The Differential Absorption of a Series of P-Glycoprotein Substrates in Isolated Perfused Lungs from Mdr1a/1b Genetic Knockout Mice can be Attributed to Distinct Physico-Chemical Properties: an Insight into Predicting Transporter-Mediated, Pulmonary Specific Disposition.

Purpose: To examine if pulmonary P-glycoprotein (P-gp) is functional in an intact lung; impeding the pulmonary absorption and increasing lung retention of P-gp substrates administered into the airways. Using calculated physico-chemical properties alone build a predictive Quantitative Structure-Activity Relationship (QSAR) model distinguishing whether a substrate's pulmonary absorption would be limited by P-gp or not.

Methods: A panel of 18 P-gp substrates were administered into the airways of an isolated perfused mouse lung (IPML) model derived from Mdr1a/Mdr1b knockout mice.

Absorption of ipratropium and l-carnitine into the pulmonary circulation of the ex-vivo rat lung is driven by passive processes rather than active uptake by OCT/OCTN transporters.

The organic cation transporters OCT and OCTN have been reported to play a significant role in the cellular uptake of substrates within in vitro lung cells. However, no studies to date have investigated the effect of these transporters upon transepithelial absorption of substrates into the pulmonary circulation. We investigated the contribution of OCT and OCTN transporters to total pulmonary absorption of l-carnitine and the anti-muscarinic drug, ipratropium, across an intact isolated perfused rat lung (IPRL).

Selectivity in the impact of P-glycoprotein upon pulmonary absorption of airway-dosed substrates: a study in ex vivo lung models using chemical inhibition and genetic knockout.

P-glycoprotein (P-gp) mediated efflux is recognised to alter the absorption and disposition of a diverse range of substrates. Despite evidence showing the presence of P-gp within the lung, relatively little is known about the transporter's effect upon the absorption and distribution of drugs delivered via the pulmonary route. Here, we present data from an intact isolated rat lung model, alongside two isolated mouse lung models using either chemical or genetic inhibition of P-gp.

Relativistic positron creation using ultraintense short pulse lasers.

We measure up to 2x10;{10} positrons per steradian ejected out the back of approximately mm thick gold targets when illuminated with short ( approximately 1 ps) ultraintense ( approximately 1x10;{20} W/cm;{2}) laser pulses. Positrons are produced predominately by the Bethe-Heitler process and have an effective temperature of 2-4 MeV, with the distribution peaking at 4-7 MeV. The angular distribution of the positrons is anisotropic.

Optical properties in nonequilibrium phase transitions.

An open question about the dynamical behavior of materials is how phase transition occurs in highly nonequilibrium systems. One important class of study is the excitation of a solid by an ultrafast, intense laser. The preferential heating of electrons by the laser field gives rise to initial states dominated by hot electrons in a cold lattice.

High-repetition-rate grazing-incidence pumped x-ray laser operating at 18.9 nm.

We have demonstrated a 10 Hz Ni-like Mo x-ray laser operating at 18.9 nm with 150 mJ total pump energy by employing a novel pumping scheme. The grazing-incidence scheme is described, where a picosecond pulse is incident at a grazing angle to a Mo plasma column produced by a slab target irradiated by a 200 ps laser pulse.

Single-state measurement of electrical conductivity of warm dense gold.

We report on a single-state measurement of electrical conductivity of warm dense gold in the solid to plasma transition regime. This is achieved using the idealized slab plasma approach of isochoric heating of ultrathin samples by a femtosecond laser, coupled with femtosecond probe measurements of reflectivity and transmission. The experiment also reveals the time scale associated with the disassembly of laser heated solid.

Isochoric heating of solid-density matter with an ultrafast proton beam.

A new technique is described for the isochoric heating (i.e., heating at constant volume) of matter to high energy-density plasma states (>10(5) J/g) on a picosecond time scale (10(-12)sec).

1.1-J, 120-fs laser system based on Nd:glass-pumped Ti:sapphire.

We have developed an ultrashort-pulse laser system in which the final Ti:sapphire amplifier stage is pumped by the frequency-doubled output of a Nd:glass laser. The laser produces pulses with an energy in excess of 1 J on target and an estimated peak focused irradiance of 5 x 10(19) W/cm(2).