With efforts to reduce cytochrome P450-mediated clearance (CL) during the early stages of drug discovery, transporter-mediated CL mechanisms are becoming more prevalent. However, the prediction of plasma concentration-time profiles for such compounds using physiologically based pharmacokinetic (PBPK) modeling is far less established in comparison with that for compounds with passively mediated ...

Precipitation and temperature are important drivers of soil respiration. The role of moisture and temperature are generally explored at seasonal or inter-annual timescales; however, significant variability also occurs on hourly to daily time-scales. We used small (1.54 m(2)), throughfall exclusion shelters to evaluate the role soil moisture and temperature as temporal controls on soil CO2 efflu...

Although HDL-mediated cholesterol transport to the liver is well studied, cholesterol efflux from hepatocytes back to HDL is less well understood. Real-time imaging of efflux of 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol), which is poorly esterified, and [(3)H]cholesterol, which is extensively esterified, from cultured primary hepatocytes of...

Background and Objective: Efflux pump inhibitors (EPIs) can block efflux pumps and are helpful in potentiating the activity of aminoglycosides against Pseudomonas aeruginosa. The present study compared the effects of phenylalanine-arginine beta naphthylamide (PAβN) and curcumin on aminoglycoside minimum inhibitory concentration (MIC) on Pseudomonas aeruginosa clinical isolates. Materials and M...

Prior studies provide data supporting the notion that ATP binding cassette transporter A1 (ABCA1) promotes lipid efflux to extracellular acceptors in a two-step process: first, ABCA1 mediates phospholipid efflux to an apolipoprotein, and second, this apolipoprotein-phospholipid complex accepts free cholesterol in an ABCA1-independent manner. In the current study using RAW264.7 cells, ABCA1-medi...

OBJECTIVES Enterobacteriaceae have multiple efflux pumps that confer intrinsic resistance to antibiotics. AcrB mediates clinically relevant multidrug resistance and is required for virulence and biofilm formation, making it an attractive target for the design of inhibitors. The aim of this study was to assess the viability of single transporters as a target for efflux inhibition using Salmonell...

To investigate the expression profiles of efflux transporters in human ocular tissues, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to obtain the relative mRNA and protein expressions of various efflux transporters in human ocular tissues. The cornea, conjunctiva, iris-ciliary body (ICB), retina and choroid, human corneal epithelial cell...

BACKGROUND Individuals infected with human immunodeficiency virus (HIV) have decreased high-density lipoprotein (HDL)-cholesterol and increased cardiovascular disease (CVD). Reverse cholesterol transport from macrophages may be inhibited by HIV and contribute to increased CVD. Human studies have not investigated longitudinal effects of HIV and antiretroviral therapy (ART) on cholesterol efflux....

Frog sartorius muscles subjected to overnight loading with Na(+) in K-free Ringer in the cold were subsequently labeled with Na(24) and then immersed in choline Ringer and the efflux of Na(24) followed for 4 hours. The initial efflux of Na(+) appeared to be 17 pmole/cm(2) sec.; this value was maintained for 20 minutes and was followed by an abrupt decline to about 9 pmole/cm(2) sec. This latter...

The accessory genomes of many pathogenic bacteria include ABC transporters that scavenge metal by siderophore uptake and contribute to antimicrobial resistance multidrug efflux. There are mechanistic recently recognized structural similarities between importer proteins efflux pumps. Here we investigated the influence YbtPQ on Klebsiella pneumoniae . is encoded in yersiniabactin cluster a preval...