Introduction We have previously demonstrated that Sinupret, an established treatment prescribed widely in Europe for respiratory ailments including rhinosinusitis, promotes transepithelial chloride (Cl−) secretion vitro and vivo. The present study was designed to evaluate other indicators of mucociliary clearance (MCC) ciliary beat frequency (CBF) airway surface liquid (ASL) depth, but also investigate the mechanisms underlie activity this bioflavonoid. Methods Primary murine nasal septal...

Pseudomonas aeruginosa is frequently implicated in difficult-to-treat infectious cases due to its resistance conventional antibiotics and ability form biofilms [1, 2]. To avoid limitations of systemic antibiotic drug delivery, our previous studies explored the feasibility a localized treatment approach using novel ciprofloxacin azithromycin sinus stent (CASS) treat sinusitis [3, 4]. It double-layered, with an inner hydrophilic outer hydrophobic azithromycin. This double-layered coating...

Abstract Objective Cystic fibrosis (CF) is a clinical entity defined by aberrant chloride (Cl − ) ion transport causing downstream effects on mucociliary clearance (MCC) in sinonasal epithelia. Inducible deficiencies transepithelial Cl via CF transmembrane conductance regulator (CFTR) has been theorized to be driving process recalcitrant chronic rhinosinusitis (CRS) patients without CF. We have previously identified that brief exposures bacterial lipopolysaccharide (LPS) mammalian cells...

Objectives/Hypothesis: Sinonasal respiratory epithelial mucociliary clearance is dependent on the transepithelial transport of ions such as Cl−. The objectives present study were to investigate role oxygen restriction in 1) Cl− across primary sinonasal monolayers, 2) expression apical channels cystic fibrosis transmembrane conductance regulator (CFTR) and protein 16A (TMEM16A), 3) pathogenesis chronic rhinosinusitis. Study Design: In vitro investigation. Methods: Murine nasal septal (MNSE),...

Abstract Objectives/Hypothesis: Evidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature to chronic rhinosinusitis. Tobacco‐smoke exposure thought inhibit transepithelial Cl − secretion, determinant of airway surface liquid hydration and MCC. The objective the current study was evaluate effects acrolein (a prominent tobacco smoke toxin) on vectorial transport through apical anion channel cystic fibrosis transmembrane conductance regulator (CFTR) in...

BackgroundChronic rhinosinusitis engenders enormous morbidity in the general population, and is often refractory to medical intervention. Compounds that augment mucociliary clearance airway epithelia represent a novel treatment strategy for diseases of mucus stasis. A dominant fluid electrolyte secretory pathway nasal airways governed by cystic fibrosis transmembrane conductance regulator (CFTR). The objectives present study were test resveratrol, strong potentiator CFTR channel open...

Methods to improve the clinical efficacy of currently available antibiotics against multidrug resistant bacteria in cystic fibrosis (CF) chronic rhinosinusitis (CRS) are greatly needed. Ivacaftor, a transmembrane conductance regulator potentiator, was recently identified as having potentially beneficial off-target effects weak inhibitor bacterial DNA gyrase and topoisomerase IV. The objective current study is evaluate whether ivacaftor enhances antimicrobial activity ciprofloxacin...

Background: Rabbits are useful for preclinical studies of sinusitis because similar physiologic features to humans. The objective this study is develop a rabbit model that permits assessment microanatomy and sampling evaluating shifts in the sinus microbiota during development test how mucociliary clearance (MCC) defect might lead dysbiosis chronic rhinosinusitis (CRS). Methods: Generation CRS was accomplished with an insertion sterile sponge into left middle meatus New Zealand white rabbits...

Abstract Objective/Hypothesis: Therapeutic agents that enhance mucociliary transport (via stimulation of transepithelial Cl − secretion) and inhibit inflammation could provide considerable advantages over conventional treatments for chronic rhinosinusitis (CRS). The objectives the present study were to investigate whether polyphenolic compound resveratrol promotes inhibits KC/IL‐8 secretion in sinonasal epithelium. Study Design: In vitro vivo study. Methods: Transepithelial was investigated...

Pharmacologic agents designed to promote mucociliary clearance (MCC) in chronic rhinosinusitis (CRS) represent a novel therapeutic strategy. The objectives of the present study were investigate whether natural bioflavonoid hesperidin 1) increases transepithelial chloride (Cl(-)) secretion vitro and vivo, 2) enhances ciliary beat frequency (CBF), 3) exerts its mechanistic effects through cAMP/PKA-dependent pathways.In vivo study.Laboratory.Transepithelial Cl(-) transport (Ussing chamber) CBF...

IMPORTANCE Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence congenital mutations CFTR gene.Drug discovery efforts have identified small molecules that activate cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development treatment fibrosis.OBJECTIVE To evaluate properties modulators and their effects on ciliary beat frequency (CBF) human...

Background Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (Cl − ) transport is one such mechanism that contributes this disorder and can be acquired secondary environmental perturbations, as hypoxia at the tissue surface. The objective study was assess technological feasibility novel micro‐optical coherence tomography (μOCT) imaging technique for investigating...

Enhancing chloride (Cl- ) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl- sinonasal cultures vitro and murine epithelium vivo. The objective this study is evaluate whether the improves MCC clinical parameters rabbit model CRS.After development CRS 30 New Zealand white rabbits, animals were randomly assigned receive oral placebo (n = 10), (low dose...

Background Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in sinuses could mitigate side effects improve drug concentrations at infected site. This study was aimed evaluate efficacy of novel ciprofloxacin‐azithromycin sinus stent (CASS) vitro. Methods The CASS created coating ciprofloxacin...

Background Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor absorption, and minimal depletion. The objectives current study were to analyze in vitro release rate vivo drug delivery tolerance pharmacokinetics a ciprofloxacin‐coated sinus stent (CSS). Methods CSS (2 mg) was...

Background We recently developed a novel ciprofloxacin‐coated sinus stent capable of releasing antibiotics over sustained period time. Ivacaftor is cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has synergistic bactericidal activity with ciprofloxacin and also enhances mucociliary clearance. The objective this study was to optimize evaluate the efficacy ciprofloxacin‐ ivacaftor‐releasing biodegradable (CISS) in vitro. Methods A CISS created by coating...

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result defective Cl- transport and cause chronic bacterial infections upper lower airways of (CF) patients. Ivacaftor is a CFTR potentiator that improves CF patients with at least 1 copy G551D mutation. Resveratrol also potent increases determinants mucociliary transport. The objective this study to determine whether resveratrol ivacaftor improve secretion over either agent alone.Fisher rat thyroid cells (FRT)...

Objectives Previously, we developed a novel double‐coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are improve release of CASS assess safety pharmacokinetics in rabbits. Methods Dip coating was used create the with 2 mg 5 azithromycin. A uniformed double assessed scanning electron microscopy (SEM), patterns both drugs lactate dehydrogenase (LDH) assay...

Background The ciprofloxacin‐coated sinus stent (CSS) has unique therapeutic potential to deliver antibiotics the sinuses. objective of this study is evaluate efficacy CSS in eliminating Pseudomonas aeruginosa infection a rabbit model sinusitis. Methods A ciprofloxacin‐eluting was created by coating ciprofloxacin/Eudragit RS100 on biodegradable poly‐D/L‐lactic acid (2 mg). After analyzing in‐vitro inhibition P (PAO‐1 strain) biofilm formation, total 8 stents (4 shams, 4 CSSs) were placed...

Salubrious effects of the green coffee bean are purportedly secondary to high concentrations chlorogenic acid. Chlorogenic acid has a molecular structure similar bioflavonoids that activate transepithelial Cl(-) transport in sinonasal epithelia. In contrast flavonoids, drug is freely soluble water. The objective this study evaluate secretory capability and its potential as therapeutic activator mucus clearance sinus disease.Basic research.Laboratory.Chlorogenic was tested on primary murine...

Background: Chronic rhinosinusitis (CRS) is characterized by complex bacterial infections with persistent inflammation. Based on our rabbit model of sinusitis, blockage sinus ostia generated a shift in microbiota to predominance mucin degrading microbes (MDM) acute inflammation at 2 weeks. This was followed conversion chronic 3 months robust increase pathogenic bacteria (e.g., Pseudomonas). MDMs are known produce acid metabolites [short chain fatty acids (SCFA)] that have the potential...

Lipopolysaccharide (LPS) serves as the interface between gram-negative bacteria (GNB) and innate immune response in respiratory epithelial cells (REC). Herein, we describe a novel biological role of LPS that permits GNB to persist tract through inducing CFTR mucociliary dysfunction. reduced cystic fibrosis transmembrane conductance regulater (CFTR)-mediated short-circuit current mammalian REC Ussing chambers nearly abrogated single channel activity (defined forskolin-activated Cl- currents)...

Background Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin ivacaftor‒releasing biodegradable sinus stent (CISS)―a drug‐delivery system that administers mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time sustained delivery. The objective of this study evaluate efficacy CISS a rabbit model P (PAO1 strain) sinusitis. Methods...

Background The Lactococcus strain of bacteria has been introduced as a probiotic nasal rinse for alleged salubrious effects on the sinonasal bacterial microbiome. However, data regarding interactions with pathogenic within sinuses are lacking. purpose this study is to assess interaction between L. lactis and patient‐derived Pseudomonas aeruginosa , an opportunistic pathogen in recalcitrant chronic rhinosinusitis (CRS). Methods Commercially available suspension containing W136 was grown...

Background Decreased cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride (Cl) secretion across mucosal surfaces contributes to the development of airway disease by depleting surface liquid, increasing mucus viscosity and adhesion, consequently hindering mucociliary clearance. We serendipitously discovered during testing drugs solubilized in low concentrations ethanol (0.25%, 43 mM) that control vehicle produced robust activation CFTR-mediated Cl− transport. The...