Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: Effect of organic anions and cations

The clearance mechanisms of quinapril and quinaprilat were probed using an isolated perfused rat kidney model. Sixty-four experiments were performed with drug in the absence and presence of classic inhibitors of the organic acid (i.e., probenecid and p-aminohippurate) and organic base (i.e., tetraethylammonium and quinine) transport systems of the proximal tubule. Initial perfusate concentrations of quinapril and quinaprilat were approximately 2.36 μM (or 1000 ng/ml), and transport inhibitors were coperfused at 100–10,000 times the drugs' initial μM concentrations. Quinapril and quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. Perfusate protein binding was determined using an ultrafiltration method at 37°C. Overall, the clearance ratios of quinapril (total renal clearance divided by fu·GFR ) and quinaprilat (urinary clearance divided by fu·GFR ) were significantly reduced, and in a dose-dependent manner, by the coperfusion of organic acids but not organic bases. The data demonstrate that the organic anionic secretory system is the primary mechanism by which quinapril and quinaprilat are transported into and across renal proximal cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45053/1/10928_2006_Article_BF02353517.pd

Optimal Active Control of Structures Using a Screw Jack Device and Linear Quadratic Gaussian Controller

A screw jack is a device which converts input torque into amplified axial force, capitalizing on the device's gearbox mechanism. Traditionally used in auto repair shops, the screw jack has been adapted for the first time for active structural control. The dynamic properties of the device were investigated using open loop control, and the screw jack was found to have a high delay between command and measured force. Numerical simulations and parametric studies of SDOF systems with an LQG-controlled screw jack showed improvements to structural performance at 4 different levels of control effort. Loop simulation method experiments were conducted under seven ground motion records - benefits to structural response were dependent on the type of earthquake, with greater benefits for earthquakes with more low-frequency content. Future work should investigate the types of structures and earthquakes for which the screw jack is most impactful using real-time hybrid simulation.M.A.S