Abstract-Although stimulation of the ␤-adrenergic receptor increases levels of cAMP and activation of the cAMP response element (CRE) in cardiac myocytes, the role of the signaling mechanism regulated by cAMP in hypertrophy and apoptosis is not well understood. In this study we show that protein expression of inducible cAMP early repressor (ICER), an endogenous inhibitor of CRE-mediated transcription, is induced by stimulation of isoproterenol (ISO), a ␤-adrenergic agonist with a peak at Ϸ12 hours and persisting for more than 24 hours in neonatal rat cardiac myocytes. ICER is also upregulated by phenylephrine but not by endothelin-1. Continuous infusion of ISO also increased ICER in the rat heart in vivo. Overexpression of ICER significantly attenuated ISO-and phenylephrine-induced cardiac hypertrophy but did not inhibit endothelin-1-induced cardiac hypertrophy. Overexpression of ICER also stimulated cardiac myocyte apoptosis. Antisense inhibition of ICER significantly enhanced ␤-adrenergic hypertrophy, whereas it significantly inhibited ␤-adrenergic cardiac myocyte apoptosis, suggesting that endogenous ICER works as an important regulator of cardiac hypertrophy and apoptosis. Inhibition of CRE-mediated transcription by dominant-negative CRE binding protein inhibited cardiac hypertrophy, whereas it stimulated cardiac myocyte apoptosis, thereby mimicking the effect of ICER. Both ISO and ICER reduced expression of Bcl-2, an antiapoptotic molecule, whereas antisense ICER prevented ISO-induced downregulation of Bcl-2. These results suggest that ICER is upregulated by cardiac hypertrophic stimuli increasing CRE-mediated transcription in cardiac myocytes and acts as a negative regulator of hypertrophy and a positive mediator of apoptosis, in part through both inhibition of CRE-mediated transcription and downregulation of Bcl-2. Key Words: cardiac hypertrophy Ⅲ apoptosis Ⅲ gene regulation Ⅲ cell signaling/signal transduction A ccumulating evidence suggests that chronic stimulation of ␤-adrenergic receptor (␤-AR) in patients causes progressive cardiac dysfunction, cell loss, and cardiac chamber remodeling. Consistent with this notion, it has been demonstrated that stimulation of the ␤-AR causes hypertrophy and apoptosis in cardiac myocytes. [1][2][3][4] Thus, understanding the signaling mechanism that mediates growth and death of cardiac myocytes by ␤-AR stimulation may lead to a better treatment for patients with heart failure.Although cAMP is one of the most well-known signaling molecules activated by ␤-AR stimulation, 5 its mechanism of action in cardiac hypertrophy and apoptosis is not fully understood. Increased production of cAMP by enhanced activities of adenylyl cyclase leads to activation of protein kinase A (PKA), which in turn causes phosphorylation/activation of cAMP response element (CRE) binding protein (CREB) and subsequent gene expression through CRE-mediated transcription. 6 It has recently been shown that activation of PKA in the mouse heart causes cardiac myocyte hypertrophy and dilated cardiomyopathy...

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Open or minimally invasive cystectomy is a complex, morbid procedure. Urinary diversion is a significant contributor to complications, as is patient comorbidity. Although patients with an ileal conduit had more comorbidities, they experienced fewer complications than those with an orthotopic bladder substitute or Indiana pouch diversion.

A modified version of the Female Sexual Function Index (FSFI) was used to assess the prevalence of FSD in 587 patients who completed the questionnaire. Logistic regression was used to identify risk factors. RESULTSThe prevalence of FSD was 63%; age, menopausal status and usage of selective serotonin reuptake inhibitors were statistically significant risk factors for FSD. CONCLUSIONSFSD is highly prevalent in this population of patients and screening female urological patients for FSD should be considered. OBJECTIVETo determine the prevalence of and risk factors for female sexual dysfunction (FSD) in a practice focused mainly on female urology.