Thickening of sphenoid sinus mucosa during the acute stage of pituitary apoplexy.

The authors treated two patients with pituitary apoplexy in whom magnetic resonance (MR) images were obtained before and after the episode. Two days after the apoplectic episodes, MR imaging demonstrated marked thickening of the mucosa of the sphenoid sinus that was absent in the previous studies. The relevance of this change in the sphenoid sinus was investigated. Retrospective evaluations were performed using MR images obtained in 14 consecutive patients with classic pituitary apoplexy characterized by acute onset of severe headache. The mucosa of the sphenoid sinus had thickened predominantly in the compartment just beneath the sella turcica, in nine of 11 patients, as ascertained on MR images obtained within 7 days after the onset of apoplectic symptoms. This condition improved spontaneously in all four patients who did not undergo transsphenoidal surgery. The sphenoid sinus mucosa appeared to be normal on MR images obtained from three patients at the chronic stage (> 3 months after onset). The incidence of sphenoid sinus mucosal thickening during the acute stage was significantly higher in the patients with apoplexy than that in the 100 patients without apoplexy. A histological study conducted in four patients who underwent transsphenoidal surgery during the early stage showed that the subepithelial layer of the sphenoid sinus mucous membrane was obviously swollen. The sphenoid sinus mucosa thickens during the acute stage of pituitary apoplexy. This thickening neither indicates infectious sinusitis nor rules out the choice of the transsphenoidal route for surgery.

Functional role of nitric oxide in the nasal mucosa of the guinea pig after instillation with lipopolysaccharide.

Nitric oxide (NO) has been found to have various actions in the body. Recently, considerable attention has been focused on the intimate relationship between the intracellular production of NO and morphological or functional changes in ciliated cells. The aim of this study was to clarify the functional significance of NO in the nasal mucosa. Healthy, adult, pigmented guinea pigs were randomly divided into one control and three experimental groups. The animals were instilled with either lipopolysaccharide (LPS) only or LPS plus dexamethasone or NG-nitro L-arginine methyl ester (L-NAME). The effect of NO on the nasal epithelium was analyzed morphologically by scanning electron microscopy and physiologically by ciliary beat frequency (CBF) measurement. The origin of NO was also investigated using a fluorescent indicator for NO, namely 4,5-diaminofluorescein diacetate. LPS induced damage of cilia 3 days after the first instillation, while dexamethasone or L-NAME seemed to attenuate the effect of LPS. NO production was localized in ciliated cells and the main source of NO in ciliated cells is suggested to be inducible NO synthase. The greater number of ciliated cells of LPS-treated animals produced a larger amount of NO compared with normal animals. LPS also induced a decrease in CBF, which was inhibited by dexamethasone or L-NAME. It is suggested that NO may play an important role in pathological changes in the nasal mucosa.

Increased nitric oxide production in nasal epithelial cells from allergic patients--RT-PCR analysis and direct imaging by a fluorescence indicator: DAF-2 DA.

BACKGROUND: Nitric oxide (NO) is believed to participate in the regulation of airway clearance and non-specific cellular immunity. Recent studies have suggested that airway epithelial cells of allergic and non-allergic individuals may differ in their ability to produce this molecule. OBJECTIVE: The aim of this study was to detect the difference in NO production in human nasal epithelial cells between normal subjects and patients with perennial allergic rhinitis (AR), and to assess the relationship between the expression of nitric oxide synthase (NOS) isoforms and the severity of the disease. METHODS: Nasal epithelial cells were obtained from the inferior turbinate. The expression of mRNAs encoding constitutive endothelial NOS (eNOS) and inducible NOS (iNOS) was studied by reverse transcription-polymerase chain reaction (RT-PCR). Direct NO production in living cells was visualized and quantified by a fluorescent indicator, DAF-2 DA. RESULTS: RT-PCR analysis demonstrated that AR patients with a RAST score of 5 or 6 showed significant increases in the levels of iNOS mRNA and slight reductions in those of eNOS mRNA. Patients with a RAST score of 2-4 also revealed the same tendency however, the difference was not significant. DAF-2 DA imaging demonstrated that epithelial cells, especially the ciliated cells, produced a larger amount of NO than non-epithelial inflammatory cells. Preincubation with L-NAME resulted in an approximate 40% decrease in both groups. CONCLUSION: These results directly indicate that nasal epithelial cells of AR patients overall produce higher levels of NO through the concomitant expression of different NOS isoforms. Continuous NO production by the epithelial cells in normal subjects further support the hypothesis that NO derived from epithelium may play dual roles in the regulation of nasal airway clearance and in the host defense. In addition, the use of DAF-2 DA provides a reliable method to visualize and quantify the direct NO production of living cells.

Effect of JTH-601, a putative alpha(1L)-adrenoceptor antagonist, on guinea pig nasal mucosa vasculature.

The existence of alpha(1)-adrenoceptors with low affinity for prazosin, an alpha(1L) subtype, has been proposed in addition to alpha(1)-adrenoceptor subtypes with high affinity for prazosin, i.e. the alpha(1H) group: alpha(1A), alpha(1B) and alpha(1D) subtypes. In the present study, we investigated the effect of JTH-601 (3-(N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminomethyl)-4-methoxy-2,5,6-trimethylphenol hemifumarate), a putative alpha(1L)-adrenoceptor antagonist, on the isolated guinea pig nasal mucosa vasculature. JTH-601 (0.01-0.03 microM) competitively antagonized the noradrenaline-induced contraction of the tissue in a concentration-dependent manner. The pA(2) value for JTH-601 was 8.14 +/- 0.04 (means +/- SEM, n = 6). The data suggests that the alpha(1L)-subtype is involved in the noradrenaline-induced contraction of the guinea pig nasal mucosa vasculature.

Analysis of local cytokine gene expression in patients with allergic rhinitis treated with CO2 laser surgery.

OBJECTIVES/HYPOTHESIS: Laser surgery of the inferior turbinates has become a popular surgical treatment for patients with allergic rhinitis, particularly for those who have persistent nasal obstruction and do not respond well to pharmacological therapy. The aim of this study was to investigate the effects of the laser surgery on local cytokine gene expression at the mucosal surface in relation to the improvement of nasal symptoms. STUDY DESIGN: A prospective analysis of 25 patients with allergic rhinitis caused by the house dust mite who underwent laser surgery twice with a 1-month interval on an outpatient basis. Fifteen healthy volunteers served as normal control subjects. METHODS: Improvement of the nasal symptoms was evaluated on a graded scale. Nasal mucosal cells were obtained by brushing from the inferior turbinate at each visit. The expression of messenger RNA (mRNA) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, RANTES (regulated on activation, normal T-cell expressed and secreted), and eotaxin was semiquantitatively analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Two months after treatment, the nasal symptom scores significantly decreased from baseline. The decrease was most apparent in nasal obstruction. RT-PCR analysis revealed that a significant decrease in IL-8 and RANTES expression (P < .001 and P = .012, respectively) was observed after successive laser treatment, and the reduction in these cytokines was significantly correlated. On the other hand, mRNA expression of GM-CSF, IL-6, and eotaxin remained unchanged. CONCLUSIONS: This study provided evidence that the expression of local inflammatory cytokines can be attenuated in part by CO2 laser treatment, which may be closely related to the clinical effectiveness of this procedure.

Modulation of ciliary activity by tumor necrosis factor-alpha in cultured sinus epithelial cells. Possible roles of nitric oxide.

The primary function of well-differentiated ciliated epithelium in the paranasal sinus is to eliminate harmful agents through the beating action of cilia. Respiratory epithelium also contributes to local inflammatory processes through the release of various proinflammatory cytokines. Recently, considerable attention has been focused on the intimate relationship between the cytokine-dependent regulation of the ciliary beat frequency (CBF) and intra-cellular production of nitric oxide (NO) in ciliated epithelial cells. The aims of this study are to examine the effect of tumor necrosis factor-alpha (TNF-alpha), one of the major proinflammatory cytokines, on the ciliary activity of human sinus epithelial cells and to assess the hypothesis that NO is involved in this regulatory mechanism. Human maxillary or ethmoidal sinus mucosa (n = 23) were cultured by the explant-outgrowth method. CBF of the outgrowth ciliated cells was measured by the photoelectrical method before and after being treated with TNF-alpha (0.1, 1 and 10 ng/ml) or dexamethasone (10(-6) M and 10(-7) M). We also investigated the expression of nitric oxide synthase (NOS) isoforms, enzymes responsible for NO synthesis, by fluorescent immunohistochemistry. TNF-alpha increased CBF at relatively low concentrations (0.1 and 1 ng/ml) and decreased CBF at a high concentration (10 ng/ml). Dexamethasone decreased CBF at a concentration of 10(-6) M. Fluorescent immunohistochemistry demonstrated that the expression of inducible NOS was augmented by TNF-alpha and attenuated by dexamethasone, whereas that of endothelial NOS remained unchanged. We conclude that human sinus epithelial cells potentially contribute to the inflammatory process by regulating their ciliary motility through an NO-dependent pathway. Proinflammatory cytokines and steroids are able to modulate this mechanism by the induction or inhibition of expression of different NOS isoforms.

Expression of drug resistance-related genes in head and neck squamous cell carcinomas and normal mucosa.

We examined the expression levels of mRNA for multidrug resistance 1 (MDR1), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT), lung resistance-related protein (LRP), topoisomerase IIalpha, beta (Topo IIalpha, beta) and topoisomerase I (Topo I) genes in human head and neck squamous cell carcinoma (HNSCC) specimens and mucosa (HNM) specimens, to elucidate their roles in relation to the biological characteristics and drug resistance in vivo. Fifty-eight samples (45 head and neck carcinomas and 13 head and neck mucosa) obtained during surgical resection or biopsy from 38 patients were analyzed using the quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. MDR1, MRP, LRP, Topo IIalpha, Topo IIbeta, and Topo I gene transcripts were detected in all the samples tested, but cMOAT mRNA was not detected in them. Comparisons of the expression levels in HNSCC with those in HNM showed that the Topo IIalpha gene expression level was higher in HNSCC than in HNM (P=0.0298). Moreover, the Topo IIalpha mRNA level was significantly higher in metastatic lymph node samples of HNSCC than in HNM samples (P=0.0205). There were no significant differences in the six genes' expression levels between samples exposed to platinum drugs and those not exposed to platinum drugs. These results suggest that it may be effective in anticancer therapy to use topoisomerase-targetting drugs against HNSCC, especially metastatic neck tumors, and that the expression of these genes in HNSCC is not associated with platinum drug exposure.

Effect of 9-cis-retinoic acid on oral squamous cell carcinoma cell lines.

Retinoic acid (RA) has been shown to be effective in suppressing premalignant lesions and preventing second primary malignancies in patients cured of squamous cell carcinoma of the head and neck. However, the precise mechanisms of these effects are still uncertain. In the present study, we examined the effect of 9-cis-RA on the growth of six oral cancer cell lines (HSC-2, HSC-3, HSC-4, Ca9-22, Ho-1-N-1 and Ho-1-u-1). In addition, the relationship among growth and differentiation of tumor cells, RA responsiveness and the expression of nuclear retinoic acid receptors were also investigated. Among the six cell lines examined, five (HSC-2, HSC-3, HSC-4, Ca9-22 and Ho-1-u-1) displayed growth inhibition after treatment with 1x10(-6) M 9-cis-RA, while Ho-1-N-1 cells were resistant to 9-cis-RA. The expression level of RARbeta in 9-cis-RA resistant Ho-1-N-1 cells was very low in comparison with the sensitive cell lines. On the other hand, all of the six the cell lines expressed RARalpha, RARgamma, and RXRalpha at various levels. 9-cis-RA induced accumulation of cell population in G1 phase in HSC-3 cells on the 6th day of the treatment, followed by a marked reduction in the levels of hyperphosphorylated pRB, whereas p53 level was not altered. Interestingly, 9-cis-RA induced transiently the expression of p21(Waf1/Cip1), p27(Kip1), p300, CBP, BAX, Bak and bcl-2 proteins, respectively. This effect was associated with reduction of cyclin D1, cdk4 and CDK-activating kinase (cyclin H and cdk7) protein in HSC-3 cells. These results suggest that the growth inhibitory effect of 9-cis-RA on oral squamous cell carcinoma may depend on the expression levels of RARs, especially RARbeta proteins and RXRalpha proteins, and that 9-cis-RA may provide a powerful therapeutic agent for head and neck cancers.

alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature.

It is now clear that alpha(1)-adrenoceptors comprise a heterogeneous family. In the present study, we characterized the alpha(1)-adrenoceptor subtype in the nasal mucosa vasculature of guinea pigs. A rectangular strip of guinea pig nasal mucosa was suspended in an organ bath containing Krebs' bicarbonate solution. Changes in tension were recorded isometrically. Concentration-response curves for agonists were obtained in a cumulative manner. Noradrenaline produced the greatest contraction of the nasal mucosa vasculature. NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride) and oxymetazoline worked as partial agonists. The intrinsic activities of NS-49 and oxymetazoline were 0.50+/-0.22 and 0.29+/-0.17, respectively, compared with noradrenaline (=1.00). Prazosin and the putative alpha(1A)-adrenoceptor antagonists WB-4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane) and 5-methylurapidil antagonized the response to noradrenaline competitively (pA(2) for prazosin<9.0). Conversely, putative alpha(1B) and alpha(1D)-adrenoceptor antagonists (spiperone and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4, 5]decane-7,9-dione), respectively) did not antagonize competitively. These results suggest that the alpha(1A)-subtype is predominant and that the alpha(1L) (or alpha(1N)) subtype may also be present in the guinea pig nasal mucosa vasculature. Furthermore, NS-49 might prove to be a nasal mucosa vasoconstrictor, which will improve nasal obstruction.

Effect of hydrogen peroxide on guinea pig nasal mucosa vasculature.

The effect of hydrogen peroxide (H2O2) on guinea pig nasal mucosa vasculature was studied by in vitro assay. H2O2 elicited relaxation of guinea pig nasal mucosa strips precontracted with phenylephrine in a concentration-dependent manner. The relaxant response to H2O2 was abolished in the presence of catalase. Preincubation of the strips with N(G)-nitro-L-arginine methyl ester or methylene blue significantly attenuated the relaxant responses elicited by H2O2. Fluorescence caused by DAF-2 DA, a fluorescence indicator for nitric oxide, was observed along the nasal mucosa vasculature in response to H2O2. These results suggest that H2O2 induced relaxation of the guinea pig nasal mucosa vasculature and that this relaxation is mediated by the NO/cGMP pathway.

Increased expression of inducible nitric oxide synthase in nasal epithelial cells in patients with allergic rhinitis.

OBJECTIVES: Although ciliated epithelial cells of human nose and paranasal sinuses have recently been reported to be the major source of locally detected nitric oxide (NO), changes to the NO production by these cells and their functional roles remain uncertain in relation to allergic rhinitis. The objective of this study is to investigate differences in the ability of induction of nitric oxide synthase (NOS) isoforms by nasal epithelial cells. STUDY DESIGN: Epithelial cells of the inferior turbinate taken from 12 normal subjects and 12 allergic patients against house dust mite were used. Samples from the house dust group were taken both before and after antigen provocation. METHODS: Immunoreactivity for two NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), was examined by the laser scanning confocal microscope. The labeled cells were processed into digital images, and the fluorescence intensity was assessed quantitatively. RESULTS: The degree of iNOS expression of the epithelial cells was significantly elevated in the house dust group compared with that of the control group. The expression appeared identical both before and after antigen provocation in the house dust group. On the other hand, there was no significant difference in eNOS expression between the two groups. CONCLUSIONS: We assume that the increased iNOS expression of the epithelial cells in the house dust group might result from stimulated secretion of proinflammatory cytokines during allergic responses. This further suggests profound contribution of nasal epithelial cells to modifying the airway clearance through the production of high levels of NO.

Cholinergic and glutamatergic transmission in medial vestibular nucleus neurons responding to lateral roll tilt in rats.

The responses of the medial vestibular nucleus (MVN) neurons to lateral tilt and the neurotransmitters mediating otolith information to MVN neurons were investigated using rats. A computer-operated goniometer was tilted 20 degrees clockwise and counterclockwise at an angular speed of 5 degrees /s and paused in the inclined positions for 10 s to record neuronal responses in the static phase. The 185 MVN neurons recorded were classified into eight types according to their responses to tilt (alpha, beta, gamma, delta, epsilon, zeta, eta and theta). A majority showed increased firing in response to ipsilateral tilting and decreased firing in response to contralateral tilting (alpha type: 31.4%) or exhibited the reverse pattern (beta type: 36.8%). Further, other groups of neurons increased (gamma type) or decreased (delta type) firing rates to either side tilting and increased (epsilon and zeta type) or decreased (eta and theta type) firing only on one side. Atropine or L-glutamic acid diethyl ester hydrochloride (GDEE) applied microiontophoretically antagonized tilt-induced firing of alpha type neurons in 58.8% or 60.0%, respectively, and of beta type neurons in 66.7% or 58.3%, respectively. When the effects of atropine and GDEE were examined in the same neurons, antagonizing effects of both drugs on tilt-induced firing were obtained in 28.6% and 40.0% of alpha and beta type neurons, respectively. These results suggest that both acetylcholine and glutamate act as neurotransmitters in the transmission of otolith information to most MVN neurons.

Cold exposure enhances nitroxidergic nerve-mediated vasodilatation in canine nasal mucosa.

We have previously reported that there is non-adrenergic, non-cholinergic (NANC) innervation in canine nasal mucosa and that the relaxation response to electrical stimulation of the NANC nerve is mainly mediated by nitric oxide (NO). In the present study, we examined the effect of cold exposure (24 degrees C) on nitroxidergic nerve-mediated vasodilatation in isolated canine nasal mucosa. Nasal mucosa strips, prepared from canine nasal septum and moderately precontracted with methoxamine in the presence of atropine and guanethidine, relaxed in response to transmural electrical stimulation (square pulses of 0.5-msec duration, at 5 Hz and 25 V). The degree of relaxation at 24 degrees C (55.4+/-13.2% of methoxamine-induced contraction, mean+/-S.D., n=6) was significantly greater than that at 34 degrees C (33.8+/-8.6%, n=6). This phenomenon was reversible. In contrast, the magnitude of relaxation responses to an NO donor (sodium nitroprusside of 0.1 and 1 microM) remained unchanged by cold exposure. These results suggest that the release of NO from the nitroxidergic nerve endings is augmented by cold exposure and, thus, vasodilatation of the nasal blood vessel is enhanced, thereby contributing to the swelling of the nasal mucosa in cold conditions.

Cytochemical and patch-clamp studies of calcium influx through voltage-dependent Ca2+ channels in vestibular supporting cells of guinea pigs.

To clarify whether or not vestibular supporting cells have voltage-dependent Ca2+ channels, cytochemical and patch-clamp studies were performed using cells isolated from the ampullae of the semicircular canal of the guinea pig. Image analysis used fura-2 as a Ca(2+)-sensitive fluorescence dye and showed that the intracellular Ca2+ concentration ([Ca2+]i) increased with bath application of high (150 mM)K+, but was unaffected by 80 mM K+. The increase in [Ca2+]i induced by high K+ was completely blocked by 1 microM nifedipine as an L-type Ca2+ channel antagonist. In the patch-clamp whole-cell recording of the isolated supporting cells, the voltage-dependent inward current was induced by a depolarizing pulse lasting 2 s in a high (50 mM) Ca2+ and tetraethylammonium-containing external solution replaced by choline chloride and a Cs(+)-containing internal solution. The inward current was obtained when the membrane was depolarized to -50 mV and maximum current was observed at -10 to +10 mV. This inward current was completely blocked by 1 microM nifedipine. These findings strongly suggest that voltage-dependent Ca2+ channels exist in the vestibular supporting cells and regulate Ca2+ concentration in the vestibular endolymph.

Calcium mobilization in isolated epithelial cells of the endolymphatic sac.

Endolymphatic sac epithelial cells were isolated from the endolymphatic sac of the guinea pig by enzymatic and mechanical dissociation. The intracellular free calcium ion concentrations ([Ca2+]i) of the isolated cells were determined using the Ca(2+)-sensitive dye fura-2. The isolated cells were classified into two types, i.e. light and dark cells. In the resting state, [Ca2+]i in the cells was variable in both types of cells. In the presence of 200 microM ATP, there was a rapid rise in [Ca2+]i. These findings suggest that endolymphatic sac epithelial cells may have receptor-mediated Ca channels which may play an important role for a nerve-mediated local feedback system of the endolymphatic sac to regulate homeostasis of endolymph volume, pressure and electrolyte balance.

Enhancement of GABA-mediated inhibition of rat medial vestibular nucleus neurons by the neurosteroid 20-hydroxyecdysone.

In vivo electrophysiological and patch-clamp studies were performed to determine whether 20-hydroxyecdysone (20-HE), a neurosteroid, influenced neuronal activities of the medial vestibular nucleus (MVN) using chloral hydrate-anesthetized rats and dissociated MVN neurons, respectively. Single neuronal activities of MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each micropipette was filled with 20-HE, glutamate, bicuculline or 2 M NaCl. These chemicals were applied microiontophoretically to the immediate vicinity of the target neurons. Microiontophoretically applied 20-HE (20-80 nA) dose-dependently decreased rotation-induced firings of both type I and II neurons, which were identified according to their responses to horizontal sinusoidal rotations. Microiontophoretically applied bicuculline, a GABAA receptor antagonist, inhibited 20-HE-induced decreases in neuronal firing of MVN. These findings suggest that 20-HE potentiates the action of GABA, probably by acting directly on the GABAA receptor of MVN neurons. In addition, microiontophoretically applied 20-HE decreased firings induced by glutamate in both type I and II neurons. This decrease by 20-HE was also antagonized with bicuculline. Furthermore, the effects of 20-HE on GABA-induced currents in acutely dissociated MVN neurons were investigated using the whole-cell patch-clamp technique. Under voltage-clamp conditions, GABA (10 microM)-induced currents were potentiated in the presence of 20-HE (100 microM). These findings suggest that 20-HE inhibits MVN neurons by acting on the modulatory site on GABA receptor-ion channel complexes to potentiate GABA inhibition.

Localization of nitric oxide synthase in human nasal mucosa with nasal allergy.

Nitric oxide (NO) plays an important role in the regulation of upper respiratory function. In the nasal cavity, the concentration of NO in the air in patients with untreated allergic rhinitis is higher than that in normal individuals. NO is produced by the action of NO synthase (NOS) using L-arginine as a substrate. To investigate the expression of NOS in human nasal mucosa, histochemical staining for NADPH diaphorase and immunohistochemical staining for NOS isoforms were carried out in nasal inferior turbinate mucosa from patients with nasal allergy. Those without nasal allergy served as controls. NADPH diaphorase histochemical study revealed that NOS was expressed in the nasal epithelium, submucosal glands, nerve fibres and the endothelium in specimens of both allergic and control groups. Immunoreactivity to endothelial NOS (eNOS) was localized to epithelial and endothelial cells in both allergic and control groups. In some specimens in both groups, nerve fibres around submucosal glands stained positively for eNOS. Immunoreactivity to eNOS, however, was slightly stronger in the epithelia of the allergic group than in those of the controls. Immunoreactivity to inducible NOS (iNOS) was localized to epithelial cells, endothelial cells, nasal glands and inflammatory cells. The staining of epithelial cells and inflammatory cells was more marked in the allergic group than the controls. These findings may suggest that the greater amounts of NO in the nasal air of patients with allergic rhinitis are mainly induced by iNOS activity.

Effect of streptomycin on the otoconial layer of the guinea pig.

The effects of streptomycin on the otoconial layer of the adult guinea pig were investigated using scanning electron microscopy. Administration of streptomycin induced a reduction of otoconia with formation of giant otoconia. These phenomena reached their maximum 4 weeks after the cessation of streptomycin intoxication in the utricle and between 2 and 6 weeks after in the saccule. Otoconia began to recover in the utricle 4 weeks and in the saccule 6 weeks after the cessation of streptomycin intoxication with an increasing number of small otoconia. Eight or 10 weeks after the cessation of streptomycin intoxication, the otoconial layer has completely recovered in both the utricle and saccule.

Formation and fate of giant otoconia of the guinea pig following streptomycin intoxication.

Formation and fate of abnormal (giant) otoconia of the guinea pig following streptomycin intoxication were investigated using scanning electron microscopy. The giant otoconia formed as multifaceted morphology in their early developmental period. They grew up the the transitional type and finally to the cylindrical type. It has been suggested that the giant otoconia found following streptomycin intoxication may be formed mainly by dissolution of normal otoconia due to the loss of environmental calcium, followed by recrystallization as giant crystals. These phenomena seemed to be closely related to the otoconial dynamics which may regulate calcium ion homeostasis of the endolymph.

Effect of streptomycin intoxication on vestibular nerve regeneration and posture recovery.

The action of streptomycin sulfate (SM) on the regenerative process of the vestibular nerve and posture recovery was studied, using bull frogs. The vestibular nerve was sectioned in various conditions with intact endorgan or with SM intoxication. When the nerve was sectioned with the hair cells left intact, the nerve regenerated well and body balance recovered to normal. However, when neural regeneration was blocked, recovery was incomplete. SM intoxication resulted in various degrees of hair cell damage. Degree of posture recovery correlated well with the number of hair cells. When the nerve was sectioned after damaging the hair cell, the nerve failed to regenerate and posture recovery was incomplete. These results suggest that the degree of posture recovery depends on hair cell function and neural regeneration. Furthermore, neural regeneration is strongly influenced by hair cell function.