Nicola Caretta

Circulating endothelial progenitor cells in subjects with erectile dysfunction

Erectile dysfunction (ED) is often the first clinical sign of endothelial dysfunction and may precede overt cardiovascular diseases. Bone marrow-derived endothelial progenitor cells migrate into the peripheral circulation to promote endothelial repair. The number of circulating progenitor cells is reduced in patients with cardiovascular risk factor. The objective of our study was to determine the number of these cells in patients with ED both with and without cardiovascular risk factors. These subjects have lower number of circulating progenitor cells, confirming the existence of an endothelial dysfunction and supplying the evidence that ED may be the first symptom of an endothelial damage.

Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction

We evaluated the effect of a chronic treatment with Tadalafil on progenitor cells (PCs) number and endothelial function in patients with erectile dysfunction (ED) with or without cardiovascular risk factors. Twenty-six subjects with ED and 23 aged matched controls were studied. All subjects underwent blood tests, International Index of Erectile Function (IIEF-5), Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), brachial artery flow-mediated dilation (FMD) and PCs count. International index of erectile function, FMD and PC count were re-evaluated in all subjects at the end of Tadalafil and placebo treatment. With respect to controls patients had lower basal FMD (P<0.05) and basal PCs (P<0.05). Treatment with Tadalafil determined a significant increase in PCs (P<0.001) and FMD (P<0.001) with respect to basal level. Positive correlation was found between basal FMD and PCs (P<0.05) and between basal FMD and PCs increase after Tadalafil treatment (P<0.05). Tadalafil promotes a mobilization of PCs and improves endothelial function in ED patients.

Androgens stimulate endothelial progenitor cells through an androgen receptor-mediated pathway

Background and objective  Testosterone (T) treatment has recently been shown to induce an increase in the number of endothelial progenitor cells (EPCs) through a possible effect on bone marrow. Hypogonadotrophic hypogonadal (HH) men have low circulating EPCs that increase significantly after T treatment. Moreover, expression of the androgen receptor (AR) has been demonstrated by immunohistochemistry in these cells, suggesting that T might also have a direct effect on EPC function. In the present study we investigated the expression and function of the AR in human EPCs and the in vitro effect of androgens on EPC function.

Metabolic Syndrome and Erectile Dysfunction: The ultrasound evaluation of cavernosal atherosclerosis

OBJECTIVE To study the relation between metabolic syndrome (MS), cavernosal morphological vasculopathy, and peripheral vascular alterations (carotid and femoral wall) in patients with erectile dysfunction. RESEARCH DESIGN AND METHODS A total of 207 patients and 50 control subjects were evaluated for cardiovascular risk factors, physical examination, reproductive hormones, ultrasound analysis of cavernosal, carotid and femoral arteries (intima-media thickness), and cavernosal flow measurement (peak systolic velocity). RESULTS A total of 28% of patients had MS, and they presented with a high prevalence of cavernosal alterations (70.3%) and systemic vascular impairment (59.3%), whereas patients with cavernosal alterations (44%) showed the higher prevalence of MS (48.9%). The number of MS components was related to the prevalence of penile vasculopathy. However, multivariate analysis showed that MS is not an independent predictor for cavernosal vasculopathy. CONCLUSIONS Patients with cavernosal vasculopathy have an increased cardiometabolic risk, and screening for MS components might identify individuals with a higher risk for cavernosal and systemic atherosclerosis.

PDE-5 inhibitor, Vardenafil, increases circulating progenitor cells in humans.

Bone marrow-derived endothelial progenitor cells (EPCs) originate from haematopoietic stem cells in bone marrow and migrate into the peripheral circulation to promote endothelial repair and neovascularization. The number of circulating progenitor cells is reduced in patients with cardiovascular risk factor. The aim of our study was to determine the number of these cells in healthy patients and to evaluate the effect of Vardenfil, a phosphodiesterases-5 (PDE-5) inhibitor, in the number of circulating EPCs. In our study, we found a significant increase in the number of these cells after the drug administration.

The response to FSH treatment in oligozoospermic men depends on FSH receptor gene polymorphisms

In the last years, follice-stimulating hormone (FSH) receptor (FSHR) gene polymorphisms have been studied as potential risk factors for spermatogenetic failure. In this study, we have evaluated the response of FSH treatment in terms of sperm production on the basis of Ala307Thr-Asn680Ser polymorphisms in the FSHR gene in a group of oligozoospermic subjects with hypospermatogenesis and normal FSH levels. Patients were randomized into two groups: 70 treated with recombinant FSH (150 IU thrice per week for 3months) and 35 without treatment. After 3months of treatment, we observed significant increase in total sperm count, sperm concentration, forward motility, percentage of normal morphology forms and total motile sperm. When 70 treated subjects were subdivided based on FSHR genotype, only subjects with at least one serine in position 680 showed a statistically significant increase in these sperm parameters, whereas subjects with homozygote Thr307-Asn680 showed no difference in any seminal parameters evaluated. Non-treated subjects showed no differences in any parameter evaluated. This study suggests that the analysis of this gene represents a valid pharmacogenetic approach to the treatment of male infertility, confirming also the importance of strict criteria for the selection of patients to be treated with FSH.

Heat shock protein and heat shock factor expression in sperm: relation to oligozoospermia and varicocele.

PURPOSE Varicocele may be associated with normozoospermia or oligozoospermia. Much controversy still exists regarding the diagnosis, management and pathophysiology of spermatogenesis alterations associated with varicocele. The increased temperature induced by varicocele and stress in general may activate heat shock proteins and heat shock factors with a protective function in cells. We analyzed the expression of 5 heat shock proteins and heat shock factors in the sperm of men with normozoospermia and oligozoospermia with or without varicocele. MATERIALS AND METHODS We performed a prospective study between June 2008 and February 2009 at an academic clinic in 117 consecutive patients with varicocele and 68 controls without varicocele. Four groups were based on the presence/absence of varicocele and normozoospermia/oligozoospermia. Subjects were studied by history, physical examination, scrotal Doppler ultrasound, semen analysis, reproductive hormone plasma levels and quantitative real-time polymerase chain reaction in RNA extracted from ejaculated sperm to analyze HSP90, HSPA4, HSF1, HSF2 and HSFY expression. RESULTS Increased HSPA4, HSF1 and HSF2 were observed in the sperm of men with varicocele and in those with oligozoospermia. Levels were maximum when the 2 conditions were present. Increased HSP90 was observed in oligozoospermia cases independent of varicocele. HSFY was up-regulated only in patients with varicocele, especially those with normozoospermia. CONCLUSIONS To our knowledge we describe for the first time the expression of different heat shock proteins and heat shock factors in ejaculated sperm. While some of these proteins are up-regulated in men with oligozoospermia and varicocele, HSFY is up-regulated only in the presence of varicocele and especially in men with normozoospermia. This suggests that it may be a molecular marker of an adequate or inadequate response to the damaging effect of varicocele on spermatogenesis.

Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart.

Erectile function is a haemodynamic phenomenon depending on the integrity of neurological, vascular, endocrinological, tissue (corpora cavernosa), psychological and relational factors; changes in any one of these components may lead to erectile dysfunction (ED). ED and its comorbid conditions share common risk factors such as endothelial dysfunction, atherosclerosis and metabolic and hormonal abnormalities. Furthermore, although cross-sectional studies have shown a clear age-dependent association between ED, diabetes mellitus, hypertension, metabolic syndrome (MetS) and cardiovascular diseases, longitudinal evidence has recently emphasized that ED could be an early marker of these conditions. Recently, the European Association of Urology and American Urology Association provided consensus guidelines for the management of ED patients. However, the metabolic aspect of ED is rather neglected or not sufficiently treated. In this study, more emphasis will be placed on the presence of ED comorbid metabolic factors. The primary and secondary goals of therapy, according to current guidelines and to prevent their clinical evolution, will also be provided. We review the concepts of metabolic diseases related to ED and their treatment. Criteria for the diagnosis and treatment of hypogonadism, metabolic and vascular disease related to ED were analysed. ED can mark the starting point for the evaluation and prevention of significant severe diseases (such as diabetes, MetS, dyslipidaemia, arteriosclerosis, hypertension, ischaemic cardiopathy, neuropathy, etc.) hitherto unknown by the patients. Most widely used criteria for the diagnosis and treatment of these diseases were reported. We suggest a clinical approach which allows the identification of metabolic and others systemic pathologies contributing to the development of ED. This approach may constitute an improvement in disease prognosis and either induce a spontaneous reduction of ED or facilitate its specific therapy.

Cavernous artery intima-media thickness: a new parameter in the diagnosis of vascular erectile dysfunction.

INTRODUCTION A precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone. AIM We performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis. METHODS A total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study. MAIN OUTCOME MEASURES All subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Delta-cavernous calliper]). RESULTS Cavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT. CONCLUSIONS An increased cavernous IMT (>or=0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase.

Erectile dysfunction: symptom or disease?

Erectile dysfunction (ED) has been defined by the National Institute of Health (NIH) as the inability to achieve and/or to maintain an erection for a sufficiently long period of time so as to permit satisfactory sexual intercourse. ED affects millions of men throughout the world and could have a negative influence on the individual’s well-being as well as on the quality of life of affected subjects. Discordant data have been reported on ED epidemiology with prevalence ranging from 12% to 52%, probably depending on the different criteria utilized in the different studies for patient selection. ED is a symptom, sometimes the first, of different pathological conditions. In 15.7% of 45-yr-old patients with vascular ED a dynamic ergometric test has shown electrocardiographic alterations in the absence of any cardiac symptom. In 15% of the patients with ED, high fasting glucose plasma levels are discovered for the first time and in patients with ED and normal fasting glucose plasma levels the prevalence of undiagnosed diabetes mellitus is 12.1% after an oral glucose tolerance test (OGTT). The different risk factors are often additive in the possible development of systemic vasculopathy, neuropathy and ED. ED, underestimated in clinical practice due to archaic prejudice which hinders the patient in spontaneously revealing the problem and the physicians in investigating it, can mark the point where evaluation and prevention of important diseases (such as diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patients, can begin. The physicians’ cultural baggage must include the ability to identify the pathology that can determine ED and the ability to program a specific diagnostic workup. In this paper the different specialists involved in ED diagnosis agreed that a clinical approach which allows the identification of systemic pathologies contributing to the development of ED constitutes an improvement in disease prognosis and may either induce a spontaneous reduction of ED or facilitate its specific treatment.