Effects of endoscopic sinus surgery on nasal spray deposition using dye-based methods for humans and a human silicone sinonasal cavity model.

OBJECTIVE: We have evaluated that the deposition patterns of corticosteroid nasal spray in the sinonasal cavity of both post-operated human cases, which were further compared with a computed tomography-based sinonasal airway model. METHODS: Fifty-one patients with chronic rhinosinusitis following an endoscopic sinus surgery were enrolled in this study. Nasal spray mometasone furoate hydrate (Nasonex®) containing 0.1% indigocarmine was applied to the patients' nasal cavities and the sinonasal cavity was observed by endoscopy and video documentation. A single plaster sinonasal model was used to quantify the sinonasal deposition of nasal sprays containing 10% red ink solution using 12 round paper strips. RESULTS: The predominant areas of the spray deposition of the operated sinonasal cavities were recognized in the ethmoid sinus and the olfactory cleft in the human study. The droplets were mainly deposited in the inferior turbinate followed by the posterior part of the ethmoid sinus, the olfactory cleft, and anterior part of the ethmoid sinus in a sinonasal model. CONCLUSION: The corticosteroid nasal spray efficiently reached the olfactory cleft and the ethmoid sinus in post-operative conditions, which was demonstrated by post-operated human cases and a computed tomography-based sinonasal airway model.

The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression.

The Farnesoid X receptor (FXR) regulates bile salt, glucose and cholesterol homeostasis by binding to DNA response elements, thereby activating gene expression (direct transactivation). FXR also inhibits the immune response via tethering to NF-κB (tethering transrepression). FXR activation therefore has therapeutic potential for liver and intestinal inflammatory diseases. We aim to identify and develop gene-selective FXR modulators, which repress inflammation, but do not interfere with its metabolic capacity. In a high-throughput reporter-based screen, mometasone furoate (MF) was identified as a compound that reduced NF-κB reporter activity in an FXR-dependent manner. MF reduced mRNA expression of pro-inflammatory cytokines, and induction of direct FXR target genes in HepG2-GFP-FXR cells and intestinal organoids was minor. Computational studies disclosed three putative binding modes of the compound within the ligand binding domain of the receptor. Interestingly, mutation of W469A residue within the FXR ligand binding domain abrogated the decrease in NF-κB activity. Finally, we show that MF-bound FXR inhibits NF-κB subunit p65 recruitment to the DNA of pro-inflammatory genes CXCL2 and IL8. Although MF is not suitable as selective anti-inflammatory FXR ligand due to nanomolar affinity for the glucocorticoid receptor, we show that separation between metabolic and anti-inflammatory functions of FXR can be achieved.