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.

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.

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.

Image Quality and Performance Benchmarks in Vehicle and Hospital Mammography.

BACKGROUND: Whether the quality and clinical performance of mammograms obtained in vehicles and those obtained in fixed facilities are equal remains unknown. We compared the characteristics of examinees screened in hospital and vehicle settings. PATIENTS AND METHODS: Data from women who had undergone mammography at Shuang Ho Hospital from January 1, 2013, to December 31, 2016, were obtained from the Women's Breast Screening Database and used for analysis. The records revealed that 43,807 and 11,955 women had undergone mammography in vehicle and hospital settings, respectively. The performance benchmarks, including recall rate, cancer detection rate, and positive predictive value, in the 2 settings were compared. In addition, the image quality was compared by reviewing 110 records from each setting. RESULTS: The hospital mammograms had greater subtotal mean scores (189.2 ± 5.9) compared with the vehicle mammograms (185.5 ± 7.7; P < .0001) in the mediolateral oblique view. Mobile mammography contributed to a lower odds ratio of classification in the Breast Imaging Reporting and Data System categories of 0, 4, and 5. In general, all performance benchmarks, including the cancer detection rate and positive predictive value of mobile and hospital mammography, were satisfactory. However, the recall rate with the hospital mammography service was slightly greater than the acceptable benchmark. CONCLUSION: Mobile mammography services should be continued with improvements in image quality. The reduction in the number of patients with a category of 0 in the classification system in both mammography service settings and the enhancement of data linking to previous mammograms warrants additional attention.

Ovatodiolide suppresses inflammatory response in BEAS-2B cells by regulating the CREB/AQP5 pathway, and sensitizes nasopharyngeal carcinoma cells to radiation therapy.

Due to the radiosensitivity of the airway epithelium, radiation-induced sinusitis or bronchitis is not uncommon, and makes mitigation of resulting inflammatory airway diseases a principal goal of many investigations. This study examined whether Ovatodiolide (Ova) sensitizes the human metastatic nasopharyngeal cancer (NPC) cell line, NPC-BM2, to irradiation using viability, clonogenicity and Western blot assays. Concurrently, we used varying concentrations of histamine and/or Ova to determine the anti-inflammatory potential of Ovatodiolide on normal bronchus epithelial BEAS-2B cells, as well as on the subcellular distribution of Aquaporin 5 (AQP5) and expression levels of p-CREB, AQP5, p38 MAPK, NF-κB, PI3K, Akt and ERK proteins. We demonstrated that Ova in synergism with irradiation inhibited NPC-BM2 cell viability and suppressed their clonogenicity. Immunofluorescence analysis revealed low-dose (≤ 2.5 µM) Ova reversed histamine-induced suppression of AQP5 expression, and abrogated histamine-enhanced NF-κB nuclear translocation, indicating Ova modulates the p38 MAPK/NF-κB signaling pathway and elicits p-CREB/AQP5-mediated antihistamine effects. Similarly, Ova deregulates the PI3K/Akt/ERK signaling in BEAS-2B cells, suggesting its cytoprotective potential. In conclusion, this study highlights the radio-sensitizing anticancer efficacy of Ova in human metastatic NPC cells, as well as its putative cytoprotective role in normal bronchial cells, for airway surface liquid maintenance and homeostasis during or after radiotherapy.

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.

Vardenafil inhibiting parasympathetic function of tracheal smooth muscle.

BACKGROUND: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. Nowadays, it is applied to treatment of erectile dysfunction. PDE5 inhibitors are employed to induce dilatation of the vascular smooth muscle. The effect of Levitra on impotency is well known; however, its effect on the tracheal smooth muscle has rarely been explored. When administered for sexual symptoms via oral intake or inhalation, Levitra might affect the trachea. METHODS: This study assessed the effects of Levitra on isolated rat tracheal smooth muscle by examining its effect on resting tension of tracheal smooth muscle, contraction caused by 10-6 M methacholine as a parasympathetic mimetic, and electrically induced tracheal smooth muscle contractions. RESULTS: The results showed that adding methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of Levitra at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Levitra could inhibit electrical field stimulation-induced spike contraction. It alone had minimal effect on the basal tension of the trachea as the concentration increased. CONCLUSION: High concentrations of Levitra could inhibit parasympathetic function of the trachea. Levitra when administered via oral intake might reduce asthma attacks in impotent patients because it might inhibit parasympathetic function and reduce methacholine-induced contraction of the tracheal smooth muscle.

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

BACKGROUND: Cholinergic stimulation plays a major role in inflammatory airway diseases. However, its role in airway surface liquid homeostasis and aquaporin 5 (AQP5) regulation remains unclear. In this study we sought to determine the effects of methacholine and dexamethasone on AQP5 expression in human nasal epithelial cells (HNEpC). METHODS: HNEpC were cultured with methacholine or dexamethasone at 4 concentrations in vitro. The subcellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of methacholine and dexamethasone on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), AQP5, and nuclear factor-kappaB (NF-κB) were examined using Western blotting. RESULTS: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without a statistically significant difference. Methacholine inhibited expression of AQP5 and p-CREB in HNEpC, whereas dexamethasone increased these protein levels dose-dependently in a statistically significant manner. In turn, HNEpC treated with methacholine and dexamethasone showed the same trends as those intervened separately with these 2 drugs. Moreover, dexamethasone had the ability to reverse the inhibitory effect of methacholine. Western blotting revealed that, after incubation with 10-4 mol/L methacholine, NF-κB increased significantly, by 186.67%, compared with the untreated control group. Again, such an increase could be significantly reversed after dexamethasone treatment. CONCLUSION: NF-κB activation is important for inhibition of p-CREB/AQP5 expression after methacholine intervention, and dexamethasone adjusts it to the opposite side. This observation could provide additional insight into the anti-inflammatory effects of glucocorticoids that contribute to maintaining airway surface liquid and mucosal defense.

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.

The identification of the TRPM8 channel on primary culture of human nasal epithelial cells and its response to cooling.

BACKGROUND: It has been proposed that the transient receptor potential (TRP) channel Melastatin 8 (TRPM8) is a cold-sensing TRP channel. However, its presence and its role in the nasal cavity have not yet been fully studied. METHODS: Immunohistology was used to study TRPM8 receptors in both the nasal mucosa tissue and the primary cultures of human nasal cells. Cells from primary cultures were immunostained with antibodies to TRPM8, mucin, cytokeratin (CK)-14, CK-18, and vimentin. Western blotting and real-time polymerase chain reaction (PCR) were used to determine the physiological role of TRPM8 in mucus production in the nasal cavity, with and without its agonist and antagonist. RESULTS: The TRPM8 is clearly present in the epithelium, mucous glands, and vessels. No obvious TRPM8-immunoreactive cells were detected in the connective tissue. Immunostaining of cytospin preparations showed that epithelial cells test positive for CK-14, CK-18, TRPM8, and mucin 5AC (MUC5AC). Fibroblastic cells are stained negative for TRPM8. Secreted mucins in the cultured supernatant are detected after exposure to menthol and moderate cooling to 24°C. Both induce a statistically significant increase in the level of MUC5AC mRNA and mucin production. BCTC, a TRPM8 antagonist, has a statistically significant inhibitory effect on MUC5AC mRNA expression and MUC5AC protein production that is induced by menthol and moderate cooling to 24°C. CONCLUSIONS: The study demonstrates that TRPM8 is present in the nasal epithelium. When it is activated by moderate cooling to 24°C or menthol, TRPM8 induces the secretion of mucin. This study shows that TRPM8 channels are important regulators of mucin production. Therefore, TRPM8 antagonists could be used to treat refractory rhinitis.

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.

Cardiovocal Syndrome Secondary to an Aortic Aneurysm.

We reported that a 68-year-old man presented to the ENT outpatient department complaining of hoarseness for more than 10 months. Clinical exam identified left vocal palsy in the paramedian position and atrophic vocal folds were noted. Chest radiography revealed a large bulging contour overlying aorta and left hilar shadow. Aortic aneurysm was proved by CT scanning. Contrast-enhanced chest computed tomography for further evaluation showed a broad-based aortic aneurysm at proximal descending aorta, projecting anterolaterally. Cardiovocal syndrome was proved. The syndrome is a rare clinical presentation. While a patient with unilateral vocal palsy is encountered, one might keep in mind the possibility of cardiovocal syndrome especially in an adult who had a cardiovascular disease.

A useful technique for adjusting nasal tip projection in Asian rhinoplasty: Trapezoidal caudal extension cartilage grafting.

The purpose of this article is to present our experience with Asian patients in (1) using a trapezoidal caudal extension cartilage graft to adjust the tip projection in tip refinement for augmentation rhinoplasty, especially for the correction of short nose, and (2) avoiding complications of augmentation rhinoplasty with alloplastic implants. We conducted a retrospective chart review of 358 rhinoplasties that were performed by the corresponding author from January 2004 through July 2009. Patients were included in this study if they had undergone open rhinoplasty with a trapezoidal caudal extension cartilage graft as the only tip-modifying procedure. Patients in whom any additional grafting was performed that might have altered the nasal tip position were excluded. The surgical results were analyzed in terms of the degree of satisfaction judged separately by investigators and by patients. A total of 84 patients-46 males and 38 females, all Asians, aged 13 to 61 years (mean: 29.3)-met our eligibility criteria. Postoperative follow-up for 24 months was achieved in 62 patients. At the 24-month follow-up, the surgeons judged the results to be good or very good in 57 of the 62 patients (91.9%); at the same time, 56 patients (90.3%) said they were satisfied or very satisfied with their aesthetic outcome. Good nasal tip projection, a natural columellar appearance, and improvement in the nasolabial angle were achieved for most patients. Two patients required revision rhinoplasty to correct an insufficient augmentation and migration of the onlay graft. No severe complications were observed during the 2-year follow-up. We have found that trapezoidal caudal extension cartilage grafting in nasal tip refinement is an easy technique to learn and execute, its results are predictable, and it has been associated with no major complications. We recommend trapezoidal caudal extension cartilage grafting for Asian patients as a good and reliable alternative for managing tip projection and support.

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.

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.

Benzydamine oral spray inhibiting parasympathetic function of tracheal smooth muscle.

OBJECTIVES: Benzydamine is a nonsteroidal anti-inflammatory agents agent with anti-inflammatory and local anesthesia properties that is available in the entire world as an oral spray for oral mucositis patients who are suffering from radiation effects. The effect of benzydamine on oral mucositis in vivo is well known; however, the effect of the drug on tracheal smooth muscle has rarely been explored. During administration of the benzydamine for oral symptoms, it might affect the trachea via oral intake or inhalation. METHODS: We examined the effectiveness of benzydamine on isolated rat tracheal smooth muscle. The following assessments of benzydamine were performed: effect on tracheal smooth muscle resting tension; effect on contraction caused by 10(-6)M methacholine as a parasympathetic mimetic; and effect of the drug on electrically induced tracheal smooth muscle contractions. RESULTS: Addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of benzydamine at doses of 10(-5)M or above elicited a significant relaxation response to 10(-6)M methacholine-induced contraction. Benzydamine could inhibit electrical field stimulation-induced spike contraction. It alone had a minimal effect on the basal tension of trachea as the concentration increased. CONCLUSION: This study indicated that high concentrations of benzydamine might actually inhibit parasympathetic function of the trachea. Benzydamine might reduce asthma attacks in oral mucositis patients because it could inhibit parasympathetic function and reduce methacholine-induced contraction of tracheal smooth muscle.