Functional investigations of thromboxane synthase (CYP5A1) in lipid bilayers of nanodiscs.

CYP5A1 is a membrane-associated cytochrome P450 that metabolizes the cyclooxygenase product prostaglandin (PGH2 ) into thromboxane A2 (TXA2 ), a potent inducer of vasoconstriction and platelet aggregation. Although CYP5A1 is an ER-bound protein, the role of membranes in modulating the thermodynamics and kinetics of substrate binding to this protein has not been elucidated. In this work, we incorporated thromboxane synthase into lipid bilayers of nanodiscs for functional studies. We measured the redox potential of CYP5A1 in nanodiscs and showed that the redox potential is within a similar range of other drug-metabolizing P450 enzymes in membranes. Further, we showed that binding of substrate to CYP5A1 can induce conformational changes in the protein that block small-molecule ligand egress by measuring the kinetics of cyanide binding to CYP5A1 as a function of substrate concentration. Notably, we observed that sensitivity to cyanide binding was different for two substrate analogues, U44069 and U46619, thus indicating that they bind differently to the active site of CYP5A1. We also characterized the effects of the different lipids on CYP5A1 catalytic activity by using nanodiscs to create unary, binary, and ternary lipid systems. CYP5A1 activity increased dramatically in the presence of charged lipids POPS and POPE, as compared to the unary POPC system. These results suggest the importance of lipid composition on modulating the activity of CYP5A1 to increase thromboxane formation.

Maxillary Sinus Anatomy and Physiology.

This study summaries the anatomy, including neurovascular anatomy, and physiology of the maxillary sinus. As the maxillary sinus is intimately related to the maxillary dentition, the maxillary sinus is the first paranasal sinus to become involved in infections of dental origin. Not only are these infections often very symptomatic but also spread to neighboring paranasal sinuses and extrasinus tissues such as the skin and the orbit.

The Airway Pocket: Novel Advancement in Endoscopic Submucosal Placement of Posterior Cartilage Graft.

Endoscopic technology has increased our options for treatment of airway stenosis in a minimally invasive manner. This novel technique advances endoscopic posterior graft placement by creation of an airway pocket, potentially reducing risk of graft migration and improving outcomes. Laryngoscope, 134:3402-3405, 2024.

Utilization and trends in surgical instrument use in pediatric adenotonsillectomy.

OBJECTIVE: Examine trends in surgical instrument usage for pediatric adenotonsillectomy. METHODS: An online survey asking questions about current and previous surgical instrument use was created by the authors and distributed to 517 members of the American Society of Pediatric Otolaryngology in October 2015. The survey was designed to assess trends in the use of surgical instruments in pediatric adenotonsillectomy by comparing the results of our 2015 survey to data from a previously published 2005 study. RESULTS: 133 surveys were returned. The most common instruments for total tonsillectomy in 2015 were monopolar electrocautery (57.0%) and coblation (22.7%). The most common subtotal tonsillectomy instruments in 2015 were microdebrider with monopolar electrocautery (41.3%) and coblation (37.0%). The most common adenoidectomy instruments in 2015 were monopolar electrocautery alone (41.3%), coblation (15.1%), and microdebrider with electrocautery (15.1%). CONCLUSION: As compared to our 2005 study, our 2015 study demonstrates that the instrument choice for total tonsillectomy, sub-total tonsillectomy, and adenoidectomy have shifted away from cold techniques toward monopolar electrocautery and coblation.