Search

Erectile dysfunction (ED) is a major health problem worldwide and affects approximately 75% of diabetic patients, likely due to severely damaged cavernous body. While screening for cytokines produced by adipose tissue-derived stem cells, we detected neuromedin B (NMB). To explore a potential treatment option for ED, we examined whether NMB was capable of restoring erectile function. We also examined the potential mechanism by which NMB could restore erectile function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. An adenovirus expressing NMB (AdNMB) was injected into the penis 6 weeks after STZ administration. Four weeks after the injection of AdNMB, erectile function, penile histology, and protein expression were analyzed. As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein. This restoration was associated with conservation of the cavernous body structure and neural nitric oxide synthase (nNOS)-expressing nerves, together with recovery of α-smooth muscle actin, vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons. Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves. NMB may be useful to treat ED patients with a severely damaged cavernous body. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a major health problem, particularly in the elderly population, which is rapidly increasing. It is necessary to elucidate the mechanism by which ED occurs in the elderly. Cellular senescence is commonly detected in old tissues, and it is well known that senescent cells not only withdraw from the cell cycle but also remain viable and actively produce a variety of cytokines. We examined the effect of senescent cells on erectile function after injection of senescent cells into the penises of mice. Human umbilical vein endothelial cells were infected with an adenovirus expressing a constitutively active mutant of Ras to induce senescence, and were injected into the penises of nude mice. These senescent cells expressed proinflammatory cytokines such as interleukin-1β (IL-1β). Injection of senescent cells impaired erectile function, as assessed by the measurement of intracavernous pressure. Although the structure of the cavernous body did not remarkably change, expression of the catalytically active form of endothelial nitric oxide synthase and that of total neural nitric oxide synthase significantly decreased after injection. The penises injected with the senescent cells expressed human IL-1β and subsequently endogenous proinflammatory cytokines such as mouse IL-1β and tumor necrosis factor-α. These results suggested that senescent cells impaired erectile function through induction of endothelial dysfunction and nerve injury. These effects may be mediated by proinflammatory cytokines produced by senescent cells. [ABSTRACT FROM AUTHOR]

'LEOPIN ROYAL®' (LER), a non-prescription health-promoting medication in Japan, is a preparation containing six natural medicines, namely, aged garlic extract, ginseng, oriental bezoar, velvet antler, cuscuta seed and epimedium herb. To determine the effect of LER on symptoms of aging in males, we conducted an open-labeled, randomized clinical trial using Kampo (mainly kamishoyosan) as a control. Forty-nine male patients (age, 62.7 (SD 11.8) years) with mild or more pronounced symptoms of aging were enrolled and randomly assigned to the LER ( n = 24) or Kampo group ( n = 25) for 6 months. The Aging Males' Symptoms (AMS) scale and the International Index of Erectile Function with 5 questions (IIEF-5) were tested at baseline, and after 3 and 6 months of administration of the medications. In the AMS scale, the somatic and psychological sub-scores and total score decreased depending on the time course in both groups. However, the decrease in the slope of the LER group was greater than that of the Kampo group. There was a significant difference between the groups and the group and month interaction (G × M), as revealed by a linear mixed model analysis ( p < 0.05). The IIEF-5 score increased in the LER group ( p = 0.02 with regard to G × M). In conclusion, the present results indicate that LER is possibly superior to mainly kamishoyosan on the rate of improvement of symptoms of aging, including erectile dysfunction, in males. [ABSTRACT FROM AUTHOR]

Introduction Erectile dysfunction ( ED) is a major health problem. We have shown that adrenomedullin ( AM) restores erectile function in diabetic rats. Aim The aim of this study is to explore a better treatment for ED, we examined whether combination of AM and angiopoietin-1 ( Ang-1) was more effective to treat ED than treatment with AM alone or Ang-1 alone. We also compared the effect of the combination therapy with that of treatment with vascular endothelial growth factor- A ( VEGF-A). Methods Male Wistar rats were injected with streptozotocin ( STZ) to induce diabetes. Adenoviruses expessing AM ( AdAM), Ang-1 ( AdAng-1), and VEGF-A ( AdVEGF-A) were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology, and protein expression were analyzed 4 weeks after the injection of the adenoviruses. Main Outcome Measures Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of α-smooth muscle actin ( SMA), VE-cadherin and type I collagen was assessed by Western blot analysis. Results Infection with AdAM plus AdAng-1 more effectively restored erectile function than infection with AdAM alone or AdAng-1 alone. This combination therapy restored erectile function to a level similar to that observed in the age-matched Wistar rats. Expression of SMA and VE-cadherin increased more significantly in the AdAM plus AdAng-1-treated group than in the AdAM- or AdAng-1-treated group. Although AdVEGF-A infection restored erectile function significantly, it also caused enlargement of the trabeculae of the cavernous body, aberrant angiogenesis, and overproduction of type I collagen. Conclusions These results suggested that combination therapy with AM and Ang-1 potently restored erectile function and normal morphology of the cavernous body compared with VEGF-A administration. This combination therapy will be useful to treat ED patients with a severely damaged cavernous body. Nishimatsu H, Suzuki E, Nomiya A, Niimi A, Suzuki M, Fujimura T, Fukuhara H, and Homma Y. Adrenomedullin and angiopoietin-1 additively restore erectile function in diabetic rats: Comparison with the combination therapy of vascular endothelial growth factor and angiopoietin-1. J Sex Med **;**:**-**. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to assess the association between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) using the Core Lower Urinary Tract Symptom Score (CLSS) and the International Index of Erectile Dysfunction (IIEF)-5 questionnaires. Methods: A total of 220 consecutive treatment-naive men completed the International Prostate Symptom Score (IPSS), CLSS, and IIEF-5 questionnaires. The clinical diagnoses were benign prostate hyperplasia (BPH, n = 58), prostatic cancer ( n = 51), prostatitis ( n = 28), overactive bladder wet (OAB wet, n = 16), other diagnoses ( n = 39), and controls ( n = 28). Simple statistics and predictability of low IIEF-5 score were examined. Results: The total IIEF-5 score significantly correlated with both the IPSS and CLSS questionnaires ( p = 0.0001). Among IPSS and CLSS symptoms, factors other than daytime frequency and incomplete emptying showed significant correlation with the total IIEF-5 score. A multivariate regression model indicated nocturia and urethral pain as independent factors for low IIEF-5 scores. Conclusion: Urethral pain was identified as an independent factor for erectile dysfunction. The extraction of pain symptoms using CLSS questionnaire may be useful to evaluate LUTS in men with pelvic health problems. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. Erectile dysfunction (ED) is a major health problem. It is known that diabetic patients are more refractory to common treatments for ED. Aim. To explore the better treatment for ED, we examined the effects of adipose-derived stem cells (ASC) on ED using a diabetic rat model. We also analyzed the cytokines produced by ASC and implicated in ASC-induced restoration of erectile function. Methods. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. ASC or adenoviruses were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology and protein expression were analyzed 4 weeks after the injection of ASC or adenoviruses. Main Outcome Measures. Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of proteins specific for vascular endothelial cells (VEC) was assessed by Western blot analysis. Results. ASC restored erectile function especially when they were cultured in medium containing growth factors for VEC. This restoration was associated with improvement in the histology of the cavernous body, and increased expression of VEC markers such as VE-cadherin and endothelial nitric oxide synthase (eNOS). When the expression of adrenomedullin (AM), a vasoactive peptide originally isolated from human pheochromocytoma tissue, was knocked down, the effect of ASC on ED was significantly diminished. Knockdown of AM was associated with decreased expressions of VE-cadherin and eNOS. Furthermore, overexpression of AM induced by adenovirus infection significantly improved erectile function in these diabetic rats. Overexpression of AM was associated with increased expressions of VE-cadherin and eNOS. Conclusions. These results suggested that ASC have the potentials to restore erectile function and that AM produced by ASC plays a major role in the restoration of erectile function. Nishimatsu H, Suzuki E, Kumano S, Nomiya A, Liu M, Kume H, and Homma Y. Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of erectile function in diabetic rats. J Sex Med 2012;9:482-493. [ABSTRACT FROM AUTHOR]