fluidity was unaffected by solvent exposure, even after three days (6h/day) at an extremely high concentration (3000ppm). Therefore, aromatic solvents appear to act directly on the neuroreceptors involved in the acoustic reflex circuit, rather than on membrane fluidity. The affinity of this interaction is determined by stereospecific parameters rather than lipophilocity.

Antifibrotic effect of dexamethasone/alginate-coated silicone sheet in the abraded middle ear mucosa.

Silicone sheet is a material which is commonly used in middle ear surgery to prevent the formation of adhesions between the tympanic membrane and the medial bony wall of the middle ear cavity. However, silicone sheet can induce a tight and hard fibrous capsule in the region of the stapes, and this is particularly common in cases of eustachian tube dysfunction. As a result of the fibrous encapsulation around the silicone sheet, postoperative aeration of the stapes can be interrupted causing poor hearing gain. In this study, we performed an in vitro and in vivo evaluation of the antifibrotic effects of a dexamethasone and alginate (Dx/alginate) coating on silicone sheet. The Dx/alginate-coated silicone sheets were fabricated using a plasma-treatment and coating method. The Dx/alginate-coated silicone sheets effectively limited in vitro fibroblast attachment and proliferation due to the controlled release of Dx, which can be modified by manipulation of the alginate coating. For the in-vivo evaluation, guinea pigs (albino, male, weighing 250g) were divided into two groups, with the control group (n=5) implanted with silicone sheet and the test group (n=5) receiving Dx/alginate-coated silicone sheet. Animals were sacrificed 3 weeks after implantation, and histological analysis was performed using hematoxylin and eosin (H&E) and immunohistochemical staining techniques. Dx/alginate-coated silicone sheets showed marked inhibition of fibrosis in both the in vitro and in vivo studies. Silicone sheet that incorporates a Dx/alginate coating can release Dx and inhibit fibrosis in the middle ear. This material could be utilized in middle ear surgery as a means of preserving proper aeration and hearing gain following ossiculoplasty.

In vitro Activity of Cefditoren against Middle Ear Fluid Isolates from Costa Rican Children with Otitis Media.

Otitis media (OM) is one of the most common infections in children, Streptococcus pneumoniae and nontypable Haemophilus influenzae being the two most common pathogens isolated in the middle ear fluid (MEF) of children with OM. Cefditoren is a third-generation cephalosporin with broad-spectrum antibacterial activity, including activity against those pathogens commonly causing OM, with enhanced stability against common ß-lactamases. The main objective of this study was to evaluate the in vitro activity of cefditoren against pathogens collected from the MEF of Costa Rican children with OM between 2006 and 2011. A total of 715 samples were analyzed. Among the 89 S. pneumoniae strains that were penicillin-nonsusceptible, only 7% were cefditoren-resistant according to Spanish Regulatory Agency criteria; among the H. influenza and M. catarrhalis isolates obtained, 100 and 90% of the isolates, respectively, were cefditoren-susceptible. MIC50/90 against the 207 PCV-13 S. pneumoniae serotyped strains and the 79 serotypes not covered by PCV-13 for cefditoren were 0.03/1 and 0.03/0.12 mg/l, respectively. For both amoxicillin-susceptible and resistant H. influenzae strains, the MIC range against cefditoren was from ≤0.015 to 0.06 mg/l as well. In conclusion, the confirmation of the wide spectrum of activity of cefditoren and its intrinsic strength against resistant strains allows us to suggest that cefditoren might be included as one of the best choices among antibiotics that are widely used in empiric therapy for OM in pediatric patients.

Electromyographic response of facial nerve stimulation under different levels of neuromuscular blockade during middle-ear surgery.

OBJECTIVE: To investigate facial nerve monitoring in patients receiving the partial nondepolarizing neuromuscular blocking agents (NMBAs), remifentanil and propofol. METHODS: Patients with normal facial function and advanced middle-ear disease were enrolled. For total intravenous anaesthesia (TIVA), propofol and remifentanil were infused as induction/maintenance anaesthesia. Stimulation thresholds and amplitudes were recorded at each train-of-four (TOF) nerve stimulation level. Time differences between start of TOF and electromyographic (EMG) amplitude decreases (Ti), and between complete recovery of TOF and EMG amplitudes (Tr), were calculated. RESULTS: Fifteen patients were enrolled. Mean ± SD Ti was 3.4 ± 1.28 min; Tr was 18.7 ± 4.41 min. Amplitude of stimulation was apparent mostly at TOF level 1. In most cases, no or a weak response (<100 µV) was observed at TOF 0. Mean ± SD threshold of electrical stimulation was 0.31 ± 0.10 mA at TOF 1. At TOF > 2, all cases showed EMG response on electrical stimulation. CONCLUSIONS: Induction of TIVA using propofol and remifentanil provided reliable conditions for delicate microsurgery. Minimal NMBA use, considered as producing TOF levels >1, was sufficient for facial nerve monitoring in neuro-otological surgery.

Inhaled toluene can modulate the effects of anesthetics on the middle-ear acoustic reflex.

Toluene (Tol) is an organic solvent widely used in the industry. It is also abused as an inhaled solvent, and can have deleterious effects on hearing. Recently, it was demonstrated that Tol has both anticholinergic and antiglutamatergic effects, and that it also inhibits voltage-dependent Ca(2+) channels. This paper describes a study of the effects of inhaled Tol on rats anesthetized with isoflurane, pentobarbital, or a mixture of ketamine/xylazine. Hearing was tested using distortion product oto-acoustic emissions (DPOAEs) associated with a contralateral noise to evaluate contraction of the middle-ear muscles. This allowed us to assess the interactions between the effects of Tol and anesthesia on the central nervous system (CNS). Although both anesthetics and Tol are known to inhibit the middle-ear acoustic reflex, our data indicated that inhaled Tol counterbalances the effects of anesthetic in a dose-dependent manner. In other terms, Tol can increase the amplitude of the middle-ear reflex in anesthetized rats, whatever the nature of the anesthetic used. This indicates that inhaling Tol (a Ca(2+)-channel-blocking drug) modifies the potency of anesthesia, and thereby the amplitude of the middle-ear reflex.

Intratympanic dexamethasone as initial therapy for idiopathic sudden sensorineural hearing loss: Clinical evaluation and laboratory investigation.

OBJECTIVE: To evaluate the effect of intratympanic dexamethasone (ITD) as initial therapy for idiopathic sudden sensorineural hearing loss (ISSHL) as well as to determine the concentration-dependent time course distribution of dexamethasone in the inner ear. METHODS: Sixty-six patients with profound ISSHL were included. Twenty-two were treated with ITD and the rest as control. Audiograms were performed before the treatment and one month afterwards. In the animal study, dexamethasone of different concentrations (5, 10 and 20mg/ml) was injected into the tympanums of three groups of SD rats (Groups A, B and C), their inner ears dissected free at various postinjection survival intervals. Immunofluorescence was applied to detect the locations of dexamethasone. RESULTS: The overall rate of good prognosis was 77.27% in ITD group, which was not significantly different from 81.82% in the control group. In the animal study, the higher local concentration and longer lasting period was found in Groups B and C. CONCLUSIONS: ITD at 5mg/ml did not add effect to systemic steroids in improving hearing outcomes in patients with ISSHL. An increase in dexamethasone concentration led to large variations in pharmacokinetics in animal study, showing potential value in optimizing the drug delivery protocols and improving the therapeutic results.

Neuronal circuits involved in the middle-ear acoustic reflex.

Human and animal studies have shown that certain aromatic solvents such as toluene can cause hearing loss and can exacerbate the effects of noise. The latter effects might be due to a modification of responses of motoneurons controlling the middle-ear acoustic reflex. In the present investigation, the audition of Long-Evans rats was evaluated by measuring cubic (2f1 - f2) distortion otoacoustic emissions (f1 = 8000 Hz; f2 = 9600 Hz; f1/f2 = 1.2) prior to, during, and after activation of the middle-ear acoustic reflex. A noise suppressor was used to modify the amplitude of the 2f1 - f2 distortion otoacoustic emissions. It was delivered either contralaterally (band noise centered at 4 kHz), or ipsilaterally (3.5 kHz sine wave) to test the role played by the central auditory nuclei. This audiometric approach was used to study the physiological efficiency of the middle-ear acoustic reflex during an injection of a bolus of Intralipid (as a vehicle) containing 58.4, 87.4, or 116.2mM toluene via the carotid artery. The results showed that toluene could either increase or decrease middle-ear acoustic reflex efficiency, depending on the toluene concentration and the ear receiving noise suppressor. A new neuronal circuit of the middle-ear acoustic reflex has been proposed to explain findings obtained in this investigation. Finally, the depressing action of toluene on the central auditory nuclei driving the middle-ear acoustic reflex might explain the synergistic effects of a co-exposure to noise and aromatic solvents.

Toluene can perturb the neuronal voltage-dependent Ca2+ channels involved in the middle-ear reflex.

Numerous laboratory-based data have shown the ability of toluene (Tol) to exacerbate noise-induced hearing loss. However, the mechanism responsible for the synergistic effects of a coexposure to noise and Tol has not yet been completely elucidated. Recent investigations in rats have focused on quantifying the anticholinergic effects of certain aromatic solvents and have demonstrated that these solvents can cancel the protective role played by the middle-ear reflex (MER). Voltage-dependent Ca(2+) channels (VDCCs) regulate acetylcholine release in the central synaptic network and control muscular excitation/contraction processes as well. In order to identify the prevailing action of Tol in the central or peripheral compartment of the MER arc, two VDCC antagonists were injected into the common carotid trunk: omega-conotoxin MVIIC, which blocks only the neuronal N- and P/Q-type Ca(2+) channels, or verapamil, which inhibits the muscular L-type Ca(2+) channels. Rats were also implanted with an electrode on the round window membrane to measure the cochlear microphonic potential (CMP) elicited with a band noise centered at 4 kHz and emitted at 85 dB sound pressure level. The variations in CMP recorded during the test compound injection showed that Tol has similar effects to those induced by omega-conotoxin, the neuronal VDCC blocker. The response obtained with the verapamil injection was broader than those obtained with Tol or conotoxin. This investigation therefore revealed that Tol can mimic the effects of VDCC blockers. The antagonist effects of Tol would be closer to neuronal than to muscular blockers and would be presumably located at the level of the integrator centers of the reflex.

[The rhinogenic deafness and SPA therapy: clinical-experimental study]. / Sordità rinogena e terapia termale: studio clinico-sperimentale.

OBJECTIVES: The sulphur SPA inhalation therapy is useful in respiratory and otolaryngologic chronic inflammatory diseases in adult subjects and children. The therapeutic action relies on anti-inflammatory, mucolytic and trophic effects. Particularly in children, the sulphur SPA inhalation therapy, using endotympanic ventilation or Politzer method, would be suitable in the treatment of the rhinogenic deafness. Several reports have demonstrated the effectiveness of endotympanic ventilation while the results on the Politzer method are inconclusive. On the basis of these considerations, aim of our study was to analyze the effectiveness and the safety of the aerosol+Politzer with a sulphur mineral water in children affected by rhinogenic deafness or chronic inflammatory processes responsible for the onset or persistence of rhinogenic deafness. PATIENTS AND METHODS: The study has been performed on 23 subjects in pediatric age (61% women and 39% males; mean age: 6+/-2.4 years; age range: 3-14 years) affected by chronic catarrhalis otitis, chronic rhino-pharyngitis inflammations, chronic or recurrent adenoiditis with dysfunction of the Eustachian Tube. The investigated subjects underwent 12 consecutive days sulphur SPA inhalation therapy (aerosol+Politzer) at the Terme of Stabia in Castellammare (Naples, Italy). At the beginning and at the end of the SPA cycle the functionality of the middle ear and the tolerability were evaluated. RESULTS: The results have shown an increase of the impedance curves that correspond to the normal ventilation of the tympanic box (type A (13% before therapy and of 57% post-therapy) and a decrease of the pathological curves of type B and type C (87% pre-therapy and of 43% post-therapy); a significant increase of compliance (p 0.05) in pathological curves of type B and C. No adverse reaction to the SPA inhalation therapy has been reported during the study. CONCLUSIONS: In concordance with the literature our data demonstrated that the sulphur SPA inhalation treatment induce a improvement of middle ear function of the subjects examined with good local and systemic tolerability.

Effects of anesthesia on DPOAE level and phase in rats.

Many studies of the auditory system are performed on animals under general anesthesia. A concern for researchers is that these agents may significantly alter the underlying neurophysiologic mechanisms being studied. The effects may very across species, and even among individuals within a species. An investigation was undertaken to study whether DPOAE measures differ using three different anesthetic regimens: acetylpromazine-ketamine, xylazine-ketamine, and sodium pentobarbital. The same rat was anesthetized in three consecutive weeks using a different anesthetic regimen each week. DPOAE magnitude and phase temporal responses were recorded from which several measures were taken: DPOAE levels at the onset of the primaries, changes in DPOAE level as a function of time during presentation of the primaries (DeltaLI) and changes in DPOAE level (DeltaLC) and phase (DeltaPC) during presentation of a broad-band noise presented contralateral to the probe. Each week the same measurements were repeated with the rat anesthetized using a different regimen and at the end of the third week, the middle ear muscles were sectioned and the measurements repeated once again. Results showed that the anesthetic regimens did not differentially alter the DPOAE onset levels. When sodium pentobarbital was used as the anesthetic regimen, DeltaLC and DeltaPC were significantly smaller relative to those measured when the rats were anesthetized with acetylpromazine-ketamine and xylazine-ketamine. Based on the assumption that large, positive (DeltaPC) values are related to middle ear muscle activation, the middle ear muscle reflex remained at least partially active in some rats under sodium pentobarbital anesthesia. The DeltaLI measures were significantly smaller when the animals were anesthetized with xylazine-ketamine and sodium pentobarbital than when they were anesthetized with acetylpromazine-ketamine. Recordings taken after sectioning the middle ear muscles suggested that the middle ear muscle reflex substantially contributes to DeltaLC and DeltaPC measures under the anesthetic regimens xylazine-ketamine and acetylpromazine-ketamine. Data indicated that anesthetic agents variably alter neurophysiologic mechanisms involved with the complex control of the auditory signal even among individuals in the same species. Extreme care should be taken when comparing DeltaLI, DeltaLC and DeltaPC across studies when different anesthetic regimens are used within and across species.

Clear Tinnitus, middle-ear pressure, and tinnitus relief: a prospective trial.

GOAL: Our goal was to establish the efficacy, in a 12-week period, of Clear Tinnitus for tinnitus relief in patients with tinnitus of the severe, disabling type. HYPOTHESIS: We hypothesized that tinnitus relief with Clear Tinnitus reflects improvement in the sensory component of the tinnitus complaint by controlling the factor of aeration of the middle ears and improving eustachian tube function. METHOD: In a prospective clinical trial of a homeopathic preparation--Clear Tinnitus--we attempted to identify in 15 tinnitus patients (14 male, 1 female; mean age, 47.6 years) its clinical efficacy for establishing tinnitus relief for a 3-month period. We employed a descriptive data analysis method across dimensions of risk to evaluate a base of multidimensional evidence and establish support for our hypothesis. A medical-audiological tinnitus patient protocol completed by each patient identified the clinical type of tinnitus as predominantly cochlear, with a central and middle-ear component bilaterally. We identified fluctuation in middle-ear pressure (MEP) via patients' clinical history, supported by physical examination and established with tympanometry, as a factor influencing the clinical course of the tinnitus in each patient. RESULTS: Eleven of 15 patients completed the study. Seven responders reported tinnitus relief; four did not respond. Descriptive data analysis failed to detect any trends in a change in response with audiometric tests across the hearing spectrum; thus, we could derive no coefficients of hearing change. Evaluation revealed high-frequency tinnitus in 11 patients. The Feldmann masking curve comparison at the start and end of the study showed no significant change in the 11 patients. There was no significant alteration in the minimum masking levels or loudness discomfort levels before and after the study. Tympanometry and MEP measurement indicated a significant difference in MEP with an improvement on average of -58.18 in the right ear and -40.90 in the left ear for the 11 patients. Quantitative electroencephalography analysis revealed a marked difference in the number of significant abnormal recordings between the different frequency bands, with the delta band significantly higher than the theta, alpha, and beta bands for both the overall cohort of patients (n = 11) and those reporting tinnitus relief (n = 7). The tinnitus outcome questionnaires--the tinnitus intensity index, the tinnitus annoyance index, and the tinnitus reaction questionnaire--revealed a significant difference for the patients (7 of 11) obtaining tinnitus relief. Results of the tinnitus stress test, the tinnitus handicap index, and the measurement of depression scale before and after the study were not statistically significant. CONCLUSIONS: Patients who completed the study demonstrated with tympanometry a statistical and clinical significance in MEP improvement or maintenance of MEP (or both). Patients with tinnitus of the severe disabling type selected for this study and responding to Clear Tinnitus reported tinnitus relief accompanied by improvement in or maintenance of MEP of the middle ears. The statistical and clinical significance of Clear Tinnitus for establishing tinnitus relief remains to be established with a larger cohort of tinnitus patients.

Safety of ofloxacin (OFLX) and fosfomycin sodium (FOM) ear drops.

OBJECTIVE: The objective of this study is to evaluate the safety of two ear drops, Ofloxacin (OFLX: Taribid Otic Solution, Daiichi Seiyaku) and Fosfomycin sodium (FOM: Fosmicin S, Meiji Seiyaku). METHODS: Albino guinea pigs were used as experimental animals, and the ototoxicity was evaluated by means of threshold changes in the compound action potentials (CAP), when topically applied to the middle ear cavity of the guinea pig. The sound stimuli applied were; click sound, with tone bursts of 8 kHz, 4 kHz, and 2 kHz. In one group of animals, after one application of the ear drops in the right middle ear cavity, the change in CAP was compared with a contralateral saline control at 24h, one week, and four weeks. In other group of animals, the ear drops were applied into the middle ear cavity for seven consecutive days and the CAP was measured at 24h. RESULTS: At 24h the CAP threshold for click, 8 and 4 kHz elevated significantly for both the saline and ear drop treatment, but the threshold returned to normal when measured at 7 days and 28 days. Seven consecutive days of ear drops administration resulted in no reduction in the CAP for either ear drops. CONCLUSIONS: Based on the lack of changes in the CAP, these two ear drops studied did not show any significant ototoxicities.

An animal model based on the Sprague Dawley rat for the evaluation of ototoxicity.

Various methodological approaches that can be used to detect ototoxic effects caused by the administration of various substances are presented, using the Sprague-Dawley rat as an animal model. Electrophysiological data are also presented to show how the model behaves with potentially ototoxic (hyaluronic acid) and initially inert (hydroxy-propyl-methyl-cellulose) substances.

Middle-ear disease in children exposed prenatally to polychlorinated biphenyls and polychlorinated dibenzofurans.

During 1978 and 1979, an episode of poisoning from ingestion of rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans occurred in central Taiwan. We followed-up children who had been born between June 1978 and March 1985, as well as matched unexposed children. The mothers of exposed children had consumed contaminated oils before the children were born. In 1993, otolaryngologists examined the middle ear of each child with a pneumatic otoscope, and they measured the middle-ear pressure by tympanometry with a Rion RS20 impedance audiometer. The exposed children had a significantly higher prevalence of middle-ear diseases than their matched controls. The exposed children who had ear diseases had higher serum levels of 2,3,4,7,8-pentachloro- and 1,2,3,4,7,8-hexachloro-dibenzofurans than the children who did not have similar diseases. Therefore, in this study, children exposed to polychlorinated biphenyls and polychlorinated dibenzofurans had a higher incidence of middle-ear diseases than their controls.

The herbal medicine, sairei-to, enhances the mucociliary activity of the tubotympanum in the healthy guinea pig.

Mucociliary dysfunction in the tubotympanum is deeply reflected in the clinical manifestations of otitis media with effusion (OME), and clinical application of pharmacological agents with ciliostimulatory action might therefore enhance the mucociliary clearance function of the tubotympanum to more effectively eliminate middle ear effusions to the pharynx. A herbal medicine, sairei-to, enhances the in vitro ciliary activity of the middle ear during culture. However, this ciliostimulatory effect is not always applicable to the mucociliary system in situ, which may be deteriorated following oral administration of sairei-to. The present study therefore aimed at investigating the in vivo effect of sairei-to on the mucociliary system in the tubotympanum of the guinea pig. Thirty healthy guinea pigs were used. Ten animals were treated with oral administration of physiologic saline solution for 14 successive days. The remaining animals were treated with oral administration of 120 or 600 mg/kg body weight of sairei-to for 14 successive days. Each animal was used for examination of the ciliary activity and mucociliary clearance time of the tubotympanum, 24 h after the final treatment. No significant changes in either ciliary activity or mucociliary clearance time of the tubotympanum were observed upon administration of 120 mg/kg of sairei-to, which was equivalent to the clinical human dosage. By contrast, oral administration of 600 mg/kg of sairei-to significantly enhanced the ciliary activity, but failed to significantly accelerate mucociliary clearance in the tubotympanum, although the mean value of the clearance time became shorter. Therefore, our results suggest that sairei-to to some extent stimulates the function of the mucociliary system. In conclusion, the herbal medicine, sairei-to, might be useful in the treatment of OME, and preventive administration of this drug may be a new therapy in the treatment of recurrent OME.

Increase of Cl- secretion induced by Kampo medicine (Japanese herbal medicine), Sai-rei-to, in Mongolian gerbil middle ear epithelium.

Sai-rei-to, a type of Kampo medicine (Japanese herbal medicine), has been shown to be clinically effective in treating patients with otitis media with effusion. The effect of Sai-rei-to on the ion transport of the middle ear surface epithelium cultured from the Mongolian gerbil was investigated by using an Ussing chamber. Application of Sai-rei-to to the mucosal bath but not the serosal bath induced an increase in the short-circuit current (I(SC)) in the basal state. The increase in I(SC) was almost completely inhibited by addition of diphenylamine-2-carboxylic acid but not by amiloride, indicating enhancement of Cl- secretion. On the basis of the lack of changes in the intracellular Ca2+ concentration and a sideness of action, the effect of Sai-rei-to on I(SC) is thought to be a direct and selective activation on the apical Cl- channel.

Ibuprofen inhibits localized bone resorption in the middle ear.

Localized osteoclastic bone resorption plays a significant role in the pathogenesis of several diseases of the middle ear as well as orthodontic tooth movement and long bone remodeling. The mechanisms of control of localized bone loss and systemic bone resorption may be different but both may be mediated by a final common pathway which includes prostaglandins. Prostaglandins seem to have a predominantly stimulatory effect on bone resorption, although the exact mechanism is poorly understood. Ibuprofen, a nonsteroidal antiinflammatory drug, is known to inhibit the synthesis of prostaglandins. It is likely that ibuprofen, through its inhibition of prostaglandin synthesis, would decrease the localized osteoclastic bone resorption in a previously described animal model system. Mongolian gerbils were divided into three groups: low dose ibuprofen (10 mg/kg per day), high dose ibuprofen (30 mg/kg per day), and a control group. Following surgical implantation of catheters to the right bullae of each gerbil, pressure was applied for 8 days, stimulating osteoclastic bone resorption. After killing the animals and histomorphometric analysis of the bullae from each, comparisons were made between each group using osteoclast surface (percentage of bone area covered by osteoclasts), osteoclast number (number of osteoclasts/mm bone length), and osteoclast profile area (in microns2). Significantly lower osteoclast surface (Oc.S/BS) was found in pressurized bullae from both treatment groups when compared with pressurized bullae from controls (P less than 0.05) and significantly lower osteoclast number (N.Oc/T.L) in pressurized bullae from both treatment groups when compared with pressurized bullae from controls (P less than 0.05). These differences were found to be dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)