Tobramycin Pharmacokinetics in Pediatric Patients With Primary Ciliary Dyskinesia.

Background: Patients with primary ciliary dyskinesia (PCD) are commonly treated for pulmonary exacerbations with intravenous tobramycin, but data on tobramycin pharmacokinetics in PCD is lacking. The objective of this study was to compare tobramycin pharmacokinetics in pediatric patients with PCD to those with cystic fibrosis (CF).

Methods: This retrospective study included pediatric patients hospitalized for a pulmonary exacerbation between January 2018 and June 2023.

Oleic amide derivatives as small molecule stimulators of the human proteasome's core particle.

A series of oleic acid amide derivatives were synthesized based on our previous and continuing endeavors towards stimulation of the 20S core particle of the proteasome (20S CP) with the goal of increasing the protein degradation rate the ubiquitin-independent pathway. The designed compounds were tested in a variety of biochemical and cell-based assays to assess their ability to increase the rate of hydrolysis of the 20S CP, and compared to a known fatty acid amide stimulator of the 20S CP, AM-404. AM-404 was previously described to stimulate the activity of the 20S CP, however, it does negatively affect viability of cells after prolonged dosing.

Fluorescent Probes with Unnatural Amino Acids to Monitor Proteasome Activity in Real-Time.

The proteasome is an essential protein complex that, when dysregulated, can result in various diseases in eukaryotic cells. As such, understanding the enzymatic activity of the proteasome and what can alter it is crucial to elucidating its roles in these diseases. This can be done effectively by using activity-based fluorescent substrate probes, of which there are many commercially available that target the individual protease-like subunits in the 20S CP of the proteasome.