Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

Efficacy of vardenafil in human nasal mucosa.

OBJECTIVE: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. It is applied to treatment of erectile dysfunction. PDE5 inhibitors dilate the penile blood vessels and cause prolonged erections. However, the effects of Levitra on human nasal mucosa are not yet fully explored. MATERIALS AND METHODS: We examined the effectiveness of Levitra on human nasal mucosa directly in vitro by testing: 1) effect on human nasal mucosa resting tension; 2) effect on contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) effect of the drugs on electrically induced human nasal mucosa contractions. RESULTS: The results showed that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Levitra at doses of 10-4 M elicited a significant relaxation response to 10-6 M methoxamine-induced mucosa strip contraction. Levitra could not inhibit electrical field stimulation-induced spike contraction and had a minimal effect on the basal tension of nasal mucosa as the concentration increased. CONCLUSION: This study indicated that high concentrations of Levitra had a significant spasmolytic effect by antagonizing α-adrenoceptors. Moreover, nasal obstruction might not be relieved in patients suffering from erectile dysfunction and stuffy noses who were concomitant using α-adrenergic agonist and Levitra.

Effects of montelukast on human nasal mucosa.

OBJECTIVE: Montelukast is a selective and orally active leukotriene D4 receptor antagonist often used in treating asthma and allergic rhinitis. Montelukast nasal spray was developed to avoid systemic adverse effects of the drug in vitro. However, the effects of montelukast on human nasal mucosa are not yet fully explored and potential nasal vascular side effects of the drug merit further exploration. First, the effects of montelukast on vasocontractile responses generated by smooth muscles in the vascular structures of human nasal mucosa were investigated directly in vitro. METHODS: This study examined the effects of montelukast on human nasal mucosa in terms of mucosa resting tension, vasoconstriction caused by 10- 6 M methoxamine as a sympathetic mimetic, and electrically induced vasoconstrictions. RESULTS: The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to vasocontract in a dose-dependent manner. Addition of montelukast at doses of 10- 5 M or above elicited a significant vasodilation response to 10- 6 M methoxamine-induced vasoconstriction. Montelukast could not inhibit electrical field stimulation-induced spike vasoconstriction. Moreover, increase in concentration of montelukast had minimal effect on basal tension of nasal mucosa. CONCLUSIONS: The study indicated significant vasodilation on human nasal mucosa under high concentrations of montelukast with a probable α-adrenoceptor antagonism. Hence, the nasal activity of α-adrenergic agonist nasal spray for nasal obstruction may be reduced in those using concomitant (oral or local spray) montelukast.

Nasal septal abscess: a 10-year retrospective study.

OBJECTIVE: Nasal septal abscess is an uncommon condition but it can cause potentially life-threatening intracranial complications and cosmetic nasal deformity. METHODS: We analyzed ten years of cases to determine the optimal diagnostic and therapeutic modalities. A retrospective review of case notes from Tri-Service General Hospital archives was performed. Records of six patients diagnosed with nasal septal abscess, who were treated from September 2007 to August 2017 were retrospectively reviewed. Patients' clinical symptoms, etiology, diagnostic methods, bacteriology, antibiotic and surgical treatment were recorded and analyzed. RESULTS: Out of six patients diagnosed with nasal septal abscess, three were male and three were female. Ages ranged from 19 to 75 years (mean 51 years). The most common symptoms at presentation were nasal pain and nasal obstruction. Typical etiologies were trauma or acute sinusitis, but uncontrolled diabetes mellitus was also an important etiology. In the series of six patients, four of them had positive findings of abscess and in drainage, had the following bacterial cultures: Staphylococcus aureus (two cases), methicillin-resistant S. aureus (one case), and Klebsiella pneumoniae (one case). In addition to antibiotic treatment, all patients underwent surgical drainage and had complete resolution of disease without intracranial complications during at least 1 year of follow-up. However, two out of the six patients developed saddle nose deformity. CONCLUSIONS: This study highlights that: 1. In view of the rapidly increasing number of diabetes mellitus cases, uncontrolled diabetes mellitus is an important etiology of nasal septal abscess. 2. Although S. aureus is the most common pathogen, we must pay attention to methicillin-resistant S. aureus (MRSA) to prevent severe complications and patients who are at increased risk for MRSA colonization should be administrated antibiotics against MRSA initially. 3. Nasal septal abscess should be managed with parenteral broad spectrum antibiotics, appropriate drainage and immediate reconstruction of the destructed septal cartilage with autologous cartilage graft, to prevent serious intracranial complications and cosmetic nasal deformity.

Enhanced basal tension in isolated rat tracheal smooth muscle stimulated by electric field stimulation under low temperature.

Exposure to cold causes cutaneous vasoconstriction to reduce body heat loss, while the airway warms up the inspired cold air, thus suggesting that cooling might evoke a response in tracheal smooth muscle different from that in cutaneous blood vessels. The aim of this study was to evaluate the effect of temperature on isolated rat trachea, with or without electric field stimulation (EFS). Tissue bath for isolated trachea was used. An in vitro isometric contraction of trachea from healthy male Sprague-Dawley rat (body weight: ≥ 200 g) was continuously recorded. Tension in strips of rat trachea that were untreated and treated with EFS, was continuously recorded in stepwise manner at temperatures varying from 37 °C to 7 °C or from 7 °C to 37 °C. Results indicated that descent and re-ascent of temperature produced temperature-dependent tension changes. Basal tension of the trachea decreased when temperature was reduced if EFS was not applied. EFS-induced spike contraction decreased when temperature was reduced, while basal tension increased at the same time. We concluded that low temperature induced rapid and reproducible contraction in isolated rat tracheal strip only if EFS was applied. Increasing temperature reduced basal tension and enhanced EFS-induced spike contraction of the trachea at the same time.

Chlorpheniramine attenuates histamine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation.

Background: Aquaporin 5 (AQP5) is most likely the primary water channel in the human nasal mucosa and acts as a key tight junction protein. The signaling cascades responsible for AQP5 regulation are still works in progress. Objective: This study sought to determine the effects of histamine and chlorpheniramine on AQP5 expression in human nasal epithelial cells (HNEpC) and to detect the signaling cascades responsible for these effects. Methods: HNEpC were cultured with four concentrations of histamine or chlorpheniramine in vitro. The sub-cellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of histamine and chlorpheniramine on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), the AQP5 and the NF-κB protein were examined using Western blotting. Results: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without significant difference. Histamine inhibits the expression of AQP5 and p-CREB in HNEpC, while chlorpheniramine dose-dependently increases these protein levels with statistical significance. HNEpC treated with histamine and chlorpheniramine in turn showed the same trends as those intervened separately with these two drugs. Moreover, chlorpheniramine had the ability to reverse the inhibitory effect of histamine. Western blotting analysis revealed that after incubation with 10-4 M histamine, NF-κB protein was significantly heightened by 165% compared with the untreated control group. Again, such increase can be significantly reversed after chlorpheniramine treatment. Conclusions: The current study demonstrated that histamine inhibits CREB phosphorylation in HNEpC, which results in decreased AQP5 expression via activation of NF-κB pathway. Chlorpheniramine attenuates the inhibitory effect of histamine in p-CREB/AQP5 expression via suppression of NF-κB signal cascades. This observation could provide additional insight into the anti-inflammatory effects of H1-antihistamines that contribute to maintain airway surface liquid and mucosal defense.

Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol 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 drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Steroids and antihistamines synergize to inhibit rat's airway smooth muscle contractility.

Both glucocorticoids and H1-antihistamines were widely used on patients with allergic rhinitis (AR) and obstructive airway diseases. However, their direct effects on airway smooth muscle were not fully explored. In this study, we tested the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of the drug were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine; (3) effect of the drug on electrical field stimulation (EFS) induced tracheal smooth muscle contractions. The result revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a little relaxation response on tracheal tension after methacholine treatment. The tension was 90.5 ± 7.5 and 99.5 ± 0.8 % at 10(-4) M for Xyzal and 10(-5) M for Kidsolone, respectively. However, a dramatically spasmolytic effect was observed after co-administration of Kidsolone and Xyzal and the tension dropped to 67.5 ± 13.6 %, with statistical significance (p < 0.05). As for EFS-induced contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with increasing basal tension. In conclusion, using glucocorticoids alone had no spasmolytic effect but they can be synergized with antihistamines to dramatically relax the trachea smooth muscle within minutes. Therefore, for AR patients with acute asthma attack, combined use of those two drugs is recommended.

Effects of sumatriptan nasal spray (Imigran) on isolated rat's tracheal smooth muscle.

Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran given intratracheally have rarely been well explored. We aimed to verify the effect of Imigran, which acts on the tracheal smooth muscle directly in vitro. We examined the effectiveness of Imigran on isolated rat tracheal smooth muscle by testing: (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 the addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. The addition of Imigran at doses of 10(-5) M or above elicited a significant relaxation response to 10(-6) M methacholine-induced contraction. Imigran could inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of trachea as the concentration increased. The study indicated high concentrations of Imigran could cause bronchodilation to reduce asthma attacks not only by blocking parasympathetic tone, but also by directly antagonizing the effect of cholinergic receptors.

Effects of levobupivacaine on isolated rat tracheal smooth muscle.

Levobupivacaine has been developed as a safer alternative to bupivacaine because of its reduced systemic toxicity. However, the effect of directly delivering levobupivacaine into tracheal smooth muscle has not been adequately explored. We performed this study to determine the in vitro effects of levobupivacaine on isolated rat tracheal smooth muscle. A portion of rat trachea 5 mm in length was mounted in 30 ml of Krebs solution in a muscle bath at 37 °C. The following effects of levobupivacaine were assessed: (1) the effect on tracheal smooth muscle resting tension (n = 6), (2) the effect on contraction caused by 10(-6) M methacholine (n = 6) and (3) the effect on electrically induced tracheal smooth muscle contractions (n = 6). Levobupivacaine caused dose-dependent relaxation in the trachealis muscle precontracted with 10(-6) M methacholine. Contraction inhibition was statistically significant when 10(-5) and 10(-4) M levobupivacaine were applied, compared with the contraction inhibition that occurred in the control groups (p < 0.01). A high dose of levobupivacaine also decreased the spike contraction induced by electrical field stimulation. This study indicated that high concentrations of levobupivacaine might antagonize the cholinergic receptors and inhibit parasympathetic function of the trachea.

The effect of temperature on basal tension and thyroarytenoid muscle contraction in an isolated rat glottis model.

The pitch of voice is closely related to the vocal fold tension, which is the end result of coordinated movement of the intralaryngeal muscles, and especially the thyroarytenoid muscle. It is known that vocal quality may be affected by surrounding temperature; however, the effect of temperature on vocal fold tension is mostly unknown. Thus, the aim of this study was to evaluate the effect of temperature on isolated rat glottis and thyroarytenoid muscle contraction induced by electrical field stimulation. In vitro isometric tension of the glottis ring from 30 Sprague-Dawley rats was continuously recorded by the tissue bath method. Electrical field stimulation was applied to the glottis ring with two wire electrodes placed parallel to the glottis and connected to a direct-current stimulator. The tension changes of the rat glottis rings that were either untreated or treated with electrical field stimulation were recorded continuously at temperatures from 37 to 7 °C or from 7 to 37 °C. Warming from 7 to 37 °C increased the basal tension of the glottis rings and decreased the electrical field stimulation-induced glottis ring contraction, which was chiefly due to thyroarytenoid muscle contraction. In comparison, cooling from 37 to 7 °C decreased the basal tension and enhanced glottis ring contraction by electrical field stimulation. We concluded that warming increased the basal tension of the glottis in vitro and decreased the amplitude of electrical field stimulation-induced thyroarytenoid muscle contraction. Thus, vocal pitch and the fine tuning of vocal fold tension might be affected by temperature in vivo.

Twisted nose: a new simple classification and surgical algorithm in Asians.

The purpose of this study was to present our experiences with correction of twisted nose in Asian patients using a new and simple classification and a surgical algorithm. A classification and standard surgical algorithm was followed to determine treatment strategies for 384 patients with twisted nose between June 2001 and July 2009. A retrospective chart review from the Tri-Service General Hospital archives was performed to collect patients' data and surgical details. A follow-up self-evaluation survey regarding satisfaction with nasal function and esthetics was distributed to all participants. Preoperative and postoperative standardized photography of the face were evaluated to judge objectively the esthetic outcomes of the surgery. There were 147, 131, and 106 patients in Type I, Type II, and Type III patients, respectively. The percentages of functionally satisfied and very satisfied patients were 95.2, 93.9, and 93.4% in Type I, Type II, and Type III groups, respectively. The percentages of esthetically satisfied or very satisfied patients were 89.1, 88.5, and 87.7% in Type I, Type II, and Type III groups, respectively. There were only 2 patients with type III deviation with residual deviation of dorsum objectively who were satisfied with the results after undergoing a revision rhinoplasty. Aside from residual deviation, the postoperative periods were uneventful and without major complications. We propose a new and simple classification and surgical algorithm to optimally correct twisted nose deformities for Asian patients. The classification and surgical algorithm, which is simple and reproducible especially for beginner, guides surgical decisions that yield consistently satisfactory functional and esthetic results.

Anti-cholinergic effect of singulair on isolated rat's tracheal smooth muscle.

Singulair (Montelukast) is a potent and selective leukotriene D(4) receptor antagonist, often used in treating inflammatory conditions of the respiratory system such as allergic rhinitis and asthma. However, the effects of singulair given intratracheally have rarely been well explored. To verify the effect of singulair, which acts on the tracheal smooth muscle directly in vitro. We used our preparation to test the effects of singulair on isolated rat's tracheal smooth muscle. The following assessments of singulair were performed: (1) effect on the tracheal smooth muscle resting tension, (2) effect on contraction caused by 10(-6) M methacholine as a parasympathetic mimetic, and (3) effect of the drugs on electrically induced tracheal smooth muscle contractions. The results indicated that the addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of singulair at doses of 10(-5) M or above elicited a significant relaxation response to 10(-6) M methacholine-induced contraction. Singulair could not inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of trachea as the concentration increased. This study showed that the high concentrations of singulair also had an anti-cholinergic effect for relieving symptoms of asthma.

Head and neck cancers manifested as deep neck infection.

The incidence of head and neck cancers in patients with an initial presentation of deep neck infection is unclear and may be underestimated. Thus, the aim of this study was to assess the incidence of head and neck cancers initially manifested as deep neck infection. Also, the possible risk factors and pathophysiology are discussed. This study was a retrospective medical chart review in a tertiary referral center. A total of 81 consecutive patients admitted with a diagnosis of deep neck infection over a 46-month period were analyzed. The demographic data, physical examinations, laboratory findings, radiographic studies, and pathology report were analyzed. Among the 81 deep neck infection patients, head and neck cancers were histologically demonstrated in four patients (4.9%) with the initial symptom of a painful neck mass. The incidence of head and neck cancer initially manifested as deep neck infection was found to increase in patients aged over 40 years (6.7%; 3/45 vs. 2.8%; 1/36). A detailed history of all patients with deep neck infection should be taken. Furthermore, endoscopic examination, thyroid examination and routine pathological examination should be performed, especially in those aged over 40. Also, careful explanation to the patient and his/her family about the possibility of underlying head and neck cancer (incidence 1-5%) may be needed. If the neck swelling diminishes, but does not disappear completely after full course of antibiotics, repeated fine needle aspiration, endoscopy, or image study should be considered.

Using dynamic analysis of Laser-Doppler blood flowmetry to measure nasal mucosa bloody flow in postural changes.

BACKGROUND: The regulation of nasal mucosa blood flow (NMBF) is affected by multiple factors, such as the autonomic nervous system, medications, temperature, humidity, endocrine, even emotional stress and vision. The effects of postural changes on NMBF have been described in numerous studies. However, the results are far from consistent due to different experimental designs. OBJECTIVE: Dynamic analysis of Laser-Doppler blood flowmetry (LDBF) is employed to recognize the effect of postural changes on NMBF. METHODS: NMBF was continuously measured by LDBF in 14 participants with changing postures (sitting and supine). NMBF was measured in Blood Perfusion Unit (BPU), equivalent to the number of red blood cells multiplied by their mean velocity in a measured volume. RESULTS: NMBF increases significantly in a supine posture compared with that in a sitting posture. CONCLUSION: Our study demonstrates that NMBF is significantly influenced after initial postural change, suggesting that changes in posture may be regarded as an important factor regulating NMBF.

Causes of Vocal Fold Paralysis.

BACKGROUND: Vocal fold paralysis (VFP) can result from a variety of diseases or surgeries and has various causes. This study determined concurrent etiologies in patients who were treated in a teaching hospital (tertiary medical center). METHODS: A retrospective review of medical records of patients with VFP from September 2010 to December 2019 was performed to determine the etiology. Patients with laryngeal/hypopharyngeal malignancies, those with incomplete examination and follow-up data were excluded from the study. During the follow-ups, cases involving recovery were also excluded. RESULTS: One hundred and ninety-four patients with a determined etiology were included: 113 males and 81 females. Unilateral VFP was present in 178 patients, and 16 presented with bilateral VFP. The causes of unilateral VFP were surgical for 61.3%, neoplastic for 17.5%, idiopathic for 10.3%, traumatic for 1.5%, central for 4.7%, cardiovascular for 2%, radiation-induced for 1.5%, and inflammatory for 1%. Thyroidectomy was the most common surgery for unilateral VFP and was the cause for 54 patients. Lung cancer was responsible for 15 cases and was the most common neoplastic etiology of unilateral VFP. For those who presented with bilateral VFP, surgery was the most common cause and accounted for 56.3% of the incidences. In terms of gender, surgery was the most common cause for both sexes, accounting for 62 of 113 male patients and 57 of 81 female patients. Four cases recovered during the follow-ups and these were excluded. CONCLUSION: Surgery and in particular, thyroidectomy, was the most common cause of VFP for these series. Central nervous system disorders were the cause of VFP (4.5%). Central nervous system disorders, especially cerebrovascular accidents that induced VFP, could not be neglected. Radiation-induced cranial nerve paralysis in the head and neck cancer was possible causes. The percentage for the causes of unilateral VFP, surgery increased and the percentage for neoplasm decreased for Taiwan.

Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke.

Murine olfactory ensheathing cells (OECs) promote central nervous system axonal regeneration in models of spinal cord injury. We investigated whether OECs could induce a neuroplastic effect to improve the neurological dysfunction caused by hypoxic/ischemic stress. In this study, human OECs/olfactory nerve fibroblasts (hOECs/ONFs) specifically secreted trophic factors including stromal cell-derived factor-1alpha (SDF-1alpha). Rats with intracerebral hOEC/ONF implantation showed more improvement on behavioral measures of neurological deficit following stroke than control rats. [18F]fluoro-2-deoxyglucose PET (FDG-PET) showed increased glucose metabolic activity in the hOEC/ONF-treated group compared with controls. In mice, transplanted hOECs/ONFs and endogenous homing stem cells including intrinsic neural progenitor cells and bone marrow stem cells colocalized with specific neural and vascular markers, indicating stem cell fusion. Both hOECs/ONFs and endogenous homing stem cells enhanced neuroplasticity in the rat and mouse ischemic brain. Upregulation of SDF-1alpha and CXCR4 in hOECs/ONFs promoted neurite outgrowth of cocultured primary cortical neurons under oxygen glucose deprivation conditions and in stroke animals through upregulation of cellular prion protein (PrP C) expression. Therefore, the upregulation of SDF-1alpha and the enhancement of CXCR4 and PrP C interaction induced by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxia and ischemia.

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.

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.