By using BQ-788 as a selective endothelin ETB-receptor antagonist and FR139317 as a selective endothelin ETA-receptor antagonist, we have characterized the receptor subtypes mediating the systemic and renal vascular effects of endothelin-1 and IRL1620, a selective endothelin ETB-receptor agonist (succinyl-[Glu9,Ala11,5]-endothelin-1(8-21)), in anesthetized rats. Bolus intravenous injection of e...

BACKGROUND AND OBJECTIVE Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p-benzoquinone (p-BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p-BQ is also derived from CS in smokers and it elicits the production ...

BACKGROUND Musculoskeletal pain and low back pain (LBP) in particular is one of the more costly health challenges to society. The STarT Back Tool (SBT) has been developed in the UK with a view to identifying subgroups of LBP patients in order to guide more cost effective care decisions. The Bournemouth Questionnaire (BQ) is a validated multidimensional patient reported outcome measure (PROM) th...

Let P and Q be two complex matrices satisfying P 2 = P and Q = Q. If a, b are nonzero complex numbers such that aP + bQ is diagonalizable, we relation the spectrum of aP + bQ with the spectrum of P −Q, PQ, PQP and PQ−QP .

BACKGROUND Endothelin contributes to the maintenance of vascular tonus in both the systemic circulation and in regional vascular beds. The purpose of the study was to measure the effect of the endothelin A antagonist BQ-123 on renal hemodynamics, tubular function, vasoactive hormones, and blood pressure (BP) in healthy men. METHODS In a randomized, placebo-controlled, double-blind dose-respon...

Inhibition of cytochrome P450 catalytic activity is a principal mechanism for pharmacokinetic drug-drug interactions. Rapid, in vitro testing for cytochrome P450 inhibition potential is part of the current paradigm for identifying drug candidates likely to give such interactions. We have explored the extent that qualitative and quantitative inhibition parameters are dependent on the cytochrome ...

BACKGROUND The vasoactive peptide endothelin 1 (ET-1) acts via two receptors, endothelin receptors A (ET(A)) and B (ET(B)). ET-1 is overexpressed by human cancers in vivo and in vitro and may be mitogenic for cancer cells. METHOD To elucidate if ET-1 is a growth regulator the following were investigated in human colorectal cancer cell lines (LIM1215 and HT29): ET-1 production by ELISA; ET rec...

PURPOSE To investigate whether oxidized low-density lipoprotein (Ox-LDL) affects endothelium-dependent responses in isolated porcine ciliary arteries. METHODS In a myograph system for isometric force measurements, quiescent vessels were incubated with 50 microg/ml, 100 microg/ml, or 200 microg/ml Ox-LDL; 100 microg/ml native LDL (n-LDL); 1 microM of the ET(A)- endothelin receptor antagonist B...

BACKGROUND Myocardial ischemia and reperfusion are associated with increased production of endothelin (ET)-1. METHODS AND RESULTS We examined the effects of BQ-123, a selective ET(A) receptor antagonist, in 80 patients. All patients were randomly allocated to an intracoronary infusion of saline or BQ-123 (6 micromol/L over 20 minutes). The reference group consisted of 20 patients undergoing c...