Jakobsen Velazquez (fishmark19)

9 ± 20.9 vs. 116.9 ± 6.0 nmol/g protein). LPA levels also paralleled the progression of renal fibrosis in the renal cortex of Sprague-Dawley rats after unilateral ureteral obstruction (UUO). Administration of an LPA receptor antagonist, Ki16425, reduced the degree of renal fibrosis in UUO rats. These results suggest that the production of renal LPA increases during the development of renal injury and contributes to renal fibrosis. SIGNIFICANCE STATEMENT The present study reveals that the lysophosphatidic acid (LPA) levels increase in the kidney in rat models of hypertension, diabetes, and obstructive nephropathy, and administration of an LPA receptor antagonist attenuates renal fibrosis. Therapeutic approaches that target the formation or actions of renal LPA might be renoprotective and have therapeutic potential.A semimechanistic physiologically based pharmacokinetic (PBPK) model for chloroquine (CQ), a highly lysosomotropic weak base, was applied to digitized rat and human concentration versus time data. The PBPK model in rat featured plasma and red blood cell (RBC) concentrations, extensive and apparent nonlinear tissue distribution, fitted hepatic and renal intrinsic clearances, and a plasma half-life of about 1 day. Tissue-to-plasma CQ ratios at 50 hours after dosing were highest in lung, kidney, liver, and spleen (182-318) and lower in heart, muscle, brain, eye, and skin (11-66). The RBC-to-plasma ratio of 11.6 was assumed to reflect cell lipid partitioning. A lysosome-based extended model was used to calculate subcellular CQ concentrations based on tissue mass balances, fitted plasma, interstitial and free cytosol concentrations, and literature-based pH and pKa values. The CQ tissue component concentrations ranked as follows lysosome > > acidic phospholipid > plasma = interstitial = cytosol ≥ neutral lipids. Thents. Disasters have the potential to cause critical shortages of life-saving equipment. It has been postulated that during patient surge, multiple individuals could be maintained on a single ventilator. This was supported by a previous trial that showed one ventilator could support four sheep. The goal of our study is to investigate if cross contamination of pathological agents occurs between individuals on a shared ventilator with strategically placed antimicrobial filters. A multipatient ventilator circuit was assembled using four sterile, parallel standard tubing circuits attached to four 2 L anaesthesia bags, each representing a simulated patient. Each 'patient' was attached to a Heat and Moisture Exchange filter. An additional bacterial/viral filter was attached to each expiratory limb. 'Patient-Lung' number 1 was inoculated with an isolate of and the circuit was run for 24 hours. Each 'lung' and three points in the expiratory limb tubing were washed with broth and cultured. All cultures were incubated for 48 hours with subcultures performed at 24 hours. Washed cultures of patient 2, 3 and 4 failed to demonstrate growth of . Cultures of the distal expiratory tubing, expiratory limb connector and expiratory limb prefilter tubing yielded no growth of at 24 or 48 hours. Based on this circuit configuration, it is plausible to maintain four individuals on a single ventilator for 24 hours without fear of cross contamination. Based on this circuit configuration, it is plausible to maintain four individuals on a single ventilator for 24 hours without fear of cross contamination.V-Raf murine sarcoma viral oncogene homolog B (BRAF) gene mutations have recently been approved to select advanced stages non-small cell lung cancer (NSCLC) patients for tyrosine kinase inhibitors treatments. In this setting, liquid biopsy may represent a valuable option for BRAF mutational testing in patients without tissue availability. Here, we reviewed 196 plasma based liquid biopsies analysed by an in-house developed next generation sequencing panel, termed Si