Detrusor overactivity induced by intravesical application of adenosine 5 '-triphosphate under different delivery conditions in rats

Objectives. We investigate the effects of intravesical application of adenosine 5'-triphosphate (ATP) on bladder activity to elucidate the role of urothelial barrier function and ecto-ATPase activity in the ATP-mediated mechanism inducing detrusor overactivity. Methods. Continuous cystometry by an intravesical catheter inserted from the bladder dome was performed in conscious female rats. Results. ATP solutions adjusted to pH 6.0 did not elicit significant detrusor overactivity at a concentration of 60 mM. However, in bladders pretreated with protamine sulfate (10 mg/mL) to increase urothelial permeability, ATP solution (pH 6.0) induced detrusor overactivity by decreasing the intercontraction intervals. These irritant effects of ATIP after protamine treatment were antagonized by P2X receptor antagonists, such as pyridoxal-5-phosphate-6-azophenyl-2',4-disulfonic acid (70 mu mol/kg) and 2',3'-O-(2,4,6, trinitrophenyl) ATP (30 mu mol/kg). These were also suppressed in rats pretreated with systemic capsaicin (125 mg/kg subcutaneously). Alpha,beta-methylene ATP (5 mM, pH 6.0) or ATP (60 mM, pH6) after intravesical infusion of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (5 mM, pH 6.0), an ecto-ATPase inhibitor, induced detrusor overactivity without protamine pretreatment, but the reduction in intercontraction intervals was smaller compared with that with ATP after protamine treatment. Conclusions. Low permeability of bladder epithelium and ecto-ATPase activity can prevent ATP activation of subepithelial P2X receptors to induce bladder overactivity. Thus, enhanced penetration of endogenous ATIP owing to urothelial damage may contribute to urinary frequency and bladder pain in hypersensitive bladder disorders such as interstitial cystitis.</p

The Predictive Power of Gold in Times before Financial Crisis

The goal of this paper is to figure out if the gold price has predictive power in times preceding financial crisis. For the analysis, The Great Depression, the 1980s, the technology bubble of the late 1990s, and the Global Finanical Crisis were used. The change in the gold price was regressed upon lags of the S&P 500 and lags of the gold price; and the S&P 500 change was regressed upon lags of the gold price and itself. Ultimately, the gold price was found to have very slight predictive power if any but is far less effective than the yield curve