modulation of endogenous gene expression via CRISPR/Cas9-mediated 3'UTR editing.

The 3' untranslated regions (UTRs) modulate gene expression levels by regulating mRNA stability and translation. We previously showed that the replacement of the negative regulatory elements from the 3'UTR of glial cell line-derived neurotrophic factor (GDNF) resulted in increased endogenous GDNF expression while retaining its normal spatiotemporal expression pattern. Here, we have developed a methodology for the generation of hyper- and hypomorphic alleles via 3'UTR targeting using the CRISPR/Cas9 system.

Biliary secretion of cefoperazone and its inter-relationship with bile acid transport in the rat.

Cefoperazone is a third generation cephalosporin which is secreted predominantly in bile. This study set out to examine the effect of stimulating bile choleresis on the biliary secretion of cefoperazone. Stimulation of both bile acid-dependent and independent bile flow (phenobarbitone pretreatment) hastened the peak appearance of a pulse of cefoperazone into bile.

Pharmacokinetics and effect on blood pressure of doxazosin in normal subjects and patients with renal failure.

The antihypertensive efficacy and pharmacokinetics of a single 1 mg oral dose of doxazosin were investigated in five healthy male volunteers, six patients with renal failure not on hemodialysis, and four patients with end-stage renal failure studied between two hemodialyses. The dialyzability of doxazosin was studied in five patients. The maximum fall in blood pressure of both volunteers and patients occurred between 4 and 8 hours.