Erectile dysfunction (ED) affects millions of men throughout the world. The literature is ample, but an accurate estimate of its prevalence is still difficult since figures mainly refer to the USA, and are based mostly on small selected samples of people. Caution must anyway be used in comparing data from studies conducted in the past because of possible differences in the definition and classification of ED. Many factors are believed to contribute to the development and maintenance of ED. The influence of age and of several medical conditions (diabetes, vascular disease, and chronic diseases such as hepatic failure, renal failure and dialysis) is well defined. Also well documented is the role of some drug groups, whereas the role of other pharmacological agents is still controversial because of the frequent coexistence of other pathological conditions or concomitant exposure to other drugs. Less well defined and sometimes controversial is the role of risk factors mainly related to life-style such as cigarette smoking, alcoholism, total cholesterol levels and certain types of trauma. This paper reviews the main data on the epidemiology of ED and some related risk factors.
BXL-628 inhibits RhoA/Rho-kinase signaling, a calcium sensitizing pathway, suggesting its possible clinical use in the treatment of altered bladder contractility often associated with BPH-induced lower urinary tract symptoms.
Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2. Prolonged serum starvation time-dependently pushed bladder stromal cells to express activated myofibroblast markers, such as desmin and smoothelin, without changing other contractile-related proteins and intermediate filaments, such as vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype modification. Because hypertrophy and starvation-induced bladder remodeling are supposed to underlie bladder overactivity, it is possible that BXL-628 might be helpful in reducing not only cumbersome symptoms related to prostate overgrowth, but also those related to bladder irritation.
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