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Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis.

Aims We have evaluated the sedative properties of H1-antihistamines by using positron emission tomography (PET) and 11C-doxepin. The purpose of the present study was to measure histamine H1 receptor occupancy (H1RO) of loratadine 10 mg in patients with allergic rhinitis and to compare this occupancy with that of d-chlorpheniramine 2 mg, a first-generation antihistamine. We also compared our PET findings with the proportional impairment ratio reported by McDonald et al. Methods The H1RO of loratadine 10 mg and d-chlorpheniramine 2 mg were evaluated in human brains in a double-blind and crossover design using 11C-doxepin PET. Eleven young male patients with allergic rhinitis were examined by PET following oral single administration of loratadine 10 mg and d-chlorpheniramine 2 mg. Results Loratadine 10 mg occupied 11.7 ± 19.5% of histamine H1 receptors in the cortex, whereas d-chlorpheniramine 2 mg occupied 53.0 ± 33.2% in the same area, suggesting a non-sedating property of loratadine at a dose of 10 mg. The H1RO values of loratadine and d-chlorpheniramine as well as those of previous studies were found to be significantly proportional to the proportional impairment ratio (r = 0.899). Conclusion Measurement of H1RO is a sensitive and absolute method to characterize the non-sedating property of drugs with H1 antagonistic activity. Copyright © 2011 John Wiley & Sons, Ltd.

The number of Japanese cedar and/or cypress pollinosis patients has been clearly increasing. Not only nasal symptoms but also pharyngo-symptoms impair the QOL of pollinosis patients. In this study, the correlations with coughs and the other symptoms with the QOL, were studied. Four thousand, seven hundred and sixty-five patients with seasonal allergic rhinitis were enrolled in the Osaka area as subjects in this study. Thirty-nine point nine percent of patients had a cough: 49.7% of those began to cough with pollen scattering and 33.6% of them began to cough during the pollen scattering peak period. Moreover in 52.0% of those patients with a cough, the coughing became most severe during the scattering peak. The onset of coughing showed the highest correlation with nasal obstruction and/or mouth respiration with obstruction, so it seemed that nasal obstruction participated as an exacerbating factor of the cough in pollinosis patients.

Some antihistamine drugs that are used for rhinitis and pollinosis have a sedative effect as they enter the brain and block the H1 receptor, potentially causing serious accidents. Receptor occupancy has been measured with PET under single-dose administration in humans to classify antihistamines as more sedating or as less sedating (or nonsedating). In this study, the effect of repeated administration of olopatadine, an antihistamine, on the cerebral H1 receptor was measured with PET. Methods: A total of 17 young men with rhinitis underwent dynamic brain PET with 11C-doxepin at baseline, under an initial single dose of 5 mg of olopatadine (acute scan), and under another 5-mg dose after repeated administration of olopatadine at 10 mg/d for 4 wk (chronic scan). The H1 receptor binding potential was estimated using Logan graphical analysis with cerebellum as reference region input. Results: The acute scan showed a slight decrease in H1 receptor binding potential across the cerebral cortex (by 15% in the frontal cortex), but the chronic scan showed a marked decrease (by 45% from the acute scan in the frontal cortex). Behavioral data before and after the PET scans did not reveal any sedative effect. Conclusion: The results may be interpreted as either intracerebral accumulation of olopatadine or H1 receptor downregulation due to repeated administration. The study shows feasibility and potential value for PET in evaluating the pharmacologic effect of a drug not only after a single dose but also after repeated administration.

This study demonstrates that the co-administration of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) (LPS/TNF-alpha) can induce the expression of inducible nitric oxide synthase (iNOS), which results in the generation of apoptosis in cultured human nasal microvascular endothelial cells (HNMECs). Since LPS and TNF-alpha have been suggested to play an important role in the pathophysiology of nasal disease, we conclude that microvascular leakage may therefore contribute to the inflammatory process in nasal disease, such as allergic rhinitis and asthma.The HNMECs were obtained from the inferior turbinate and subsequently cultured. The expression of iNOS induced by both the LPS and TNF-alpha was investigated by fluorescent immunohistochemistry, using confocal laser microscopy. The DNA-binding dye, Hoechist 33342, was also used to analyze the apoptosis in the HNMECs.The fluorescent immunohistochemistory study demonstrated that LPS and TNF-alpha induced the expression of iNOS in HNMECs. LPS/TNF-alpha remarkably augmented the expression of iNOS in HNMECs in comparison to stimulation by either LPS or TNF-alpha alone. LPS/TNF-alpha also induced apoptosis in HNMECs. 1400W, a highly selective inhibitor of iNOS, inhibited both the expression of iNOS and the apoptosis induced by LPS/TNF-alpha.

Olopatadine, a new second-generation antihistamine, is widely used in the treatment of allergic disorders. The low levels of histamine H1 receptor occupancy in human brain by olopatadine, which is related to its minimal sedation, suggest its low penetration into the brain. The present study evaluates the impact of P-glycoprotein (P-gp) on brain penetration and plasma concentration of olopatadine. The uptake amount of olopatadine in human P-gp transfected LLC-PK1 cells (LLC-GA5-COL150) was lower than that in LLC-PK1. The uptake of olopatadine in LLC-GA5-COL150 was increased in the same level as that in LLC-PK1 in the presence of cyclosporine A, a P-gp inhibitor. After intravenous or oral administration of olopatadine to wild type (WT) and mdr1a/1b knockout (KO) mice at a dose of 1 mg/kg, the brain concentration in KO mice was higher than that in WT mice. On the other hand, the plasma concentration of olopatadine after either route of administration was not different between WT and KO mice. These results suggest that olopatadine is a substrate of P-gp, and that P-gp limits the brain penetration but dose not affect the plasma concentration of olopatadine.

PFAPA has recently been defined as a non-hereditary autoinflammatory disease characterized by Periodic episodes of high Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis. PFAPA is a benign pediatric syndrome of unknown etiology. It might have been diagnosed as antibiotic-resistant recurrent tonsillitis and indicated for unnecessary tonsillectomy in the otolaryngology clinic. Autoinflammatory diseases are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen-specific T cells. This disease is induced by abnormality of neutrophil-related inflammatory cytokines that regulates inflammation, innate immunity and apoptosis. Up-to-date information on innate immunity is also concisely reviewed.

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca(2+)-free solution. L-N(G)-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca(2+) concentrations ([Ca(2+)](i)) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca(2+) response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca(2+)](i) increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca(2+) response via the NO-cGMP-PKG pathway by a feedback mechanism.

We performed argon plasma coagulation (APC) in 64 patients with perennial allergic rhinitis and 115 patients with cedar pollinosis, and investigated the treatment response and degree of satisfaction. With respect to various symptoms and topical findings, 87 to 89% patients with perennial allergic rhinitis responded to APC for 6 months after this therapy. One year after APC, the response rates for nasal discharge and sneezing ranged from 67% to 69%; the treatment response differed among the symptoms. The response rate for each symptom was approximately 50% 2 years after APC. An increasing number of patients required additional irradiation or other treatments between 1 year and 2 years after APC. Furthermore, 65% of the patients with cedar pollinosis responded to APC, and 77% of the patients were satisfied with this therapy.In years with higher pollen dispersion, the response rate was 52%. In years with lower pollen dispersion, the response rate was 92%. The effects on pollinosis depended on pollen dispersion. In one-third of patients who underwent APC the year before lower pollen dispersion was noted, the effects of APC were maintained over the year. When average pollen dispersion is expected, APC should be performed annually. In 18 of 21 patients with cedar pollinosis complicated by Dactylis glomerata pollinosis, the effects of APC persisted until the end of Dactylis glomerata pollen dispersion. In patients with cedar pollinosis complicated by perennial allergic rhinitis, the response rate was similar to that in patients with cedar pollinosis alone; however, satisfaction was lower. The response rate for APC during pollen dispersion was lower than that for APC prior to pollen dispersion. However, there was no difference in satisfaction. APC was useful for perennial allergic rhinitis and pollinosis.

Submucosal turbinectomy with posterior-superior nasal neurectomy has been performed for 20 patients with intractable allergic rhinitis in our institution. The operations were carried out under endonasal endoscopic observation. After the apical mucous membrane of the inferior turbinate was slightly incised and its bone was resected in the submucosa, both the posterior superior nerve and sphenopalatine artery were cut in the sphenopalatine foramen as one mass using a Harmonic scalpel. In the short-term subjective symptoms observed for 2 to 10 months, sneezing, nasal discharge, and nasal obstruction were improved to 90%, 75%, and 100%, respectively. Additionally, no surgical complications such as massive intraoperative hemorrhage, disturbance of lacrimal secretion or facial numbness were observed. Because this operation method was highly effective, was minimally invasive, and very few complications were observed, it is suggested that this is a novel surgical method for allergic rhinitis or vasomotor rhinitis.

Clinical evaluation of pre-seasonal Cot laser surgery was performed to compare pre-seasonal and seasonal administration of the antiallergic drug, Tranilast, for patients with Japanese cedar pollinosis during the cedar pollen season in 1996. Sixteen cases (the laser group) received Cot laser surgery 2-3 months before the pollen began to scatter. Seventeen cases (the Tranilast group) received Tranilast, at least 2-4 weeks before and during the scattering. In the laser group, nasal symptoms were suppressed more effectively than those of the Tranilast group throughout the pollen season. In the laser group, the rate of effectiveness was as high as 70% in patients with sneezing attacks, 56% in patients with rhinorrhea and 82% in patients with nasal obstruction, whereas the rates were 60%, 50% and 67% respectively in the Tranilast group. Comparison of the two groups for seasonal variations of cedar specific IgE antibody, the amount of plasma histamine, the number of eosinophils in the nasal smear and the response to the nasal provocation test, suggested that the allergic reaction in the inferior turbinate was inhibited by the laser surgery. Based on these results, we conclude that laser surgery was useful for the prophylactic treatment of Japanese cedar pollinosis.

The transformation of silicon from an amorphous phase to a polycrystalline phase by excimer laser annealing was investigated by means of Raman spectroscopy and electron mobility measurements. It was shown that the phase transformation was mainly governed by the energy density of the laser, and that when the density was high enough to evaporate the surface layer of the amorphous silicon, a latent state of the multiple irradiated sample was formed, where the Raman intensity exceeded that of the bulk crystal silicon and the electron mobility of the film became very high. This observation was explained by the pyramidal grain growth structure of the crystalline silicon. The amorphous component at the grain boundary was also observed in measured Raman spectra and it was shown that the presence of this phase had a significant influence on reducing the field effect mobility.

Human mucosal microvascular endothelial cells (HMMECs) were isolated and cultured from the mucosa of nasal inferior turbinates. These cells were identified by human factor-VIII antigen and UEA-I. We also investigated alterations in intracellular calcium concentration [Ca2+]i, in HMMECs using the Ca(2+)-sensitive dye fura-2. Depolarization by high K+ (150 mM) induced no changes in [Ca2+]i in HMMECs, thereby indicating the lack of voltage-dependent Ca2+ channels in these cells. Extracellular ATP increased [Ca2+]i in HMMECs both in the presence and absence of extracellular Ca2+. These results suggest that ATP may induce a release of Ca2+ from intracellular stores in HMMECs. Adenosine induced no changes in [Ca2+]i in HMMECs. It is thus likely that HMMECs obtained from the nasal inferior turbinate may carry P2-purinoceptors but not P1-purinoceptors.

Platelet-activating factor (PAF) is one of the most potent biological lipid mediators. This is especially true in relation to inflammation. In order to characterize the biochemical features of otitis media with effusion, the authors characterized and determined the concentration of the PAF present in human middle ear effusions obtained from 23 patients with otitis media with effusion. Each sample of middle ear effusion was divided into two groups: serous (n = 12) and mucoid effusions (n = 11). The platelet-activating factor activity was found mainly in mucoid middle ear effusions, and the amounts of PAF were higher in mucoid type (3.55 +/- 1.19 ng/g, mean +/- standard deviation [SD]) than in the serous type (0.44 +/- 0.19 ng/g). Phospholipids obtained from the middle ear effusions contained a large amount of lyso-platelet-activating factor, the biologically inactive precursor or breakdown product of platelet-activating factor. Based on these findings, it is suggested that platelet-activating factor may play an important role as a mediator of the inflammatory responses in the pathogenesis of otitis media with effusion.

The infralabyrinthine approach to vestibular neurectomy was performed in 9 patients with unilateral Menière's disease. According to the AAOO (1972) criteria, 7 of 9 cases were graded as class B and the remaining 2 cases as class C. Otherwise, according to the AAO-HNS (1985) criteria, 6 patients who could be followed over 2 years were all graded as 'complete' at the vertigo control. The compensation of the spontaneous vestibular signs was rapid in the first 2 postoperative weeks, though an occasional imbalance on movement persisted even 3 years after the operation. No specific caloric reaction was elicited in any patient after warm or cold water irrigation of the operated side in any postoperative period. There have been no serious complications except a delayed facial palsy that appeared in one case one week after surgery. This approach offers access to the vestibular nerve with minimal risk and morbidity.

A 4% cocaine (total dose; 200 mg) solution with 1 mg epinephrine was used as a topical anesthetic for 178 cases undergoing functional endoscopic sinus surgery. Complications were investigated before and during surgery. Bleeding amount and operative duration were compared between patients with and without topical cocaine application. Tachycardia (26 cases) was the only complication encountered in this study. Tachycardia occurred at a high incidence in cases which used atropine as a premedication. Total bleeding amount did no differ significantly between those with and without topical cocaine. However, minimum bleeding cases (less than 20 ml) were found in the cocaine group more frequently than in the non-cocaine group. Operative durations of cases with cocaine anesthesia were significantly shorter than cases without cocaine anesthesia. Those findings suggest that cocaine is effective for prevention of bleeding from micro-vessels and/or mucosal oozing, whereas bleeding from macro-vessels was not controlled by topical cocaine application. Topical cocaine anesthesia produced no major complications, even at 200 mg, in the presence of 1 mg epinephrine and when atropine use was avoided.

The clinical usefulness of long-term low-dose roxythromycin (RXM) therapy was studied in 21 patients with chronic sinusitis with the use of the X-ray mucociliary function test. Half the usual daily dose (150mg/day) of RXM was administrated for six months or longer. The symptom efficacy rates for rhinorrhea, nasal obstruction, postnasal discharge and heaviness of the head were 73.7%, 66.7%, 68.8% and 70.6%, respectively. The X-ray mucociliary function test proved that mucociliary clearance function improved and/or mucosal edema in the maxilary sinuses decreased in more than 75% of the patients after RXM treatment. These results suggest that RXM relieves on chronic sinusitis even below the MIC level and that its efficacy may be due to improvement of the mucociliary clearance function.

It has been reported that lymphoepithelial lesions (LEL), including Sjogren syndrome and benign lymphoepithelial lesions (BLEL), often change to low-grade malignant B-cell mucosa associated lymphoid tissue (MALT) lymphomas. In the patient described here BLEL changed to malignant lymphoma in both parotid glands over a 2-year interval. Surgical removal was performed because this malignant lymphoma generally resists to both chemotherapy and radiation therapies, and the prognosis is poor when the lymphoma extends outside the gland.

Several investigators have recently reported that experimental conditions in a mouse model which affect the pressure/volume ratio in the endolymphatic space increase the amount of a stainable substance in the endolymphatic sac (ES) lumen. They suggest that this stainable substance may play an important role in the regulation of pressure/volume homeostasis. The guinea pig is often used as an animal model of experimentally induced endolymphatic hydrops. In this study we interrupted the endolymphatic duct selectively in guinea pigs. The histology of the ES was studied by light microscopy at various time intervals after the operation. The amount of the stainable substance in the ES lumen on the operated side was increased for a few weeks postoperatively. This finding suggests that in the guinea pig model also the stainable substance in the ES lumen is involved in the regulation of pressure/volume homeostasis in the endolymphatic space.

The YAMIK sinus catheter, which was developed in Russia, is less difficult to use and causes fewer complications than the Proetz displacement method, the standard physical therapy procedure for chronic sinusitis. This method was used once a week for 3 consecutive weeks to treat 132 patients with chronic sinusitis. The only complication was slight nasal bleeding found during receiving negative pressure. An evaluation of subjective symptoms and objective findings showed that headache and nasal secretion were significantly diminished during and after treatment. Its remarkable effectiveness in reducing sinus pressure supports the “hydrops ex vacuo” theory as the mechanism of frontal sinusitis.

We have evaluated the sedative properties of H1-antihistamines by using positron emission tomography (PET) and ¹¹C-doxepin. The purpose of the present study was to measure histamine H1 receptor occupancy (H1RO) of loratadine 10 mg in patients with allergic rhinitis and to compare this occupancy with that of d-chlorpheniramine 2 mg, a first-generation antihistamine. We also compared our PET findings with the proportional impairment ratio reported by McDonald et al.The H1RO of loratadine 10 mg and d-chlorpheniramine 2 mg were evaluated in human brains in a double-blind and crossover design using ¹¹C-doxepin PET. Eleven young male patients with allergic rhinitis were examined by PET following oral single administration of loratadine 10 mg and d-chlorpheniramine 2 mg.Loratadine 10 mg occupied 11.7 ± 19.5% of histamine H1 receptors in the cortex, whereas d-chlorpheniramine 2 mg occupied 53.0 ± 33.2% in the same area, suggesting a non-sedating property of loratadine at a dose of 10 mg. The H1RO values of loratadine and d-chlorpheniramine as well as those of previous studies were found to be significantly proportional to the proportional impairment ratio (r = 0.899).Measurement of H1RO is a sensitive and absolute method to characterize the non-sedating property of drugs with H1 antagonistic activity.

Surgical anatomy for infralabyrinthine approach to the internal auditory canal was evaluated using human temporal bone in order to understand advantages and disadvantages of this approach. The procedure is extracranial without any damage of labyrinth. Lateral exposure of the internal auditory canal allows for easy separation of the cochlear and vestibular nerves. There are some potential problems of little importance stemming from anatomical variations, such as high jugular bulb, forward positioned sigmoid sinus and poor pneumatization of the infralabyrinthine space. This approach offers access to the eighth cranial nerve with minimal risk and morbidity.

To control the recurrence of nasal allergic symptoms, we performed revaporization with CO2 Laser beam in 27 patients with perennial nasal allergy whose nasal symptoms had been alleviated after the initial laser surgery. Revaporization was effective in 85% of the patients one month after surgery in 78% 2 years after surgery and in 64% 3 years after the revaporization. Patients with relapse within one year after surgery had little improvement in subjective symptoms, while patients with relapse later than one year after surgery responded well, and long-term results were good. No differences were found in the severity of the preoperative symptoms, RAST score, or IgE values between patients with early and with late recurrence.

Caloric responses to intracellular calcium homeostasis of vestibular hair cells isolated from the guinea pig were examined. An increase in intracellular free calcium ion concentration ([Ca2+]i) in the isolated cells was observed by direct heat stimulation. The cells, dissociated enzymatically or mechanically, were stimulated by perfusion of solution, in the temperature range of 2.2-5.2 degrees C. The [Ca2+]i was analysed using a digital imaging microscope and the Ca2+ sensitive dye, Fura-2. There was an increase in [Ca2+]i in both Types I and II vestibular hair cells with this heat stimulation. The direct thermal influence on vestibular sensory cells is discussed in relation to mechanisms involved in caloric nystagmus.

Sera obtained from patients with perennial mite nasal allergy and Japanese cedar pollinosis were examined to identify "beta receptor inhibitory factor". This was done by evaluating the inhibition of 3H-dihydroalprenolol binding to guinea pig cerebral membrane. beta receptor binding was inhibited by preincubation with sera from 8 of 44 (18.1%) perennial allergy patients, whereas sera from 2 of 41 (4.9%) controls showed this inhibition. Sera from 6 of 41 pollenosis patients (14.6%) showed this inhibitory effect in the pollen season but not in other seasons. Serum from one such patient (2.4%) demonstrated this effect both in and out of the pollen season. Sera from 2 pollenosis patients inhibited the beta receptor function not in the pollen season, but in the off season. This inhibitory effect was eliminated by immunodepletion from the positive-inhibition serum. These findings identified circulating beta receptor inhibitory factor in a limited population of patients with nasal allergy indicating the possible pathogenetic role of this factor in the disturbance of the sympathetic nerve function. This beta receptor inhibitory effect may correspond to the anti beta receptor autoantibody which Venter postulated in 1980.

Electron microscopic observations were used to study the relation between the adrenergic nerve terminal and the effector cell in the nasal mucosa of toluene diisocyanate-sensitized and non-sensitized guinea pigs. Adrenergic nerve terminals were abundantly distributed in the adventitia of arterioles, however, no synapse formation was observed in smooth muscle cells of the mesothelium, i.e., effector cells. Adrenergic nerve terminals were observed separated from smooth muscle cells of the mesothelium of the arteriole by distances of 1000 A-3000 A. Neurotransmission by the sympathetic nerve in the nasal mucosa is assumed to be by diffusion of norepinephrine (NE) or by diffusive synaptic conduction. The mechanism of sympathetic hypofunction in the nasal mucosa in nasal hypersensitivity is assumed to be as follows: Released histamine directly stimulates H-1 receptors at the sympathetic nerve terminal, leading to the release of NE. Once released, NE is not readily reabsorbed, and is gradually depleted in the sympathetic nerve terminal, leading to hypofunction of the sympathetic nerve.

During the 1980s, our view of airway hypersensitivity was altered significantly. Advances in biochemical techniques revealed involvement of several nonspecific events in nasal hyperreactivity: Autonomic dysfunction involving primary and/or secondary receptor disorders, epithelial damage by cytotoxic proteins in eosinophil, which is stimulated by inflammatory mediators, and an axonal reflex of sensory C fibers. Since 1983, we have neurobiochemically investigated the autonomic nerve dysfunction in the nasal mucosa of patients with nasal allergy and guinea pigs with experimentally-induced nasal hypersensitivity. We propose the following mechanisms as potential contributors to the disturbance of the beta receptor function in airway hyperreactivity: i) Down-regulation caused by excess endogenous norepinephrine stimulation, ii) down-regulation and uncoupling to adenylate cyclase, produced by the inflammatory mediator-induced activation of protein kinase C, iii) the action of beta receptor inhibitory factor, presumably anti beta receptor autoantibodies, and iv) dysfunction of beta receptor kinase, which is known to cause short-term desensitization of beta receptors after exposure to beta agonists. This review provides the anatomical and neurobiochemical background for the autonomic regulation and dysfunction in the nose. We also introduce our series of experiments and the above updated hypotheses of how functional disturbances of the autonomic nerve in the nasal mucosa may occur.

Effects of capsaicin on autonomic nerves in the nasal mucosa and olfactory bulb of toluene diisocyanate sensitized guinea pigs were studied using immunocytochemistry. In the nasal mucosa, substance P (SP)- and tyrosine hydroxylase (TH)-like immunoreactive (SPI and THI) fibers seemed to decrease after capsaicin application. Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibers did not show obvious alterations. In the olfactory bulb, SPI and CGRPI fibers were few and the effects of capsaicin on those fibers were difficult to evaluate. THI fibers seemed not to be affected by capsaicin. It is suggested that capsaicin affects not only sensory nerves but that it also impacts on THI sympathetic nerves in the nasal mucosa.

The long-term results of CO2 laser surgery in 45 patients with perennial allergic rhinitis were reviewed, and compared with the short-term results in 365 patients. Improvement was noted in 78% of the patients one month after laser surgery, and in 76% two years later. Symptoms of nasal blockage, sneezing and nasal discharge did not seem to be different between the short-term and long-term treatment groups. Laser surgery was more effective in younger than in older patients. The results were supported by the histological appearance of the nasal mucosa: a layer of abundant fibrous tissue was evident even 5 years after CO2 laser surgery.

The solid film of poly[(ω-methoxy)oligo(oxyethylene) methacrylate] [P(MEO)] doped with malachite green leuco hydroxide (MGLOH) or triphenylmethylalcohol (TPMOH) has been prepared as a new type of solid polymer electrolyte with controllable ionic conductivity upon photoirradiation. The ionic conductivity for P (MEO) film doped with 0.1 mol% MGLOH or 0.05 mol% TPMOH increased with UV irradiation. This suggests that the photogenerated ions act as conductive carrier in the matrix. In particular, for the TPMOH doped film, the effect of TPMOH content on the ionic conductivity change has been analyzed with the change of glass transition temperature (Tg) upon UV irradiation.

Photoinduced ionic conductivity in poly(ethylene glycol) 400 (PEG400)/malachite green leuco hydroxide (MGLOH) was analyzed with photochemical reaction of MGLOH in its matrix. The resonance structure in photogenerated cation lay in the favor of 4,4′-(dimethylamino) triphenylmethylcation (MG+) under UV irradiation. The change in the ionic conductivity was discussed with that in glass transition temperature (Tg) of the matrix on UV irradiation.

We describe the morphological changes of the endolymphatic sac following inner ear immune reactions, and we discuss the mechanisms of endolymphatic hydrops. Hartley guinea pigs were immunized with bovine type II collagen (BIIn), Keyhole limpet hemocyanin (KLH) or horseradish peroxidase (HRP), boosters and challenging antigens were injected through the stylomastoid foramen. Animals were sacrificed every few days up to 56 days after the antigen challenge. Polyethyleneimine (PEI) was used as a cationic tracer to demonstrate the location of anionic sites on the basement membrane. In the animals immunized with BIIn or HRP, mild to moderate endolymphatic hydrops, an infiltra-tion of mononuclear cells and a significant decrease of anionic charge in the sac tissue were observed in the early postimmunization stage. However, the KLH immunization group did not show remarkable tissue changes. The blood-labyrinth barrier descriminates according to size and charge barrier may control antigen transfer and macromolecular transport into the inner ear. Immune reactions in the inner ear may lead to impairment of barrier function, hyperpermeability of the vessels and malab-sorption of endolymph, and subsequently the development of endolymphatic hydrops.

Transient receptor potential vanilloid 4, the Ca 2+ -permeable cation channel has been proposed as an osmosensitive and a mechanosensitive channel. We investigated functional expression of transient receptor potential vanilloid 4 in inner hair cells, outer hair cells, and spiral ganglion neurons of the mouse cochlea. Transient receptor potential vanilloid 4 mRNA and protein were expressed in inner hair cells, outer hair cells, and spiral ganglion neurons on the basis of the findings of reverse transcriptase-polymerase chain reaction, single-cell reverse transcriptase-polymerase chain reaction, and immunohistochemistry, whereas they were negative in transient receptor potential vanilloid 4 -/- mice cochleae. Hypotonic stimulation and 4-α-phorbol 12,13-didecanoate, a transient receptor potential vanilloid 4 synthetic activator, increased the intracellular Ca 2+ concentrations in wild-type outer hair cells, whereas in transient receptor potential vanilloid 4 -/- mice, outer hair cells failed to exhibit a Ca 2+ response to both stimulations. In conclusion, transient receptor potential vanilloid 4 may function as an osmosensory and a mechanosensory receptor in the cochlea.

Donor T lymphocytes injected into the host systemic circulation were observed to infiltrate into the host endolymphatic sac in mice. These findings suggest that the endolymphatic sac, a major immune organ in the inner ear, is supplied with immunocompetent cells from the systemic circulation. This concept is consistent with clinical reports that inner ear disorders accompany certain systemic autoimmune diseases. Bone marrow transplantation to replace autoreactive immunocompetent cells with normal cells should be considered as a potential therapy for inner ear autoimmune diseases and an alternative to conventional treatments.