Hsing Won Wang

Hypoxia enhances the stemness markers of cochlear stem/progenitor cells and expands sphere formation through activation of hypoxia-inducible factor-1alpha

Unlike neural stem cells that maintain populations in the adult brains of both rodents and humans, cochlear stem cells appear to diminish in number after birth and may become quiescent in adult mammalian cochleae. Hypoxia has been observed to promote an undifferentiated cell state in various stem cell populations; however, little is known about such an effect on cochlear stem/progenitor cells (SPCs). The aims of this study were to assess the effect of hypoxia on cochlear SPCs and to examine the impact of hypoxia-inducible factor-1 alpha (Hif-1a) on regulating such an effect. Our data demonstrate that hypoxic culturing for 24 h significantly increased sphere formation and viability of cochlear SPCs compared with those cultured under normoxic conditions. Concurrent with these proliferation promotion effects are changes in the expression of multiple stemness and cell-cycle quiescent associated gene targets, including Abcg2, nestin, p27(Kip1)and Vegf. Knockdown of Hif-1a expression by small-interfering RNA inhibited hypoxia-induced cochlear SPC expansion and resulted in downregulation of Vegf, Abcg2, and nestin and upregulation of p27(Kip1) gene expression. These results suggest that Hif-1a plays an important role in the stimulation of the proliferation of cochlear SPCs, which confers a great benefit of expanding cochlear SPCs via hypoxic conditions.

Neural stem cells secrete factors that promote auditory cell proliferation via a leukemia inhibitory factor signaling pathway

The capacity for perpetual self‐renewal is one of the main characteristics of stem cells. Little is known about the effect of embryonic neural stem cell (NSC)‐secreted factors on auditory cell proliferation in vitro. In the present work, two auditory cell types were cultured in the presence of NSC‐secreted molecules and were evaluated in vitro. Our results demonstrated that both cell viability and cell proliferation were significantly enhanced upon treatment with NSC conditioned medium, which contains significantly elevated levels of leukemia inhibitory factor (LIF) secreted by NSCs. The NSC conditioned medium not only activated the expression of leukemia inhibitory factor receptor in House Ear Institute‐organ of Corti 1 cells but also up‐regulated the LIF downstream signal transducers and activators of transcription (STAT) 1 and STAT3. Blocking either the LIF signaling pathway with neutralizing antibodies or the downstream Janus kinase (JAK)/STAT pathway with JAK2 inhibitor AG490 resulted in a dose‐dependent inhibition of cell proliferation, suggesting that NSC‐secreted molecules promote auditory cell survival via the regulatory LIF/JAK/STAT signaling pathway.

Effect of cooling on electrical field stimulation and norepinephrine-induced contraction in isolated hypertrophic human nasal mucosa.

Background Exposure to cold causes cutaneous vasoconstriction to reduce body heat loss, while the nasal cavity warms up the inspired cold air. This suggests cooling might evoke a different response in nasal mucosa blood vessels than in cutaneous blood vessels. Thus, the aim of this study was to evaluate the effect of cooling (to 24°C) on the vascular response of isolated nasal mucosa. Methods An in vitro isometric contraction of nasal mucosa excised from patients suffered from chronic nasal congestion was continuously recorded. Either electrical field stimulation (EFS) or exogenous norepinephrine (NE) was applied to the turbinate mucosa strip at 37 and 24°C, and the influence of cooling (to 24°C) was evaluated. Results EFS (1, 2, 4, and 8 Hz) produced frequency-dependent contractions at 37 and 24°C. Cooling did not alter the magnitude but significantly prolonged the duration of EFS-induced contraction. Exogenous NE (10-8 to 10-4 M) produced concentration-dependent contractions at 37 and 24°C. Cooling significantly enhanced the contractile responses evoked by NE between 3 × 10-6 and 1 × 10-4 M. Conclusion Cooling (to 24°C) prolonged the EFS-induced and enhanced NE (3 × 10-6 to 1 × 10-4 M)-induced contraction of isolated human nasal mucosa.

Prevalence of the uncinate process, agger nasi cell and their relationship in a Taiwanese population.

OBJECTIVES The uncinate process (UP) and the agger nasi (AN) cell are both important anatomical landmarks in endoscopic sinus surgery. The superior attachment of the UP and the prevalence of the AN cell show great anatomical variability and affect the anatomy of the frontal recess. The aim of this study was to investigate the superior attachment types of the UP, the presence of the AN cell, and the relationship between the two. METHOD Two hundred sixty-four sides of 132 patients with identifiable superior attachments of the UP were selected from our 2007-08 computed tomography (CT) scan records. Exclusion criteria were previous nasal or paranasal sinus surgery, neoplastic disease, and a history of nasal trauma. The superior attachment type of the UP and the prevalence of the AN cell were evaluated. Three case series from the English-language literature were selected for racial comparison. RESULTS Single insertion of the UP into the lamina papyracea was the most common type (70.4%). The other types of UP superior attachment were found to have the following distribution: 10.2% into the middle turbinate; 7.6% into the lamina papyracea and the skull base; 6.1% into the skull base, 4.9% into the lamina papyracea and the middle turbinate; and 0.8% into the middle turbinate and the skull base. The distribution of the UP insertion types with respect to ethnicity was statistically significant (P < 0.01). The AN cell was found in 216 (81.8%) of 264 sides. The AN cell was present bilaterally in 95.3% of the cases (206 sides, 103 patients) and unilaterally in 4.7% (10 sides). The prevalence of the AN cell according to superior attachment of the UP types was not statistically significant (chi(2) = 8.6, p = 0.126). CONCLUSIONS The nasofrontal anatomy did show some variations among different races. The single superior attachment of the UP into the lamina papyracea had the highest prevalence. The AN cell was found to be present in 81.8% of cases. The relationship between the presence of the AN cell and the superior attachment types of the UP was not statistically significant.

High Computed Tomographic Correlations between Carotid Canal Dehiscence and High Jugular Bulb in the Middle Ear

Both carotid canal dehiscence (CCD) and high jugular bulb (HJB) are thought to increase the potential for disastrous consequences during middle ear surgery. Clinical co-presentation of these two great vessel variants has not yet been described. This study aims to determine the relationship between CCD and HJB based on a computed tomographic (CT) temporal bone evaluation. High-resolution CT scans of 408 temporal bones obtained from 208 adults were recruited. Carotid canal integrity, jugular bulb position, petrous apex pneumatization and the minimal thickness of the carotid canal wall (TCW) facing the tympanic cavity were examined and measured for the incidence of CCD and/or HJB. Other variables including gender, age, laterality and the presence of otitis media or mastoiditis were also collected for analysis. CCD was found in 28 ears (6.9%); 19 of these were found to also have HJB (67.9%). The presence of CCD was significantly correlated with HJB presentation. The minimal TCW in HJB ears was significantly thinner than that of normally positioned jugular bulbs. Moreover, after controlling for other candidate variables, the independent factors of age (younger or older than 50 years) and jugular bulb position (high vs. normal) were found to predict the presence of CCD. In conclusion, HJB tends to coexist with a thinner carotid canal wall. This finding emphasizes the need to be watchful for the coexistence of these two great vessel anomalies when surgeons encounter an aged patient presenting either CCD or HJB during middle ear surgery.

Identification of the cold receptor TRPM8 in the nasal mucosa.

Background The transient receptor potential channel melastatin 8 (TRPM8) has been proposed to be a cold receptor. However, its distribution and physiologic role in the nose is not yet fully explored. Objective We investigated the expression of TRPM8 in human nasal mucosa and its function when using the TRPM8 agonist. Methods Immunohistochemistry was used to study TRPM8 receptors in the nasal mucosa from patients with and those without allergic rhinitis (AR). By using isometric contraction studies, we also tested the effectiveness of the TRPM8 agonist menthol on nasal mucosa. Changes in nasal mucosal contractility in response to the application of the adrenergic agent methoxamine were also measured. We explored the effect of menthol on electrical field stimulation (EFS) induced nasal mucosal contractions. Results TRPM8 immunoreactivity was present principally in the nasal cilia, epithelium, and subepithelium around the glands. Except for nerve fibers, no obvious TRPM8-immunoreactive cells were detected in connective tissues. The immunoreactivity revealed no significant difference between patients with AR and those without AR. Adding menthol had a negligible effect on the basal tension of the nasal mucosa, but higher doses of menthol had a significant spasmolytic effect on nasal mucosa precontracted with methoxamine. Menthol inhibited the spike contraction induced by EFS, even at low doses. Conclusions The finding of the TRPM8 immunoreactivity underlines the important physiologic role of the nose in temperature regulation, both in patients with allergy and those without allergy. Isometric contraction studies demonstrate the role of TRPM8 in regulating nasal patency and airway resistance. The antiadrenergic effect of menthol showed an effect apparently opposite that of clinical observations, that we usually feel decongested after menthol inhalation. The underlying mechanisms deserve further investigation, and the TRPM8 antagonists deserve consideration for treatment of rhinitis in a therapeutic trial.

Using image processing technology and mathematical algorithm in the automatic selection of vocal cord opening and closing images from the larynx endoscopy video

The human larynx is an important organ for voice production and respiratory mechanisms. The vocal cord is approximated for voice production and open for breathing. The videolaryngoscope is widely used for vocal cord examination. At present, physicians usually diagnose vocal cord diseases by manually selecting the image of the vocal cord opening to the largest extent (abduction), thus maximally exposing the vocal cord lesion. On the other hand, the severity of diseases such as vocal palsy, atrophic vocal cord is largely dependent on the vocal cord closing to the smallest extent (adduction). Therefore, diseases can be assessed by the image of the vocal cord opening to the largest extent, and the seriousness of breathy voice is closely correlated to the gap between vocal cords when closing to the smallest extent. The aim of the study was to design an automatic vocal cord image selection system to improve the conventional selection process by physicians and enhance diagnosis efficiency. Also, due to the unwanted fuzzy images resulting from examination process caused by human factors as well as the non-vocal cord images, texture analysis is added in this study to measure image entropy to establish a screening and elimination system to effectively enhance the accuracy of selecting the image of the vocal cord closing to the smallest extent.

Augmentation rhinoplasty with bilateral auricular cartilage in Asian patients: how we do it

Dear Editor, Asian aesthetic rhinoplasty differs greatly from Western rhinoplasty because of its unique underlying anatomy. To achieve the ideal aesthetic result, most Asian rhinoplasty is composed of both dorsum augmentation and tip plasty. The ideal material for grafting must have the characteristics of low complication rates and simultaneously high long-term patient satisfaction. Autogenous material, such as auricular, septal and rib cartilage can achieve this goal. In this paper, we limit the discussion to our experiences in dorsal augmentation rhinoplasty with bilateral auricular cartilage in Asian patients.

Low temperature decreased tension in isolated hypertrophic human nasal mucosa

Background The purpose of this study was to evaluate the effect of low temperature on basal tension in isolated hypertrophic human nasal mucosa with or without α1-agonist stimulation. Methods A tissue bath for isolated nasal mucosa was used. Tension in strips of human turbinate mucosa that were untreated and treated with an α1-adrenoreceptor agonist, methoxamine (10 μM), was recorded continuously in a stepwise manner in temperatures that varied from 37 to 10°C. Results The changes of tension in the human nasal mucosa were found to be temperature-dependent in both untreated and treated tissues, with tension decreasing to 48.6% at 10°C in comparison with 100% at 37°C in the untreated group, the presence of methoxamine (10 μM) had minimal effect. Conclusion Low temperature induced a rapid and reproducible relaxation in isolated hypertrophic human nasal mucosa that was not affected by the presence of the α1-agonist methoxamine (10 μM).

Effects of bambuterol and terbutaline on isolated rat’s tracheal smooth muscle

Terbutaline (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent β2-adrenoceptor agonists often used in asthma patients. Terbutaline in the form of inhaled short-acting bronchodilator relieves asthmatic symptoms. However, the effects of bambuterol given intratracheally have rarely been explored. To verify the effect of bambuterol and terbutaline, which act on the tracheal smooth muscle directly in vitro, we used our preparation to test the effects of bambuterol on isolated rat’s tracheal smooth muscle compared with terbutaline. The following assessments of bambuterol and terbutaline were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10−6 M methacholine as a parasympathetic mimetic; (3) effect of the drugs on electrically induced tracheal smooth muscle contractions. The results indicated that adding bambuterol induced a significant further contraction to 10−6 M methacholine-induced contraction when the preparation was increased to 10−4 M. But terbutaline elicited a relaxation response at a dose of 10−6 M or more. Both bambuterol and terbutaline could inhibit electrical field stimulation (EFS) induced spike contraction. Terbutaline had an anti-cholinergic effect that could relieve asthmatic symptoms. But the effect of bambuterol acting on tracheal smooth muscle directly was controversial.