RESUMEN
BACKGROUND: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. METHODS: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (µOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. RESULTS: RGAE (at 30µg/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = µA/cm2)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 µm vs control, 3.9+/-0.09 µm; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. CONCLUSION: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.
RESUMEN
BACKGROUND: The ciprofloxacin-coated sinus stent (CSS) has unique therapeutic potential to deliver antibiotics to the sinuses. The objective of this study is to evaluate the efficacy of the CSS stent in eliminating Pseudomonas aeruginosa infection in a rabbit model of sinusitis. METHODS: A ciprofloxacin-eluting sinus stent was created by coating ciprofloxacin/Eudragit RS100 on biodegradable poly-D/L-lactic acid (2 mg). After analyzing in-vitro inhibition of P aeruginosa (PAO-1 strain) biofilm formation, a total of 8 stents (4 shams, 4 CSSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO-1. Animals were assessed 2 weeks after stent insertion with nasal endoscopy, sinus culture, computed tomography (CT) scan, histopathology, and scanning electron microscopy (SEM). RESULTS: PAO-1 biofilm formation was significantly reduced in vitro with exposure to the CSS (p < 0.0001). Insertion of the stent in PAO-1-infected rabbits for 2 weeks resulted in significant improvement in sinusitis according to endoscopy scoring (p < 0.0001) and CT scoring (p < 0.002). Histology and SEM revealed marked improvement in the structure of the mucosa and submucosa with no detection of biofilm structures in the CSS cohort. CONCLUSION: Although this study had a small sample size, we identified robust therapeutic efficacy of the CSS by reducing bacterial load and biofilm formation of P aeruginosa in a preclinical model of sinusitis after placement for 2 weeks.