Introduction Metabolic syndrome (MetS) is the most important public health issue threatening the health of men and women all over the world. Its current prevalence (i.e., approximately 30%) is continuously increasing. MetS by itself is considered a risk factor for erectile dysfunction (ED). Aim To focus on the definition epidemiology, pathogenesis, and possible mechanistic links between MetS and ED in order to provide guidelines for treating such individuals. Methods The search strategies yielded total records screened from PubMed. Main Outcome Measures Regardless of the definition, MetS consists of insulin resistance, hypertension, dyslipidemia, and obesity. MetS is not an end disease but is a disorder of energy utilization and storage. Results The prevalence of ED in patients with MetS is almost twice than in those without MetS, and about 40% of patients with ED have MetS. An important mechanism linking MetS and ED is hypogonadism. Conclusions Recognizing through ED, underlying conditions such as hypogonadism, diabetes and MetS might be a useful motivation for men to improve their health-related choices. The clinical management of MetS can be done by therapeutic interventions that include lifestyle modifications, hormone replacement alone or in combination with phosphodiesterase 5 inhibitors, and other pharmacological treatments.

Acetyl-DL-leucine is a derivative of the branched chain amino acid leucine. In observational clinical studies acetyl-DL-leucine improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder, Niemann-Pick disease type C1. Here, we investigated acetyl-DL-leucine and its enantiomers acetyl-L-leucine and acetyl-D-leucine in symptomatic Npc1-/- mice and observed improvement in ataxia with both individual enantiomers and acetyl-DL-leucine. When acetyl-DL-leucine and acetyl-L-leucine were administered pre-symptomatically to Npc1-/- mice, both treatments delayed disease progression and extended life span, whereas acetyl-D-leucine did not. These data are consistent with acetyl-L-leucine being the neuroprotective enantiomer. Altered glucose and antioxidant metabolism were implicated as one of the potential mechanisms of action of the L enantiomer in Npc1-/- mice. When the standard of care drug miglustat and acetyl-DL-leucine were used in combination significant synergy resulted. In agreement with these pre-clinical data, when Niemann-Pick disease type C1 patients were evaluated after 12 months of acetyl-DL-leucine treatment, rates of disease progression were slowed, with stabilisation or improvement in multiple neurological domains. A beneficial effect of acetyl-DL-leucine on gait was also observed in this study in a mouse model of GM2 gangliosidosis (Sandhoff disease) and in Tay-Sachs and Sandhoff disease patients in individual cases of off-label-use. Taken together, we have identified an unanticipated neuroprotective effect of acetyl-L-leucine and underlying mechanisms of action in lysosomal storage diseases, supporting its further evaluation in clinical trials in lysosomal disorders.

Sandhoff disease is a rare neurodegenerative lysosomal storage disease associated with the storage of GM2 ganglioside in late endosomes/lysosomes. Here, we explored the efficacy of acetyl-DL-leucine (ADLL), which has been shown to improve ataxia in observational studies in patients with Niemann-Pick Type C1 and other cerebellar ataxias. We treated a mouse model of Sandhoff disease (Hexb -/-) (0.1 g/kg/day) from 3 weeks of age with this orally available drug. ADLL produced a modest but significant increase in life span, accompanied by improved motor function and reduced glycosphingolipid (GSL) storage in the forebrain and cerebellum, in particular GA2. ADLL was also found to normalize altered glucose and glutamate metabolism, as well as increasing autophagy and the reactive oxygen species (ROS) scavenger, superoxide dismutase (SOD1). Our findings provide new insights into metabolic abnormalities in Sandhoff disease, which could be targeted with new therapeutic approaches, including ADLL.

Silodosin improves erectile function in obstructed rats. Further clinical trials are needed to explore fully the potential benefits of silodosin in patients with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in association with ED. Neurourol. Urodynam. 36:597-603, 2017. © 2016 Wiley Periodicals, Inc.

These results suggest that HUCB-MNC treatment can enhance the recovery of erectile function and promote numerous activities such the contribution of the hypoxia-inducible factor-1α and von Willebrand factor pathway to the neurogenic erectile response of diabetic rats. HUCB-MNCs in the healing process could involve an adaptive regenerative response and appear to be a potential candidate for cell-based therapy in ED of men with diabetes. It is evident that HUCB could provide a realistic therapeutic modality for the treatment of diabetic ED.

Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis. This review aims to identify the mechanisms of ED in the penile aging process in experimental and clinical data. It also highlights areas that are in need of more research. The search strategies yielded total records screened from PubMed. Clarification of the molecular mechanisms that accompanies corpus cavernosum aging and aging-associated ED will aid new perspectives in the development of novel mechanism-based therapeutic approaches. Age is not a limiting factor for ED medical management, and it is never too late to treat. Hypogonadism should be managed regardless of age, and synergistic effects have been found during testosterone (T) replacement therapy when used along with oral phosphodiesterase-5 (PDE-5) inhibitors. Therefore, the clinical management of ED related to aging can be done by therapeutic interventions that include PDE-5 inhibitors, and other pharmacological treatments.

Erectile dysfunction (ED) is associated with diabetes mellitus (DM). Pomegranate juice (PJ) is a potent antioxidant in diabetes induced oxidative stress. The aim of this study was to evaluate whether the administration of PJ ameliorates ED in streptozotocin (STZ)-diabetic rat model. Adult male Sprague-Dawley rats were divided into three groups (n=10-12, each): (1) Control, (2) STZ (25-35 mg kg, intravenously, 10 weeks) induced DM, and (3) PJ (100 mg kg day, 10 weeks) treated DM rats. The in vivo erectile [a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP)] and ex vivo corpus cavernosum (CC) responses were evaluated. Immunohistochemistry and Masson's trichrome staining were performed. Malondialdehyde (MDA) levels were measured. The ICP/MAP value in diabetic rats was lower than controls, which was partially improved by PJ treatment. Electrical field stimulation (EFS)-induced relaxant responses in CC from the diabetic group were significantly decreased that were ameliorated by treatment. Phenylephrine- and EFS-induced contractions were not altered in diabetic rats. PJ treatment normalized raised MDA levels of diabetic CC samples. Although the intensities of endothelial nitric oxide synthase (NOS) and neuronal NOS enzymes were decreased, inducible NOS protein levels were stronger in diabetic slides than controls. This is the first study to show that PJ treatment ameliorates partially ED and completely oxidative stress and fibrosis in a diabetic rat model. Our results highlight the success of antioxidant mechanism of PJ in ED with diabetes and open the way for future understanding in alternative treatment combinations with PDE5 inhibitors.

Niemann-Pick disease type C (