P-glycoprotein and chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a heterogeneous definition that includes different disease states that usually are associated with abnormal inflammatory responses. Besides being prevalent, the mechanisms involved in its pathogenesis are not clear and there are few therapeutic options with tolerable side effects. P-glycoprotein (P-gp) is an efflux pump responsible of extruding xenobiotics and cellular metabolites from multiple cell types. It has been widely studied in the cancer field, due to its ability to confer resistance to chemotherapy. It also promotes Type 2 helper T-cell polarizing cytokine secretion in CRS and may represent a potential target to differentiate subtypes of CRS and personalize treatment. This state-of-the-art review explores current knowledge on the participation of P-gp in the pathogenesis of CRS, the P-gp inhibition as a novel targeted therapeutic strategy and the exosomal P-gp test, a non-invasive biomarker that can represent an important advance in the field of rhinology.

Bypassing the blood-brian barrier using established skull base reconstruction techniques

Background: Neurological disorders represent a profound healthcare problem accounting for 6.3％ of the global disease burden.Alzheimer's disease alone is expected to impact over 115 million people worldwide by 2050 with a cost of over $1 trillion per year to the U.S.economy.Despite considerable advances in our understanding of the pathogenesis and natural history of neurological disorders, the development of disease modifying therapies have failed to keep pace.This lack of effective treatments is directly attributable to the presence of the blood-brain and blood-cerebrospinal fluid barriers (BBB and BCSFB) which prevent up to 98％ of all potential neuropharmaceutical agents from reaching the central nervous system (CNS).These obstacles have thereby severely limited research and development into novel therapeutic strategies for neurological disease.Current experimental methods to bypass the BBB, including pharmacologic modification and direct transcranial catheter implantation, are expensive, are associated with significant complications, and cannot be feasibly scaled up to meet the chronic needs of a large, aging patient population.Transmucosal drug delivery: An innovative method of direct CNS drug delivery using heterotopic mucosal grafts was described.This method is based on established endoscopic skull base nasoseptal flap reconstruction techniques.The model has successfully demonstrated CNS delivery of chromophore-tagged molecules 1000 times larger than those typically permitted by the BBB.Conclusions: This innovative technique represents the first described method of permanently bypassing the blood-brain barrier using purely autologous tissues.This has the potential to dramatically improve the current treatment of neurological disease by providing a safe and chronic transnasaldelivery pathway for high molecular weight neuropharmaceuticals.