Effects of Ephedrine on Human Nasal Ciliary Beat Frequency

Zhang, Luo; Han, Demin; Song, Xiaohong; Wang, Hong; Wang, Kuiji; Liu, Zhongyan

doi:10.1159/000114531

Cited by 14 publications

(13 citation statements)

References 31 publications

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“…Unless stated otherwise, 40 and 600 μl medium with or without drugs was kept in the apical and basolateral side of transwell inserts (3470; Corning), respectively. All the experiments were performed at 26°C (18,19) to ensure a steady baseline frequency during the experiment. To keep the air pressure delivered to the cell surface the same in all experiments, the catheter was connected via a rigid plastic boom to a micromanipulator, allowing for accurate, precise, and reproducible placement 6 mm above the apical fluid and 1 mm from the wall of the transwell, thus leaving the center of the transwell unobstructed for observation and video recording.…”

Section: Methodsmentioning

confidence: 99%

Molecular modulation of airway epithelial ciliary response to sneezing

et al. 2012

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Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26°C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by ≥150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease.

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Section: Methodsmentioning

confidence: 99%

Molecular modulation of airway epithelial ciliary response to sneezing

et al. 2012

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“…The apical side of the transwell was copiously washed with PBS to remove any mucus clumps and then 20 µL of PBS was added to the surface. Cultures were then allowed to equilibrate for 15 minutes to the ambient 26°C temperature to ensure a steady baseline CBF . Baseline CBF was recorded for 1 minute and percentage change from baseline over 15 minutes after PBS or ketotifen addition was determined.…”

Section: Methodsmentioning

confidence: 99%

“…Cultures were then allowed to equilibrate for 15 minutes to the ambient 26°C temperature to ensure a steady baseline CBF. 34,35 Baseline CBF was recorded for 1 minute and percentage change from baseline over 15 minutes after PBS or ketotifen addition was determined.…”

Section: Pharmacologic Manipulationmentioning

confidence: 99%

In vitro safety of ketotifen as a topical nasal rinse

Triantafillou

Maina

Patel

et al. 2020

Int Forum Allergy Rhinol

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Background Ketotifen is a second‐generation noncompetitive H1‐antihistamine and mast‐cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast‐cell, and other allergic‐type disorders. However, it has never been studied in aspirin‐exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis. Methods Human sinonasal epithelial cells were grown at an air‐liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long‐term cellular toxicity. Results Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures. Conclusion Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long‐term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD.

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“…The apical side of the transwell was copiously washed with PBS to remove any mucus clumps and then 30 μL of PBS was added to the surface. Cultures were then allowed to equilibrate for 15 minutes to the ambient 26°C temperature to ensure a steady baseline CBF . Three conditions were tested: control (PBS), OM‐85 BV, and OM‐85 BV + L‐N G ‐nitroarginine methyl ester (L‐NAME) (Sigma‐Aldrich, St. Louis, MO) a specific inhibitor of nitric oxide synthase (NOS).…”

Section: Methodsmentioning

confidence: 99%

Broncho‐Vaxom® (OM‐85 BV) soluble components stimulate sinonasal innate immunity

Triantafillou

Workman

Patel

et al. 2019

Int Forum Allergy Rhinol

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Background: Broncho-Vaxom R (OM-85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have shown that use of OM-85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM-85 BV on respiratory mucosal innate immunity are unknown. Methods:Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM-85 BV was measured in vitro. Pharmacologic inhibitors of bi er taste receptor (T2R) signaling were used to determine if this pathway was taste-receptor-mediated. Results:Apical application of OM-85 BV resulted in an NOmediated increase in CBF (p < 0.05) and increased NO production (p < 0.0001) when compared to saline-stimulated control cultures. ALI pretreatment with taste receptor pathway inhibitors blocked OM-85 BV-induced increases in NO.Conclusion: OM-85 BV has ciliostimulatory and immunogenic properties that may be partially responsible for its observed efficacy as a respiratory therapeutic. These responses were NO-dependent and consistent with T2R activation. Further work is necessary to elucidate specific component-receptor signaling relationships. C 2019 ARS-AAOA, LLC.

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Effects of Ephedrine on Human Nasal Ciliary Beat Frequency

Cited by 14 publications

References 31 publications

Molecular modulation of airway epithelial ciliary response to sneezing

Molecular modulation of airway epithelial ciliary response to sneezing

In vitro safety of ketotifen as a topical nasal rinse

Broncho‐Vaxom® (OM‐85 BV) soluble components stimulate sinonasal innate immunity

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