Ultrasound assessment, unlike clinical assessment, reflects enthesitis in patients with psoriatic arthritis.

OBJECTIVES: Enthesitis is a major musculoskeletal manifestation of psoriatic arthritis (PsA). It is conventionally assessed clinically, by the presence of tenderness, despite its low reliability. However, ultrasound (US) provides a sensitive and feasible method for evaluating enthesitis. We investigated enthesitis as assessed clinically and by US in patients with PsA. METHODS: Forty-seven patients with PsA underwent US examination of the bilateral humeral medial epicondyles and insertions of the triceps, distal quadriceps, proximal/distal patellae, Achilles tendons, and plantar fascia. These 14 entheses were also clinically evaluated by tenderness. The correspondence between US and clinical enthesitis was evaluated, as well as their associations with inflammatory markers (C-reactive protein [CRP], matrix metalloproteinase-3 [MMP-3]), disease activity indices (Disease Activity in Psoriatic Arthritis [DAPSA], Disease Activity Score 28 joints [DAS28-CRP], Psoriatic Arthritis Screening and Evaluation [PASE], Psoriasis Area Severity Index [PASI]), radiographic damage (modified Total Sharp Score [mTSS]), and functional status (health assessment questionnaire [HAQ]), and axial involvement. RESULTS: Among 47 patients with PsA, 37 and 23 had US and clinical enthesitis, respectively. US and clinical enthesitis had very low concordance (kappa coefficient 0.04), with no correlation between enthesitis counts (r=0.15, p=0.30). The US enthesitis count correlated only with the MMP-3 level (r=0.41, p=0.007), whereas the clinical enthesitis count correlated with the DAPSA, DAS28-CRP, HAQ, and PASE (r=0.50, p<0.001; r=0.44, p=0.002; r=0.41, p=0.008; r=0.54, p<0.001, respectively). CONCLUSIONS: US and clinical enthesitis are completely different entities. US enthesitis, but not clinical enthesitis, reflects inflammatory conditions.

Comparison of median nerve stiffness with and without rheumatoid arthritis by ultrasound real-time tissue elastography: A propensity score matching study.

Objectives: This study aimed to compare median nerve stiffness measured by ultrasound real-time tissue elastography in patients with and without rheumatoid arthritis (RA and non-RA groups, respectively).Methods: Altogether, 402 hands of 201 RA group and 222 hands of 111 non-RA group were included in the study. Ultrasonography was performed to evaluate the circumference, cross-sectional area (CSA) and strain ratio as an elasticity of the median nerve at the inlet level of the carpal tunnel and the proximal portion of the carpal tunnel inlet. Using propensity score matching, the difference between RA and non-RA group were analyzed.Results: After propensity score matching, 135 hands in 104 RA group and 70 non-RA group were finally analyzed. There were no significant differences in the circumference and CSA of the median nerve between the two groups. The strain ratio of the median nerve was significantly higher in RA group than in non-RA group only at the inlet of the carpal tunnel level.Conclusions: The nerve stiffness in patients with RA measured by ultrasound real-time tissue elastography was higher than without RA. Inflammatory condition of the flexor tendon and wrist joint in patients with RA may generate fibrotic changes in the median nerve.Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000015314.

Endocytosis of microperoxidase in marginal cells is mainly regulated by RhoA signaling cascade, but not by Rho-associated protein kinase, myosin light-chain kinase and myosin phosphatase.

Endocytosis plays an important role in cell function and the activation and propagation of signaling pathways. Signaling occurs on endocytic pathways and signaling endosomes, and endocytosis is subjected to high-order regulation by cellular signaling mechanisms. Marginal cells showed active endocytosis of microperoxidase (MPO) via the clathrin-independent pathway. We examined the signaling pathway that regulates MPO endocytosis in marginal cells using specific inhibitors and activators of signaling molecules. The results showed that pertussis toxin - which inhibits the ribosylation of G-protein-coupled receptor - did not affect MPO endocytosis, but Clostridium botulinum C3 toxin - which induces RhoA inactivation resulting in extracellular-signal-related kinase inactivation - inhibited MPO endocytosis. The main endocytotic pathway of MPO did not depend on the Rho-associated protein kinase molecular switch or actin/myosin motor system, but was mainly regulated by the RhoA signaling cascade.

Time course of vestibular function changes of experimental endolymphatic hydrops in guinea pigs.

OBJECTIVE: To investigate the relationship between endolymphatic hydrops and vestibular dysfunction. METHODS: 20 pigmented guinea pigs were used: 15 for a hydrops group and 5 for a sham group. Endolymphatic hydrops was produced by electrocauterization of the endolymphatic sac on the left ears. In the horizontal vestibuloocular reflex (HVOR) study, HVOR responses were recorded before and 1, 2, and 4 weeks after surgery in 9 animals of the hydrops group and 5 animals of the sham group. HVOR gain under sinusoidal rotation with a maximal head velocity of 45 degrees /s and frequencies of 0.05, 0.1, 0.2, 0.4 and 0.8 Hz was analyzed. In the nystagmus study, spontaneous nystagmus was recorded in all animals of the hydrops and the sham groups for 1 h in the dark and the maximum slow-phase velocity was measured before and 1, 2, 4 weeks after surgery. Morphological changes in the inner ear were measured light microscopically. RESULTS: In the hydrops group, the HVOR gains at all stimulation frequencies seemed to decrease 1 week after surgery and recover 2 or 4 weeks after surgery; however, there were no statistical differences among HVOR gains in any periods after surgery. The incidence of spontaneous nystagmus gradually increased after surgery and the direction and onset showed large variation. The duration of nystagmus was approximately 10 min. The degree of endolymphatic hydrops showed large variation. In the sham group, HVOR gains at all stimulation frequencies showed no statistically different change in any period after surgery. In the sham group, no animal showed spontaneous nystagmus. CONCLUSION: Experimentally induced endolymphatic hydrops seems to contribute to vestibular dysfunction to some extent. We speculated that when endolymphatic hydrops is progressing, vestibular dysfunction might occur.

Endocytosis of MPO in marginal cells is regulated by PKC, protein phosphatase, ERK and PI3-K signaling cascades, but not by PKA and MEK signaling cascades.

Endocytosis of marginal cells plays a key role in maintaining the homeostasis of endocytosis and function of the organ of Corti. How the signaling cascade is involved in the regulation of endocytosis is an important issue at present. To investigate the regulation of endocytosis in marginal cells of the stria vascularis by the signaling network, we perfused MPO, an endocytosis tracer, with PMA, OA, staurosporin, PAO, PD98059, SB20580 or wortmannin into the cochlear duct. After 30 min endolymphatic perfusion, the tissues were fixed and the distribution of MPO was examined by electron microscopy. We explored the functions of PKC, RTK, PI3-K, PTP, and PP1/2A in MPO endocytosis and defined the MPO endocytic route. MPO endocytosis was strongly dependent on PKC, ERK, PTP, PP1/2A and PI3-K signaling networks, but not on PKA and MEK signaling networks. The MPO endocytic pathways are clathrin-, GPI-AP-, and caveolae-independent.

Electrical recording of otoacoustic emission.

CONCLUSION: Otoacoustic emissions (OAEs) could be detectable as cochlear AC potentials. Spontaneous otoacoustic emissions (SOAEs) were detected either electrically or acoustically, while evoked otoacoustic emissions (EOAEs) could be detected electrically but not acoustically. OBJECTIVE: Many lines of evidence support the hypothesis that SOAEs are produced by spontaneous mechanical oscillation within the cochlea, and perhaps motile properties of the outer hair cells. If this is the case, SOAEs, emitted acoustically in the external auditory meatus, could also be recorded electrically as cochlear AC potential. EOAE is also thought to be produced by vibration of the basilar membrane, generated by the backward-traveling waves. EOAE thus seems to be detectable electrically as cochlear AC potential. In the present study, SOAE and EOAE were recorded both acoustically and electrically in the guinea pigs to examine the correlation between electrically recorded SOAE (ER-SOAE) and acoustically recorded SOAE (AR-SOAE). In addition, a microphonics response (MPR) to tone pip was recorded to analyze the characteristics of the non-linear component and linear component of the AC responses. RESULTS: (1) In 4 out of 20 guinea pigs (20%), SOAE could be detected both acoustically and electrically. (2) Electrical signals of SOAE had a better S/N ratio than acoustical signals. Generally, only some ER-SOAE could be detected acoustically. (3) Almost without exception, the prominent frequencies of multiple ER-SOAEs corresponded to the intermodulation distortion product, or harmonics. (4) ER-SOAEs were suppressed by hypoxia or intense sound exposure and reappeared upon rebreathing or discontinuation of the external tone. During recovery, prominent frequencies showed a transient downward shift in frequency. (5) SOAEs were synchronized in phase with an external tone in the spectral neighborhood of SOAE. The averaged waveform of SOAE synchronized with the external tone was the same with either acoustic or electrical signals. (6) The MPR to tone pip is composed of two components with different frequency characteristics and input/output functions. (7) The non-linear component delayed to cochlear microphonics was markedly saturated at the intensity level of 40 dB peak equivalent SPL. This component was a phase-lock response, not a frequency-locked one. (8) The non-linear component could be separated with Probst's non-linear differential extraction technique. In the MPR to a 4-kHz tone pip, high-cut filtration at 3.5 kHz produced a waveform similar to the non-linear component separated by Probst's method.

Expression of fibroblast growth factor receptors 1-4 in human chronic tympanic membrane perforation.

OBJECTIVE: To locate fibroblast growth factor receptor (FGFRs) 1-4 in human chronic tympanic membrane (TM) perforation. METHODS: A sample of human chronic TM perforation was harvested during myringoplasty. The sample was immediately fixed in 4% paraformaldehyde and embedded in OCT compound. Immunohistochemistry was performed with FGFR 1-4 polyclonal antibodies. RESULTS: FGFRs 1-4 were strongly and weakly expressed in the epidermal and mucosal layer of the TM perforation, respectively. CONCLUSIONS: As it is impossible to perform quantitative analysis based on the fluorescence intensity of each immunoreactivity, the presence of FGFRs 1-4 in the human chronic TM perforation is shown. The expressions of FGFRs 1-4 indicated that the clinical use of bFGF agent is useful for myringoplasty.

Hormonal aspects of Ménière's disease on the basis of clinical and experimental studies.

CONCLUSIONS: Endolymph homeostasis is thought to be mediated by the vasopressin-aquaporin-2 (VP-AQP2) system in the inner ear. Endolymphatic hydrops, the morphological characteristics of Ménière's disease (MD), seems to reflect the malregulation of the VP-AQP2 system in inner ear fluid. The elevation of plasma vasopressin (p-VP) level, which is often observed in MD and its related diseases, might be one of the causative factors underlying these diseases. PURPOSE OF REVIEW: Review of the role of the VP-AQP2 system in the inner ear fluid homeostasis and in the formation and development of endolymphatic hydrops. RECENT CLINICAL AND EXPERIMENTAL FINDINGS: A clinical survey has revealed that the p-VP level is often elevated in MD and its related diseases and that the increase in the p-VP level was closely linked to vertigo attacks in MD. Experimental studies have revealed that proteins and mRNAs of aquaporin-2 and vasopressin type 2 receptor were expressed in the stria vascularis of the cochlea and the epithelium of the endolymphatic sac, and that the volume of the endolymphatic compartment was mediated by the activity of the VP-AQP2 system in the inner ear.

Effects of Glucocorticoids on the Inner Ear.

Hypothesis: Recently, several lines of evidence have suggested that the inner ear is under hormonal control. It is likely that steroids have some influence on the inner ear. Background: Many clinicians have been empirically using steroids for the treatment of diseases associated with endolymphatic hydrops. The theoretical grounds for this are not clear, and there have been a number of debates on the effectiveness of steroid treatment. Furthermore, there are few reports on histological observations of the influences of steroids on the cochlea. Method: Fifteen guinea pigs (30 ears) were divided into three groups. In the control group, physiological saline solution was administered intra-peritoneally for 3 days. In two steroid groups, 40 mg/kg/day of hydrocortisone or 4 mg/kg/day of dexamethasone was administered intra-peritoneally for 3 days. Extension of Reissner's membrane and volume change of the scala media were checked 6 h after the last administration. The degree of Reissner's membrane extension and volumetric change of the scala media were quantitatively measured with the use of a video-digitizer. Results: We did not identify any distinct changes in the cochlea of the control group. In contrast, the extension of Reissner's membrane and endolymphatic hydrops were observed in the animals in the steroid groups. Statistical analysis revealed that Reissner's membrane extended significantly in the steroid groups, and that the volume of the scala media also increased significantly. Conclusion: This is the first report to investigate the effects of systemic administration of glucocorticoids on guineapig cochlea. The extension of Reissner's membrane and dilated endolymphatic space were evident in the steroid groups. However, the underlying mechanism of histological changes was not clear, marked care needs to be taken when administering steroids to patients with Meniere's disease whose histological feature is endolymphatic hydrops.

A possible mechanism of the formation of endolymphatic hydrops and its associated inner ear disorders.

The pathology of Meniere's disease (MD) is well established to be endolymphatic hydrops. However, the mechanism underlying deafness and vertigo of MD or idiopathic endolymphatic hydrops is still unknown. In order to evaluate the pathogenesis of deafness and vertigo in MD, it seems to be rational to investigate the interrelationship between hydrops and inner ear disorders using animals with experimentally-induced endolymphatic hydrops. In spite of intense efforts by many researchers, the mechanism of vertiginous attack has been unexplained, because animals with experimental hydrops usually did not show vertiginous attack. Recently, there are two reports to succeed to evoke vertiginous attack in animals with experimental hydrops. In the present paper were first surveyed past proposals about underlying mechanism of the development of hydrops and inner ear disorders associated with hydrops, and were discussed the pathogenetic mechanism of vertiginous attack in hydrops. In conclusion, abrupt development of hydrops was thought to play a pivotal role in the onset of vertiginous seizure.

An animal model of ischemic facial palsy. Behavioral facial nerve function and ultrastructural changes of the facial nerve.

We investigated facial palsy which was induced by the interruption of the petrosal artery in guinea pigs. Forty animals were observed for 2 months regarding their behavioral facial nerve function and assessed by the blink reflex. Morphological changes in the intratemporal portion were observed with transmission electron microscopy in 20 animals with an interrupted petrosal artery. Facial palsy developed in 85.0% within 3 days after the interruption. The degree of palsy varied from mild to severe. Remission of palsy required 2-3 months in severe cases, 3 weeks or less in mild/moderate cases. Histological studies revealed a striking difference in the degree of degenerative changes between severe cases and mild/moderate cases. Animals with severe palsy showed extensive axonal atrophy and myelin disruption from the early stage. Meanwhile, degenerative changes were slight in cases with mild/moderate palsy. Regenerating unmyelinated fibers appeared 1 week after the interruption, but diminished in number 4 weeks later. Thereafter, new myelin was reformed on fibers. In cases of severe nerve damage, however, this regeneration process did not always seem to work well. A decrease in number and an irregular shape of the fibers were noted in animals with incomplete recovery. This animal model may be helpful for understanding the pathophysiology of ischemic facial palsy.

Protective effects of edaravone against ischemia-induced facial palsy.

OBJECTIVE: The protective effect of edaravone, an inhibitor of reactive oxygen species (ROS), against the development of ischemia-induced facial palsy was investigated. METHODS: Experimental ischemic facial palsy was induced by interruption of the petrosal artery (PA) in guinea pigs. The application of edaravone was carried out by daily intraperitoneal injection for 1 week. The behavioral facial movement, fluorescence intensity of ROS, and morphological changes were investigated. RESULTS: Edaravone injection from immediately after PA interruption significantly reduced dihydrotetramethylrosamine fluorescence intensity (indicative of ROS) in the facial nerve of the interrupted ear and attenuated the development of ischemia-induced facial palsy. Edaravone injection from the 2nd day following PA interruption also reduced the incidence of facial palsy. Light and electron microscopy revealed that edaravone application tended to prevent the degenerative changes of the facial nerve caused by ischemia. CONCLUSIONS: Edaravone suppressed the production of ROS and had a remarkable protective effect against the development of mild to moderate facial palsy. Morphologically, nerve damage was also decreased by edaravone injection.

Protective effect of edaravone against endolymphatic hydrops.

CONCLUSION: Our findings suggest that edaravone prevented the production of reactive oxygen species (ROS). Edaravone also delayed the formation of endolymphatic hydrops in guinea pigs, but had no effect on endolymphatic hydrops. OBJECTIVE: To analyse the protective effect of a free radical scavenger, edaravone, on endolymphatic hydrops. MATERIALS AND METHODS: Guinea pigs were subjected to surgical obliteration of the endolymphatic duct (ED). For the detection of ROS, group 1 received intraperitoneal injections of edaravone (3 mg/kg/day) for 2 days, group 2 received edaravone for 2 weeks, group 3 saline for 2 days, and group 4 saline for 2 weeks. ROS production by the organ of Corti and stria vascularis was examined by using dihydrotetramethylrosamine. For the morphological analysis, guinea pigs were divided into five groups, i.e. 2 or 4 weeks after ED obliteration, 2 weeks with edaravone, first or last 2 weeks with edaravone and sacrificed 4 weeks after ED obliteration. Increases in the ratios of the cross-sectional area of scala media were analysed quantitatively to assess the degree of endolymphatic hydrops among the above-mentioned five groups of the hydropic cochlea. RESULTS: ROS was detected both in the organ of Corti and in the lateral wall of cochleae 2 days after ED obliteration. Edaravone prevented the production of ROS and also attenuated the formation of endolymphatic hydrops in the acute hydrops group.

Isosorbide-Induced Decompression Effect on the Scala Media: Participation of Plasma Osmolality and Plasma Arginine Vasopressin.

OBJECTIVE: The correlation between the isosorbide-induced decompression effect on the endolymphatic space and plasma osmolality (p-OSM) or plasma arginine vasopressin (p-AVP) was investigated on comparing two different dosages of isosorbide (2.8 and 1.4 g/kg) to elucidate why the decompression effect is delayed with a large dose of isosorbide. MATERIALS AND METHODS: Two experiments were performed using 80 guinea pigs. Experiment 1 was designed to morphologically investigate the sequential influence of the oral intake of 1.4- and 2.8-g/kg doses of isosorbide on the endolymphatic volume. The animals used were 50 guinea pigs (control: 10, experimental: 40). All animals underwent surgical obliteration of the endolymphatic sac of the left ear. One month after the surgery, control animals were sacrificed 3 hours after the intake of distilled water, and experimental animals were sacrificed 3 and 6 hours after the isosorbide intake. All of the left temporal bone served for the quantitative assessment of changes in the endolymphatic space, and the cross-sectional area of the scala media was measured from the mid-modiolar sections of the cochlea.Experiment 2 was designed to investigate changes in p-OSM and p-AVP levels 3 hours after the oral intake of isosorbide. Animals used were 15 guinea pigs (control: 5, experimental: 10). The control group received the oral administration of distilled water (4 ml/kg), and the experimental animals were subdivided into two groups consisting of 10 animals each by the dosage of isosorbide (1.4 or 2.8 g/kg). All animals were sacrificed for the measurement of p-OSM and p-AVP concentrations 3 hours after the intake of water or 70% isosorbide solution. RESULTS: Morphologically, an isosorbide-induced decompression effect was noted in animals with both 1.4- and 2.8-g/kg doses of isosorbide. According to the regression analysis, however, the volumetric decrease of the endolymphatic space was more evident in cases with the small dose (1.4 g/kg) 3 hours after the intake (analysis of covariance [ANCOVA], p < 0.001). Six hours after, the decompression effect was significantly greater in cases with the large dose (2.8 g/kg) (ANCOVA, p < 0.001).Isosorbide intake caused a rise in p-OSM levels dose-dependently. The Cochran-Cox test revealed that the differences in the mean values among control and isosorbide groups were significant (p < 0.01). Regarding the p-AVP level, a significant increase was evident in cases with the large dose (2.8 g/kg) (p < 0.01, Cochran-Cox test), and not in cases with the small dose (1.4 g/kg). CONCLUSION: An isosorbide-induced decompression effect of the endolymphatic space was evident in spite of two different dosages of isosorbide (2.8 and 1.4 g/kg). Three hours after the isosorbide intake, however, the decompression effect was more marked in the group with the small dose (1.4 g/kg). Since significant rises in p-OSM and p-AVP were evident in the group with the large dose, this early rise of p-AVP due to dehydration seems to be the major reason for the delayed decompression effect in cases with a large isosorbide intake.

A comparison of dehydration effects of V2-antagonist (OPC-31260) on the inner ear between systemic and round window applications.

V2-antagonist (OPC-31260 (OPC)) application to the scala tympani reduced endolymphatic hydrops. In the present study, we investigated whether systemic administration or local infusion via the round window (RW application) of OPC would be more suitable for clinical use. In Experiment 1, the increase ratios of the cross-sectional area of the scala media of experimentally induced endolymphatic hydrops were quantitatively assessed among four groups of non-OPC application, RW application of xanthan gum, systemic application of OPC and RW application of OPC. In Experiment 2, the effects of systemic and RW applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM) were investigated. In Experiment 3, endocochlear DC potential (EP) was measured in guinea pigs with the RW application of OPC. Electron microscopic observations of the stria vascularis and the hair cells were also made. Both systemic and RW applications of OPC significantly reduced endolymphatic hydrops. However, systemic application resulted in the distension of the Reissner's membrane in the non-operated ear, which seemed to be caused by elevated p-VP levels resulting from the systemic application of OPC. In contrast, RW application of OPC produced no apparent toxic effects in the inner ear, as indicated electrophysiological or morphological changes. Thus, drug delivery via the round window is more useful for the clinical application of OPC for medical decompression.

Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C.

AIM: To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C (CHC). METHODS: Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group (stage 0). Twenty-five patients with sustained virological response (SVR) to interferon (IFN) therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness (LS) was performed by elastography. RESULTS: Medians (50% levels) of LS were 4.1 (3.5-4.9), 6.3 (4.8-8.5), 8.8 (6.8-12.0), 14.6 (10.5-18.6), and 22.2 (15.4-28.0), respectively, in the fibrosis stages 0-4 (P < 0.001). LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 (3.5-5.6), 5.2 (4.4-6.8), 6.8 (6.1-7.6), and 6.1 (3.6-7.9), respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type IV collagen, type IV collagen 7S, and type III procollagen N peptide. CONCLUSION: LS correlated well with the histological stage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography.

Experimental studies on the recovery processes from severe facial palsy and the development of its sequelae.

OBJECTIVE: To experimentally elucidate the pathogenesis of inappropriate co-contraction of facially innervated muscles after severe facial palsy. METHODS: Twenty-two guinea pigs with severe facial palsy induced by the interruption of the petrosal artery were used to follow up behavioral facial movement, including the degree of facial palsy and abnormal hyperkinetic facial movement of synkinesis and mass contracture. At the end of the follow-up, the evoked facial compound muscle action potential (evoked FCMP) and antidromically evoked facial nerve response (AFNR) were examined in a few typical cases with complete recovery and with incomplete recovery accompanied by synkinesis. After the follow-up, all animals were sacrificed for morphological studies, which consisted of a light-microscopic study (by Luxol fast blue and hematoxylin and eosin staining or toluidine blue staining) and/or an electron-microscopic study. RESULTS: The initial sign of recovery was mass contracture or spasm. This condition continued for 2 weeks or more. As voluntary facial movement recovered, the mass contracture became unnoticeable. It could not be distinguished when the so-called synkinesis developed. Synkinesis usually developed during the recovery process from severe to moderate palsy, and synkinesis persisted or progressed once it appeared. Histologically, unmyelinated fibers were intermingled with myelinated fibers in an early stage of recovery with mass contracture. In the late stage with the development of synkinesis, however, such an intermingling of unmyelinated and myelinated axons was not observed. In this stage, axons became well myelinated, but they were irregular in shape in cases with synkinesis. Especially, axons irregularly ran at the level of the G1 (at the region of the second genu) segment, and bifurcated axons were sporadically found. The axon count had a tendency to increase toward the periphery. AFNR was not detected, although evoked FCMP could be clearly detected in cases with synkinesis. CONCLUSION: Misguidance of regenerated axons is an important cause of facial synkinesis in the ischemia-induced facial palsy model. Ephaptic transmission between unmyelinated and myelinated axons is also likely to be responsible for mass contracture manifested in the early stage of the recovery process.

The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops.

In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic ears) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic ears, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P<0.01). However, IR-S of the OPC-infused hydropic ears (-14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P<0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.

Type 1 allergy-induced endolymphatic hydrops and the suppressive effect of H1-receptor antagonist (olopatadine hydrochloride).

OBJECTIVE: To investigate whether endolymphatic hydrops (EH) is experimentally induced by type 1 (or immediate) hypersensitivity allergic reaction and to investigate the inhibitory action of a histamine H(1)-receptor antagonist (olopatadine hydrochloride [OLO-Hy]) on allergic EH induced by systemic immune challenge with 2,4-dinitrophenylated-Ascaris (DNP-As). METHODS: The experimental animals were actively sensitized with DNP-As twice at a 4-week interval and were provoked by an injection of DNP-BSA including DNP-As 1 week after the second sensitization. The OLO-Hy (+) group received oral administration of OLO-Hy (30 mg/kg) 1 hour before the provocation, whereas the OLO-Hy (-) group received distilled water. The temporal bones in all animals were light microscopically examined to assess the degree of EH quantitatively and the expression of degranulated mast cells in the endolymphatic sac. RESULTS: Endolymphatic hydrops was observed 1, 6, 12, and 24 hours after the last sensitization in the OLO-Hy (-) group but was not observed in the OLO-Hy (+) group. Quantitative analysis of the increase ratios (IRs) of the cross-sectional area of the scala media revealed that the IRs of the OLO-Hy (-) group were significantly greater compared with those of the control group (p < 0.001). There was also a significant difference in the IRs between the OLO-Hy (-) and OLO-Hy (+) groups (p < 0.001). CONCLUSION: The systemic sensitization with DNP-As produced allergy-induced experimental EH by type 1 hypersensitivity allergic reaction, and the development of this EH was prevented by histamine H(1)-receptor antagonists.

Type 1 allergy-induced endolymphatic hydrops and the suppressive effect of leukotriene receptor antagonist.

OBJECTIVE: To investigate allergic endolymphatic hydrops (EH) and the effect of leukotriene receptor antagonist (LTRA). METHODS: Experiment 1: Thirty-six guinea pigs were actively sensitized with DNP-ascaris twice and were provoked with DNP-bovine serum albumin 1 week after the second sensitization. Alterations in the inner ear were investigated histologically at 1, 12, 24, and 36 hours after the provocation, and changes of the endolymphatic space were quantitatively assessed. The animals in the control group received no sensitization but only distilled water. Experiment 2: Twenty-four guinea pigs were actively sensitized and provoked in the same manner. Animals received oral administration of LTRA 1 hour before the provocation. Alterations in the inner ear were investigated as same manner as in Experiment 1. Experiment 3: Eleven of 19 guinea pigs were actively sensitized and provoked in the same manner. Eight animals in the control group received distilled water. One hour after these procedures, the changes in p-AVP levels were investigated. RESULTS: Experiment 1: EH was observed 12, 24, and 36 hours after the last sensitization. In these groups, their cross-sectional areas of the scala media were significantly larger than that of the control group. Degranulation of mast cells was observed in the endolymphatic sac. Experiment 2: In animal groups with LTRA, EH was not observed at all. Experiment 3: P-AVP levels were significantly elevated in animals with the sensitization. CONCLUSION: The sensitization with DNP-Ascaris produced allergic EH and elevation of p-AVP, and allergic EH was inhibited by LTRA.