Introduction Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). Aim The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couple’s relationship predict incident MACE. Methods A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. Main Outcome Measures Information on MACE was obtained through the City of Florence Registry Office. Results During a mean follow-up of 4.3 ± 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10–2.78; P <0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR=2.67 [1.42–5.04] and 1.57 [1.01–2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P <0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. Conclusions The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.

Introduction Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Aim To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). Main Outcome Measures PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. Methods In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Results In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. Conclusions The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil.

Although it is well established that all the aspects of male reproduction are hormonally regulated, the endocrine control of the ejaculatory reflex is still not completely clarified. Sex steroids, thyroid and pituitary hormones (oxytocin and prolactin) have been proposed to control the ejaculatory process at various levels; however, only a few reports are currently available. The aim of this study was to evaluate the contribution of testosterone, thyrotropin (TSH) and prolactin (PRL) in the pathogenesis of ejaculatory dysfunction in a large series of subjects consulting for sexual dysfunction. Among the 2652 patients studied, 674 (25.2%) and 194 (7.3%) reported premature and delayed ejaculation (PE and DE), respectively. Categorizing ejaculatory difficulties on an eight-point scale starting from severe PE and ending with anejaculation (0 = severe PE, 1 = moderate PE, 2 = mild PE, 3 = no difficulties, 4 = mild DE, 5 = moderate DE, 6 = severe DE and 7 = anejaculation), PRL as well as TSH levels progressively increased from patients with severe PE towards those with anejaculation. Conversely, the opposite was observed for testosterone levels. All of these associations were confirmed after adjustment for age (adjusted r = 0.050, 0.053 and -0.038 for PRL, TSH and testosterone, respectively; all p < 0.05). When all hormonal parameters were introduced in the same regression model, adjusting for age, ΣMHQ (an index of general psychopathology) and use of selective serotonin reuptake inhibitor antidepressants, they were independently associated with ejaculatory problems (adjusted r = 0.056, 0.047 and -0.059 for PRL, TSH and testosterone, respectively; all p < 0.05). This study indicates endocrine system is involved in the control of ejaculatory function and that PRL, TSH and testosterone play an independent role.

Introduction Although testosterone (T) has been suggested to play a protective role against the development of atherosclerosis, studies demonstrating an association between low T and incident major adverse cardiovascular events (MACE) are scanty in the general population and absent in subjects with erectile dysfunction (ED). Aim To investigate whether low T in subjects with ED predict incident fatal or nonfatal MACE. Methods This is an observational prospective cohort study evaluating a consecutive series of 1687 patients attending our andrological unit for ED. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY) and ANDROTEST structured interviews measuring components relative to ED and hypogonadal-related symptoms, respectively. Main Outcome Measures Total T was evaluated at baseline. Information on MACE was obtained through the City of Florence Registry Office. Results Among the patients studied, 5.2, 13.8, and 22.4% were hypogonadal according to different thresholds (T&lt;8, 10.4 and 12 nmol/L or 230, 300 and 350 ng/dL, respectively). During a mean follow-up of 4.3 ± 2.6 years, 139 MACE, 15 of which were fatal, were observed. Unadjusted incidence of MACE was not associated with T levels. Conversely, the proportion of lethal events among MACE was significantly higher in hypogonadal patients, using either 10.4 nmol/L (300 ng/dL) or 8 nmol/L (230 ng/dL) thresholds. However, after adjustment for age and Chronic Diseases Score in a Cox regression model, only the association between incident fatal MACE and T&lt;8 nmol/L (230 ng/dL) was confirmed (HR=7.1 [1.8–28.6]; P &lt;0.001). Interestingly, measuring hypogonadal-related symptoms and signs through ANDROTEST, only fatal MACE were also associated with a higher score (HR=1.2 [1.0–1.5] for each ANDROTEST score increment; P = 0.05 after adjustment for age and Chronic Diseases Score). Conclusions T levels are associated with a higher mortality of MACE. The identification of low T levels should alert the clinician thus identifying subjects with an increased cardiovascular risk.

We reviewed the world literature on solitary fibrous tumors of the central nervous system from August 1996 to July 2011, focusing on both clinicopathological features and diagnostic findings. The anatomical distribution of the 220 cases reported so far reveals that most are intracranial and just over one-fifth are intraspinal. In decreasing frequency, intracranial tumors involve the supratentorial and infratentorial compartments, the pontocerebellar angle, the sellar and parasellar regions, and the cranial nerves. Intraspinal tumors are mainly located in the thoracic and cervical segments. Although most solitary fibrous tumors of the central nervous system are dural based, a small subset presents as subpial, intraparenchymal, intraventricular, or as tumors involving the nerve rootlets with no dural connection. Preoperative imaging and intraoperative findings suggest meningioma, schwannoma or neurofibroma, hemangiopericytoma, or pituitary tumors. Immunohistochemistry is critical to establish a definitive histopathological diagnosis. Vimentin, CD34, BCL2, and CD99 are the most consistently positive markers. The usual histologic type generally behaves in a benign manner if complete removal is achieved. Recurrence is anticipated when resection is subtotal or when the tumor exhibits atypical histology. The proliferative index as assessed by MIB1 labeling is of prognostic significance. Occasionally, tumors featuring conventional morphology may recur, perhaps because of minimal residual disease left behind during surgical extirpation. Rare extracranial metastases and tumor-related deaths are on record. Surgery is the treatment of choice. Stereotactic and external beam radiation therapy may be indicated for postsurgical tumor remnants and for unresectable recurrences. Long-term active surveillance of the patients is mandatory.

Introduction Previous clinical studies on effect of statins treatment on testosterone (T) levels have produced mixed results. Aim The aim of the present study is to evaluate the association between statin therapy and hormonal parameters in a large series of subjects seeking medical care at our unit for erectile dysfunction (ED). Methods A consecutive series of 3,484 (mean age 51.6 ± 13.1 years) patients with ED was studied. Main Outcome Measures Several hormonal and biochemical parameters were investigated, along with ANDROTEST structured interview measuring hypogonadism-related symptoms. Results Among the patients studied, 244 (7%) patients were being treated with statins. After adjustment for confounding factors (including body mass index and Progetto Cuore cardiovascular (CV) risk engine score), both total and calculated free testosterone levels were significantly lower in subjects taking statins, when compared to the rest of the sample (hazard ratio [HR]=0.93 [0.90; 0.96] and 0.26 [0.01; 0.18] for each decrement of total T and calculated free T, respectively; both P &lt;0.0001). The use of statins was also associated with a reduced testis volume and a higher prevalence of hypogonadism-related symptoms and signs, as assessed by higher ANDROTEST score (HR=1.12 [1.03; 1.21]; P &lt;0.01 after adjustment for confounders). Follicle-stimulating hormone levels were significantly higher in subjects treated with statins when compared to the rest of the sample, while there was a trend toward higher luteinizing hormone levels, but this did not reach statistical significance. The lower levels of total and calculated free T observed in subjects treated with statins were also confirmed comparing them with age-waist circumference and CV risk score matched controls. Finally, subjects being treated with statins showed lower prolactin levels when compared to the rest of the sample. Conclusions Our data demonstrated that statin therapy might induce an overt primary hypogonadism and should be considered as a possible confounding factor for the evaluation of testosterone levels in patients with ED.

No abstract

Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. Indeed, treatment failures are triggered by cancer stem cells (CSCs) that give rise to tumor repopulation upon initial remission. Thus, the role of the heat shock protein TRAP1 in stemness was investigated in CRC cell lines and human specimens, based on its involvement in colorectal carcinogenesis, through regulation of apoptosis, protein homeostasis and bioenergetics. Strikingly, co-expression between TRAP1 and stem cell markers was observed in stem cells located at the bottom of intestinal crypts and in CSCs sorted from CRC cell lines. Noteworthy, TRAP1 knockdown reduced the expression of stem cell markers and impaired colony formation, being the CSC phenotype and the anchorage-independent growth conserved in TRAP1-rich cancer cells. Consistently, the gene expression profiling of HCT116 cells showed that TRAP1 silencing results in the loss of the stem-like signature with acquisition of a more-differentiated phenotype and the downregulation of genes encoding for activating ligands and target proteins of Wnt/β-catenin pathway. Mechanistically, TRAP1 maintenance of stemness is mediated by the regulation of Wnt/β-catenin signaling, through the modulation of the expression of frizzled receptor ligands and the control of β-catenin ubiquitination/phosphorylation. Remarkably, TRAP1 is associated with higher expression of β-catenin and several Wnt/β-catenin target genes in human CRCs, thus supporting the relevance of TRAP1 regulation of β-catenin in human pathology. This study is the first demonstration that TRAP1 regulates stemness and Wnt/β-catenin pathway in CRC and provides novel landmarks in cancer biology and therapeutics.