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Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

Supplementary Table 1 from Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for In vitro and In vivo Activity

Supplementary Table 2 from Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for In vitro and In vivo Activity

Exposure to artificial light at night (ALAN) has been associated with disruption of the circadian system, which has been pointed out to have detrimental effects on health. Exposure to outdoor ALAN is very frequent in industrialised countries due to nocturnal light pollution and the relevant involvement of the total workforce in shift work and night work. Ecological and epidemiologic studies highlight the association between exposure to ALAN and several diseases, mainly obesity and cancer. More recently, also indoor ALAN exposure has been investigated. Among several multifactorial mechanisms linking ALAN exposure and health risks, suppression of melatonin secretion plays a pivotal role leading to alterations in circadian rhythm patterns, that are detrimental in terms of appetite regulation, and dysfunctions in metabolic signalling and cell growth in cancer. In addition, gut dysbiosis, inflammation, hypovitaminosis D, imbalance in cytokine secretion and levels are responsible for the multiple relationship linking circadian dysregulation due to ALAN exposure and obesity, and cancer. Therefore, the current manuscript summarises human and basic studies pointing out the impact of ALAN exposure on health, mostly focusing on obesity and cancer. Based on extant evidence, prevention strategies for obesity and cancer should be prompted, targeting exposure to ALAN. (C) 2022 Published by Elsevier Ltd.

Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year’s different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches.

Context We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions. Subjects and Methods Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded. Results Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein. Conclusions VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.

Summary Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions.

Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p &lt, 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.

Le diete chetogeniche, fortemente ipocaloriche e normoproteiche, consentono un’importante riduzione di peso e massa grassa a fronte di un risparmio del tessuto muscolare nei pazienti affetti da sovrappeso e obesita. Il rapido risultato ottenuto riducendo la sensazione di fame migliora la spinta motivazionale al trattamento. La loro prescrizione, anche tramite pasti sostitutivi, garantisce buoni esiti sulle comorbidita, proponendosi come valida opzione nell’ambito dei protocolli riabilitativi multidisciplinari.

Insulin resistance is the most important underlying cause of obesity and type 2 Diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits, widely known for their antioxidant properties, have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety, compliance and efficacy of mangosteen on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. 22 patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (HOmeostatic Model Assessment-Insulin Resistance, HOMA-IR -53.22% vs -15.23%, p=.0037), and a trend decrease in inflammation markers serum levels, together with trend greater weight loss and trend increased HDL levels. No side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible role of mangosteen in the treatment of obesity, insulin resistance and inflammation.

There is a widely acknowledged association between insulin resistance and obesity/type 2 diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits—known for their antioxidant properties—have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety and efficacy of treatment with mangosteen extract on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. Twenty-two patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (homeostatic model assessment-insulin resistance, HOMA-IR −53.22% vs. −15.23%, p = 0.004), and no side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible supplementary role of mangosteen extracts in the treatment of obesity, insulin resistance, and inflammation.

In the last century, both human life expectancy and maximum life span potential increased [1]. The analysis of North European mortality curves suggests that a relevant role for this phenomenon was played by the reduction of lifetime pathogen burden [2]. Whatever was the real cause, at the end of 1900, the improved hygienic conditions, the proper diet, the better health condition, and the decreased infant mortality elevated life expectation up to 80 years, with a consequent raise in elderly population of industrialized countries. In the society, the public perception of advanced aging involves the inability to survive alone due to chronic diseases and the combined loss of mobility, sensory functions, and cognition [3]. Age-related diseases, such as cardiovascular diseases, osteoporosis, cancer and neurodegenerative disorders, represent the major cause of morbidity and mortality in Western countries, with an exponential growth of health costs linked to increased size of elderly. For example, Alzheimer’s disease (AD) is the fifth leading cause of death in Americans aged 65 and older and deaths attributable to AD have been rising dramatically in the last decade (47 % increase between 2000 and 2006) [4]. With the increasingly aging population of the United States, the number of AD patients is predicted to reach 14 million in 2050, with an expected incidence of AD nearly to a million people per year and similar considerations apply worldwide [5]. Similar trends follow main age-related chronic diseases. This will pose an immense economic and personal burden on the actual and future generations, creating a critical emergency for effective therapeutic and preventive interventions. However, there is a judge difference among people that ages: There are people at the age of 60 years old that have extensive cognitive difficulties and chronic diseases and other that at 90 years old are still in good mental and physical condition. Avoiding age-related disease until late in life is key to “successful” aging. It is possible to transform in reality the constant dream of humankind: to stop, postpone, and/or reverse the aging process? During the last years, an increasing number of scientific meetings, articles, and books have been devoted to antiaging strategies and therapies. This topic is very popular among the general public, whose imagery has been fascinated by all possible tools and tricks to retard aging, thus approaching immortality, but it is also full of misleading, simplistic, or wrong ideas. In almost all instances, claims of drugs, health supplements, and other types of intervention are not based on any evidence supported by sound scientific knowledge. Of course, other approaches, including intervention in telomere shortening, cell cycle control, interfering with the oncogene/anti-oncogene homeostatic balance, etc. are being studied as possible “antiaging” manipulations. Although solid data suggesting increased survival time in vitro or life span expansion in experimental animals in vivo has been reported in some of these instances, these interventions are still far from being applicable in the complex human situation, and must therefore await further scrutiny, particularly with regard to still unknown side effects [6]. Thus, in the present chapter, antiaging strategies aimed not to rejuvenate, but to slow aging and to delay or avoid the onset of age-related diseases are discussed, allowing to substantially slow down the aging process, extending people’s productive, youthful lives. In particular, it will briefly focus on the most promising approaches proposed to obtain a healthy longevity: nutritional strategies, physical activity, and hormone therapy. Furthermore in this context, some specific skin antiaging aspects will be also discussed. Skin aging, in fact, is particularly important because of its social impact, but also represents an ideal model organ for investigating the aging process.

Aims: Osteogenesis imperfecta (OI) is a rare inherited disorder causing low bone density and increased fragility. Bisphosphonates (BP) are a treatment of choice for OI. Few studies have investigated the long-term effects of BP in OI patients. Thus, aim of our study was to follow up adults affected by OI to evaluate changes in metabolic, clinical situation and safety of long-term neridronic acid therapy, BP authorized for OI treatment. Study design: Longitudinal observational study. Place and duration of the Study: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition. Year: 2004 - October 2010. Methodology: 68 patients underwent clinical examination, laboratory endocrine/ metabolic, pro-inflammatory cytokines screening, ECG at baseline and every 3 months and bone mineral density evaluation, by DEXA, once a year. Results: Skeletal evaluation showed a significant increase of BMD through follow up. Patients were evaluated for metabolic and cardiovascular risk factors, which were unmodified by long-term therapy. Conclusion: Long-term neridronic acid treatment increases bone density, does not alter metabolic parameters indicating that this therapy can be considered safe and a valid therapeutic option for OI patients.

The application of digital pulse amplitude by fingertip peripheral arterial tonometry (PAT) device in patients with erectile dysfunction (ED) has never been performed. We investigated the diagnostic value of reactive hyperaemia (RH) and augmentation index (AI) as evaluated using PAT in men with ED of any origin. A total of 40 patients underwent diagnostic investigation for ED, including dynamic penile duplex ultrasound (PDU) and PAT device. Moreover, 30 patients without ED served as controls. According to PDU cutoff at 35 cm/sec, patients were divided into vascular (n = 30) and nonvascular (n = 10) ED aetiology. Moreover, controls with (n = 10) or without (n = 20) vascular risk factors (VRFs) were studied in a separate analysis. Average RH-PAT was not different in men with or without ED (P = 0.56) independently of VRFs. The AI was higher in men with ED compared with the controls (P < 0.0001) as well as when controlled for the presence or absence of VRFs (P < 0.0001). An inverse relationship between AI and PSV was also found (r² = -0.72, P < 0.0001). In conclusion, an increased AI but not an impaired RH-PAT is present in men with vascular ED independently of VRFs and may represent an early detection of vascular impairment that may precede endothelial dysfunction in populations at low risk for developing vascular ED.

Penile erection is a vascular event that requires an intact endothelium to occur. A dysfunctional endothelium is an early marker for the development of atherosclerotic changes and can also contribute to the occurrence of acute cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction (ED) is intimately linked through decreased expression and activation of endothelial nitric oxide (NO) synthase, and the subsequent blunted physiological actions of NO naturally occurring with aging. It is now well-understood that ED is a symptom of underlying disease rather than a disease itself; for this reason in the near future both general practitioners, internal medicine practitioners and many specialists will have to interplay with sexual medicine. Aging in the man is also associated with several changes in arterial structure and function, part of them related to the decline of circulating levels of steroids, that is, testosterone and estradiol. These changes may be responsible, in part, for the lack of efficacy of ED treatments. The recent discovery that chronic administration of phosphodiesterase type 5 inhibitors may improve erectile and endothelial responsiveness of men previously non-responsive to on-demand regimes, and the knowledge that testosterone is one of the main modulators of the expression of penile phosphodiesterase type 5 isoenzyme, opens a new scenario in the treatment of men with ED and co-morbidities. The aim of this review is to discuss the pathophysiology of endothelial dysfunction and its relationship with ED in the aging male, and to suggest possible strategies to improve arterial function with regard to sexual dysfunctions.

Osteogenesis imperfecta (OI) is a rare inherited connective disorder causing increased bone fragility and low bone mass. OI includes severe bone fragility, impaired dentinogenesis, with less common alterations in the joints, blood vessels, heart valves, skin. Interestingly, description of left ventricular rupture, aortic dissection and heart valves incompetence has been previously described. Death may occur in OI patients for cardiac disease in asyntomatic subjects. Aim of our study has been to evaluate the presence of potential subclinical cardiac disorders and to characterize cardiac functional parameters by echocardiography in adults with OI in absence of cardiac symptoms. Forty patients (21 females and 19 males) affected by type I, III, IV OI and 40 control subjects (20 females and 20 males) were evaluated in the study. Patients and controls underwent clinical examination, screening for endocrine and metabolic disorders, 12-lead electrocardiogram and echocardiogram. In particular, all subjects were evaluated by two-dimensional echocardiography with continuous- and pulse-wave Doppler. Patients and controls belonged to NYHA class I and no significant electrocardiographic alteration was documented in both groups. Thirty-eight patients (95%) showed valvular regurgitation compared to one control subject (2.5%; P0.001). As regards the diastolic function parameters, in OI patients E wave velocity was reduced by 23% (95% CI: 9% to 29%; P0.001), E/A ratio was reduced by 17% (95% CI: 15% to 26%; P0.001) while isovolumetric relaxation time (IRT) was increased by 47% (95% CI: 26% to 53%; P0.001) and E wave deceleration time (DT) was increased by 18% (95% CI: 13% to 26%; P0.001) compared to controls. In conclusion, our data indicate that adult patients affected by OI have an altered diastolic function in absence of other metabolic alterations. These diastolic echocardiographic parameters might worsen over time, especially if other cardiovascular risk factors (e.g., smoking, hypertension, metabolic and endocrine alterations) are not carefully checked, monitored and treated. In the context of a multidisciplinary evaluation of OI patients, our data suggest that a careful cardiological evaluation of these patients is indicated beside skeletal evaluation and therapeutical skeletal options.

Background: Cross-sex hormone treatment in male-to-female (M2F) transsexuals appears reasonably safe. Little is known about its long-term use. The aim of our study was to evaluate the effect of long-term high dose estrogens, plus the antiandrogen cyproterone acetate, on bone composition and on biochemical/hormonal parameters in M2F transsexuals. Methods: A retrospective analysis was performed on 45 young M2Fs (mean age 39.5 years; body mass index (BMI) = 22) receiving estrogens (previously 100 μg ethinyl estradiol, now 2–4 mg oral estradiol valerate/day or 100 μg transdermal estradiol/day) plus the antiandrogen cyproterone acetate 100 mg/day. Data were retrieved from 20 subjects after reassignment surgery (mean hormonal treatment duration 15.6 years). A complete hormonal and biochemical assessment, as well as bone biochemical markers (parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase and plasma pyridinoline crosslinks), were evaluated. Bone mineral density (BMD) was measured us...

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), mono-ortho and non-ortho polychlorinated biphenyls (dioxin-like PCBs) were determined in samples of human fat tissue from nine Italian obese patients. The toxicity equivalent (TEQ) values ranged from 9 to 25 pg TEQ g−1 lipid (WHO-TEF values, 2005 [Van den Berg, M., Birnbaum, L.S., Denison, M., De Vito, M., Farland, W., Feeley, M., Fiedler, H., Hakansson, H., Hanberg, A., Haws, L., Rose, M., Safe, S., Schrenk, D., Tohyama, C., Tritscher, A., Tuomisto, J., Tysklind, M., Walker, N., Peterson, R.E., 2006. The 2005 World Health Organization reevaluation of human and mammalian Toxic Equivalency Factors for dioxins and dioxin-like compounds. Toxicol. Sci. 93, 223–241]), the contribution of dioxin-like PCBs was more than 30% of the total TEQ values. The obese body burdens varied from 6 to 11 ng TEQ kg−1 body weight (BW), exceeding the estimated steady-state body burden 5 ng TEQ kg−1 BW, based on lipid adjusted serum concentrations from several populations in the mid-1990s, calculated in the risk assessment US EPA document.

Objective Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). Methods In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. Results After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 ± 0.5 to 12.5 ± 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. Conclusions In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition. Diabet. Med. 25, 37–44 (2008)

Cancer has a complex etiology with multiple risk factors that involve the interplay between genetic and environmental influences. There is compelling evidence that dietary plant foods appear to be protective against certain type of cancers. Among a number of mechanistic hypotheses, diet-derived antioxidants have been proposed to contribute to explain these findings. However, contrasting results from intervention trials have raised strong concerns about the influence of antioxidants on human health. A vulnerable point of the research on antioxidants is the lack of information on the effect of the whole array of dietary antioxidants in cancer prevention because so far mainly single molecules have been investigated. Total antioxidant capacity (TAC) considers the single antioxidant activity as well as the synergistic interactions of the redox molecules present in complex matrixes, giving an insight into the assessment of the non-enzymatic antioxidant network. This article will outline the state of art of the research on TAC and cancer, describing the plasma non-enzymatic antioxidant network and its association with diet. The feasibility of TAC assessment as an innovative tool for investigating the association between dietary antioxidants, oxidative stress, and cancer will be also discussed.

Men with erectile dysfunction (ED) frequently have a disproportionate burden of comorbid vascular disorders including atherosclerotic disease. We investigated whether scheduled tadalafil is better than on-demand (OD) in improving endothelium-dependent vasodilatation of cavernous arteries in men with ED and whether this effect is also exerted on markers of endothelial function. We did an open-label, randomized, crossover study including 20 male outclinic patients aged 18 years or older (mean age 54 years) who had at least a 3-month history of ED of any severity or etiology. Tadalafil (20 mg) on alternate days (ADs) or OD was administered for 4 weeks. Primary end points were variations of basal inflow (peak systolic velocity (PSV)) and flow-mediated dilatation (FMD) of cavernous arteries compared with baseline at penile Duplex ultrasound. Secondary end points were variations of Q13-SIEDY scores regarding morning erections and of markers of endothelial function, that is, vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule, endothelin-1 (ET-1), insulin and C-reactive protein (CRP). PSVs and FMD were higher after AD treatment when compared with OD and baseline, respectively (P=0.0001), and improvements were maintained from 2 weeks after discontinuation (P

Introduction. It has been reported that lack of sexual activity due to erectile dysfunction (ED) may be associated with testosterone (T) decline. Aim. To investigate whether the known changes in sex hormones associated with resumption of sexual activity are sustained in the long term. Main Outcome Measures. Primary endpoints were variations from baseline of steroid hormones: total T, free T (f T), and estradiol (E). Secondary endpoints were variations of erectile function domain scores at International Index of Erectile Function-5 (IIEF-5). Methods. In an open-label fashion, 20 patients (mean age 54.8 ± 8.4 years) received tadalafil 10-20 mg on demand for 12 months. Exclusion criteria were those reported for phosphodiesterase inhibitors, including hypogonadism and hyperprolactinemia. Results. Tadalafil assumption was safe and well tolerated (overall adverse effects in 15% of patients) and none discontinued medication. A significant decrease in E levels occurred at the end of the study (from 19.9 ± 9.6 to 16.6 ± 8.1 ng/dL, P = 0.042 vs. baseline), with parallel increase in the T:E ratio (26.3 ± 15.3 to 32.6 ± 17.7, P = 0.05), whereas no changes in T and f T serum levels were observed, respectively (411.4 ± 131.4 to 434.2 ± 177.1 ng/dL and 47.7 ± 15.3 to 49.9 ± 19.1 pmol/L, not significant). Interestingly, nonparametric subgroup analysis for related samples revealed that E decrease was detectable only in lean (N = 14) but not in obese (N = 6, body mass index > 27.5 kg/m 2 ) subjects (17.8 ± 10.1 vs. 13.5 ± 6.8, P < 0.05). A net increase in IIEF-5 scores was observed at the endpoint (13.7 ± 5.9 vs. 25.7 ± 2.9, P < 0.0001). Conclusions. Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil might have a role in the regulation of erectile function. Greco EA, Pili M, Bruzziches R, Corona G, Spera G, and Aversa A. Testosterone:estradiol ratio changes associated with long-term tadalafil administration: A pilot study. J Sex Med 2006;3:716-722.

Introduction Systemic sclerosis is a connective tissue disease characterized by Raynaud's phenomenon, degenerative changes and vascular lesions in the presence of thickened, sclerotic skin lesions determined by cellular proliferation, and excess of extracellular matrix production. The role of ultrasound in the investigation of penile pathology is well established as vasculogenic impotence accounts for more than 30% out of overall causes. Aim In this article, we report for the first time the extent of penile vascular damage in a series of 15 sclerodermic patients (mean age 47 ± 12.5 SD) under current treatment for their disease irrespective of their sexual dysfunction complaints. Methods After disease classification (mean duration of disease 7.2 ± 5.1 years), all patients were interviewed about the presence or absence of erectile dysfunction (ED) by using the Sexual Health Inventory for Men (SHIM) questionnaire, and then blood flow velocity in the cavernous artery following standardized pharmacostimulation was determined with Duplex ultrasonography along with the intima media thickness (IMT) of the common carotid artery, a valid index for atherosclerosis. Results Mean SHIM scores revealed the presence of moderate‐to‐severe ED (mean 13.3 ± 6.3). Interestingly, in all patients diffuse hyperechoic “spots” inside the corpora cavernosa along with thickening of the tunica albuginea were found. Severely impaired mean peak systolic velocities (20.2 ± 5.5 cm/second) in the presence of mild venous leakage as expressed by mean end diastolic velocities (4.6 ± 2.9 cm/second) were found along with normal IMT (0.065 ± 0.010 cm) and acceleration time (92.3 ± 32.7 cm/second). Conclusion Penile fibrosis almost invariably occurs in sclerodermic patients and this determines incomplete penile arterial and smooth muscle cell relaxation and ED despite the absence of indirect signs of early atherosclerosis, that is, abnormal IMT and acceleration time. Aversa A, Proietti M, Bruzziches R, Salsano F, and Spera G. The penile vasculature in systemic sclerosis: a Duplex ultrasound study. J Sex Med 2006;3:554–558.

Background: The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery. Methods: We prospectively investigated the effects of the bilio-intestinal bypass (BI-bypass) with a wide cholecysto-jejunal anastomosis and of adjustable gastric banding (AGB) on blood lipid concentrations in obese patients. To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass, daily fecal sterol excretion was measured by gas-liquid chromatography (GLC). Results: At 1 year after BI-bypass compared to baseline, the hypercholesterolemic (n=18) and the normocholesterolemic (n=19) patients significantly reduced total (−38% and −27%, respectively), LDL (−47% and −24%, respectively) and HDL (−11% and −13%, respectively) cholesterol and total / HDL cholesterol ratio (−25% and −13%, respectively). At 1 year after AGB, the total / HDL cholesterol ratio was significantly decreased (−11%) compared to baseline in hypercholesterolemic (n=12) but not in normocholesterolemic (n=6) patients, while total and LDL cholesterol were not affected in both groups. At 3 years after BI-bypass compared to baseline, the hypercholesterolemic (n=9) and the normocholesterolemic (n=11) patients significantly reduced total (−43% and −28%, respectively) and LDL (−53% and −29%, respectively) cholesterol and total / HDL cholesterol ratio (−38% and −21%, respectively). The BI-bypass induced a significant (P

The platelet-derived growth factor (PDGF) family of ligands and receptors play a pivotal role in the development of various organs. The critical importance of the PDGF-mediated signaling during embryonic development and adult physiology of the kidney and the common mesonephric origin of the epididymis and kidney prompted us to investigate the immunohistochemical localization of PDGF A- and B-chain and PDGF receptor (PDGFR) alpha- and beta-subunit in rat and mouse epididymis, the expression profiles of the corresponding mRNAs, and the consequences of a loss-of-function mutation at the PDGF-A, PDGF-B, and PDGFR-beta loci on mouse epididymis phenotypic appearance. Prenatally, PDGF-A and PDGFR-alpha immunohistochemical staining was seen in both species, whereas PDGF-B and PDGFR-beta were absent. The cellular localization of PDGF-A within the epithelium and the alpha-receptor in the mesenchyme in either mouse or rat before birth suggests that the PDGF-A/PDGFR-alpha system might be involved in the epididymal epithelial-mesenchymal interaction during the fetal period of life. Postnatally, PDGF A- and B-ligand and PDGFR alpha- and beta-subunit were confined in the epithelium. The identity of PDGF and PDGFR proteins were further confirmed by immunoblotting. In line with the immunohistochemical studies, PDGF-A and PDGFR-alpha mRNAs were seen by reverse transcription-polymerase chain reaction in rat and mouse tissue before birth, whereas PDGF-B and PDGFR-beta were almost not detectable. During the first days of life, PDGF-B and PDGFR-beta genes started to appear, and the overall trend in mRNA expression throughout postnatal development showed that the transcripts levels for PDGF-A, PDGF-B, PDGFR-beta, and PDGFR-alpha were constant with the only exception of a progressive decrease of PDGFR-alpha in adult rats. The PDGF-A null mutation strongly influenced the epididymal phenotype starting from puberty; only fetal PDGF-B and PDGFR-beta -/- mice were available, and no differences were seen in the epididymis of these animals, compared with wild-type littermates. Taken together, these data indicate that the PDGF system is highly expressed in the epididymis and suggest that PDGF could be involved in the maintenance of morphological structure and functional control of this organ.

Summary objectives We have recently shown that, in men with erectile dysfunction (ED), free testosterone (FT) directly correlates with penile arterial inflow. This led us to further investigate the effect(s) of androgen administration on cavernous arteries in patients failing sildenafil treatment. design Prospective randomized placebo-controlled pilot study. patients Twenty patients with arteriogenic ED as evaluated by dynamic colour duplex ultrasound (D-CDU) studies, normal sexual desire but testosterone (T) and FT in the lower quartile of normal range (low-normal), not responding to sildenafil treatment (100 mg) on six consecutive attempts. measurements All patients had D-CDU, hormonal [LH, prostate-specific antigen (PSA), total and free testosterone, sex hormone-binding protein (SHBG), oestradiol], biochemical [haematocrit, low-density lipoprotein (LDL) and HDL cholesterol, triglycerides], and sexual evaluations [International Index of Erectile Function (IIEF)] before and after 1 month of therapy with transdermal testosterone (5 mg/day, n = 10) or placebo along with sildenafil treatment on demand. Measurement of flow parameters by D-CDU on cavernous arteries was the primary endpoint of the study. Improvement of erectile function was assessed using the IIEF questionnaire and the Global Assessment Question (GAQ). results One month treatment with transdermal testosterone led to a significant increase in T and FT levels (23·7 ± 3·3 SD vs. 12·8 ± 2·1 nmol/l and 473 ± 40·2 vs. 260 ± 18·1 pmol/l, P

Testicular development is controlled by a complex hierarchy of gene regulatory proteins, growth factors, cell adhesion molecules, signaling molecules and hormones that interact, often acting within short time windows, via reciprocal control relationships. The identification in the testis of platelet-derived growth factor (PDGF), a key regulator of connective tissue cells in embryogenesis and pathogenesis, has focused attention on the role of this growth factor in testicular pathophysiology. This review summarizes recent advances in the study of the actions of PDGF in the male gonad, and attempts to incorporate complex in vitro and in vivo experimental data into a model that might clarify the role played by PDGF in the mammalian testis.

To investigate safety, compliance, and efficacy, on weight loss and cardiovascular risk factors of a multi- phasic dietary intervention based on meal replacements, including a period of very low calorie diet (VLCD) in a population of obese patients. Anthropometric parameters, blood tests (including insulin), dual-energy-X-ray absorp- tiometry (DXA), and questionnaires for the assessment of safety and compliance before and after (phase I) a 30-day VLCD, 700 kcal/day, normoproteic, 50 g/day carbohy- drate, four meal replacements; (phase II) a 30-day low calorie diet (LCD), 820 kcal/day, three meal replacements plus a protein plate; (phase III) 60-day LCD, 1,100 kcal/ day, two meal replacements plus two protein plates and reintroduction of small amounts of carbohydrates; (phase IV) 60-day hypocaloric balanced diet (HBD), 1,200 kcal/ day, one meal replacement, two protein plates and the reintroduction of carbohydrates. 24 patients (17 females, 7 males, mean BMI 33.8 ± 3.2 kg/m 2 , mean age 35.1 ± 10.2 years) completed the study. The average weight loss was 15.4 ± 6.7 %, with a significant reduction of fat mass (from 32.8 ± 4.7 to 26.1 ± 6.3 % p \ 0.05) and a relative increase of lean mass (from 61.9 ± 4.8 to 67.1 ± 5.9 % p \ 0.05). An improvement of metabolic parameters and no variations of the liver and kidney functions were found. A high safety profile and an excel- lent dietary compliance were seen. The VLCD dietary program and the replacement dietary system described here is an effective, safe, and well-tolerated treatment for weight control.

Raloxifene (RAL), a selective estrogen receptor modulator, is indicated for the prevention and treatment of postmenopausal osteoporosis. RAL, by decreasing bone turnover, prevents bone loss and microarchitecture damage, reducing the incidence of osteoporotic fractures. Our previous in vitro data demonstrated that RAL modulates osteoclast activity by, at least in part, an IL-6- and TNF-alpha-dependent mechanism. In this study we evaluated the effects of RAL treatment (60 mg/d) on circulating levels of these cytokines in 14 postmenopausal women with osteoporosis. Lumbar bone density (determined by dual energy x-ray absorptiometry) and IL-6 and TNF-alpha levels were measured before and after 6 and 24 months of therapy. After 24 months, RAL increased bone density. IL-6 and TNF-alpha expression, elevated before treatment, significantly decreased (50% and 30%, respectively) after 6 months. This effect was sustained up to the end of the treatment (75% and 35%, respectively). Thus, our data show that RAL can modulate circulating levels of cytokines involved in osteoclastogenesis and bone resorption, suggesting that modulation of soluble factors could play a pivotal role in the mechanisms of the osteoprotective effect of RAL.

Summary Pachydermoperiostosis is a rare osteo-cutaneous disease characterized by hypertrophy of bones and surrounding soft tissues. The cutaneous manifestations include coarsening of facial features, cutisverticis gyrata, digital clubbing, hyperhidrosis and scborrhoea. The pathogenetic mechanism of the disease is still debated, and proposed aetiological factors include genetic influences, anomalies in fibroblast activity, or alteration in peripheral blood flow. We studied a patient with the incomplete form of Pachydermoperiostosis. assessing epidermal growth factor receptor (EGF-R) and sex hormone steroid receptors (SR) in the affected skin, and also evaluating the urinary excretion of EGF. The results showed high levels of nuclear steroid receptors, increased cytosolic oestrogen receptors, and no detectable progesterone and androgen cytosolic receptors. EGF-R was also undetectable, and the urinary excretion of EGF was elevated. These findings suggest that the increased tissue sensitivity to circulating sex-steroids could induce enhanced tissue EGF/transforming growth factor α (TGF-α) production and utilization. The SR-EGF-R system could therefore be involved in determining hypertrophy of the affected tissues.

Stefania Mariani,1 Daniela Fiore,1 Laura Varone,2 Sabrina Basciani,1 Agnese Persichetti,1 Mikiko Watanabe,1 Maurizio Saponara,3 Giovanni Spera,1 Costanzo Moretti,4 Lucio Gnessi11Department of Experimental Medicine, Section of Medical Physiopathology and Endocrinology, Sapienza University of Rome, Italy; 2Department of Environmental Biology, Sapienza University of Rome, Italy; 3Department of Otolaryngology, Audiology and Phonation, Sapienza University of Rome, Italy; 4Division of Endocrinology, Department of System Medicine, Section of Reproductive Endocrinology University of TorVergata, Fatebenefratelli Hospital "San Giovanni Calibita" Rome, ItalyContext: Obesity and its co-morbidities may adversely affect bone mineral density (BMD). Obstructive sleep apnea (OSA) is a major complication of obesity. To date, the effects of OSA on BMD in obese patients have been poorly studied.Objective: To examine whether the severity of OSA independently correlates with BMD in obese patients.Methods: One hundred and fifteen obese subjects with OSA (Apnea/Hypopnea Index [AHI] ≥5 events per hour) were included in the study. BMD was measured at lumbar spine, total hip, and femoral neck by dual energy X-ray absorptiometry. Body mass index, lean mass, and representative measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL-cholesterol, triglycerides) and inflammation (ESR, CRP, fibrinogen) were also evaluated.Results: BMD did not differ among obese individuals regardless of OSA severity. Correlation coefficient analysis for all the covariates showed a lack of association between AHI and BMD that was strongly influenced by age and weight.Conclusion: Our study does not support an independent association between AHI and BMD in obese patients. Controlled studies involving a greater number of patients are warranted.Keywords: obesity, polysomnography, metabolic syndrome

Objective To report the effect of long-term treatment with the tyrosine kinase inhibitor imatinib started before the onset of puberty on semen parameters, bone mineral density, and hormone values. Design Case report. Setting University hospital. Patient(s) An 18-year-old man given treatment with imatinib for chronic myeloid leukemia. Intervention(s) Clinical, biochemical and dual-energy X-ray absorptiometry evaluations. Main Outcome Measure(s) Semen analysis, serum levels of gonadotropins, inhibin-B, and testosterone, bone mineral density, markers of skeletal homeostasis. Result(s) Semen analyses showed severe oligozoospermia after long-term administration of imatinib started before puberty. The inhibin-B/FSH ratio was reduced. A low bone mineral density for chronologic age was observed. Conclusion(s) This case study documents the potential risk of an impairment of semen parameters in patients undergoing a treatment with tyrosine kinase inhibitors before the complete maturation of the testis.

Human benign prostatic hyperplasia (BPH) samples were analyzed to evaluate the presence of immunoreactive epidermal growth factor (irEGF) and EGF receptor (EGFR). In all BPH samples examined both peptide and its receptor were present. Scatchard analysis of binding data of [125I]EGF showed two classes of binding sites with high and low affinity. Intratissular irEGF concentrations showed a significant inverse linear correlation with EGFR levels. Two groups of samples can be identified: the first showing high irEGF concentrations and low levels of EGF binding sites; the second low irEGF and high concentrations of EGFR. The simultaneous presence of EGF and its receptor in BPH samples indicates that this growth factor may act in an autocrine/paracrine manner in human prostatic tissue. The inverse relationship between EGF and the two sites of EGFR lead one to hypothesize that EGF itself could play a central role in determining receptor cell surface availability.

The response of purified rat testicular peritubular myoid cells (PMC) to platelet-derived growth factor (PDGF) was studied. Freshly isolated PMC were devoid of measurable amounts of PDGF-binding sites. However, after 1 day in culture in serum-free conditions, specific high affinity receptors were detected. The estimated binding sites per cell revealed that PMC express more receptors for PDGF-BB, followed by PDGF-AB and PDGF-AA. PDGF treatment of cultured PMC increased the cytosolic Ca2+ concentration, showing a rank order of potencies with PDGF-BB > PDGF-AB > PDGF-AA. PMC proliferation, as measured by direct cell counting, was also stimulated by all three PDGF isoforms, with the same order of potencies observed for the increase in intracellular Ca2+. This effect was inhibited by antibodies to PDGF. Moreover, PDGF treatment increased the release of type IV collagen and fibronectin, and induced the release of type V collagen and laminin. These results demonstrate that testicular PMC are induced to express functionally active PDGF receptors in response to cell culturing. These data suggest that PMC may be a target for PDGF and that PDGF-mediated effects in vivo are dependent on factors regulating the expression of the receptors. The role that PDGF may play in normal and pathological testicular processes is discussed.

Prolonged tadalafil administration in men with erectile dysfunction is associated with increased testosterone (T): estradiol (E(2)) ratio mainly related to reduction of E(2) levels.To investigate the presence of phosphodiesterase type 5 (PDE5) isoenzyme in primary human visceral adipocytes and whether different PDE5 inhibitors (PDE5i) could directly modulate aromatase (ARO) expression in differentiated human visceral adipocytes in culture.PDE5 mRNA and protein expression in primary human visceral adipocytes as well as mRNA and protein expression of ARO, with functional activity after selective PDE5 blockade by tadalafil and sildenafil.Purified primary human visceral pre-adipocytes were differentiated ex vivo and were exposed to tadalafil or sildenafil (1 µM) for different intervals of time (6-12-24-96 hours). ARO mRNA content and expression were measured by Western Blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. T and E(2) in supernatants were measured by ELISA also in the presence of letrozole.Differentiated adipocytes were found to express detectable levels of PDE5 transcripts. Acute exposure (6 hours) to both PDE5i tadalafil and sildenafil increased ARO mRNA expression by 4.7- and 2.8-fold, respectively (P0.001). ARO mRNA and protein levels were increased by the treatment with PDE5i in a time- and dose-dependent manner. Such effect was mimicked by 8-bromo-cGMP but was lost after 24 and 96 hours; differently, the PDE3B specific inhibitor milrinone (1 µM), displayed no effect. Accordingly, long-term exposure (24 and 96 hours) to PDE5i caused a significant increase in E(2) concentrations in the supernatant (1.7 and 2 fold, respectively; P0.001), with a parallel reduction of T (15% and 30%, respectively; P0.001). Such effect was reversed by the co-incubation with the specific ARO-inhibitor letrozole.Our results demonstrate that PDE5 is expressed in human visceral adipocytes and that acute exposure to PDE5i selectively stimulates ARO expression, which is related to a specific PDE5 blockade. We speculate that modulation of ARO activity by PDE5i could be one of the mechanisms responsible, at least in part, for the beneficial effects of PDE5i on endothelial and metabolic functions.

Normal development and function of the testis are controlled by endocrine and paracrine signaling pathways. Platelet-derived growth factors (PDGFs) are growth factors that mediate epithelial-mesenchymal interactions in various tissues during normal and abnormal processes such as embryo development, wound healing, tissue fibrosis, vascular disorders, and cancer. PDGFs and their receptors (PDGFRs) have emerged as key players in the regulation of embryonic and postnatal development of the male gonad. Cells that express PDGFs and PDGFRs are found in the testis of mammals, birds, and reptiles, and their distribution, regulation, and function vary across species. Testicular PDGFs and PDGFRs appear after the process of sex determination in animals that use either genetic sex determination or environmental sex determination. Sertoli cells are the main PDGF-producing cells during the entire period of prenatal and postnatal testis development. Fetal Leydig cells and their precursors, adult Leydig cells and their stem cell precursors, peritubular myoid cells, cells of the blood vessels, and gonocytes are the testicular cell types expressing PDGFRs. Genetically targeted deletions of PDGFs, PDGFRs, PDGFR target genes or pharmacological silencing of PDGF signaling produce profound damage on the target cells that, depending on the developmental period, are under direct or indirect control of PDGF. PDGF signaling may also serve diverse functions outside of the realm of testis development, including testicular tumors. In this review, we provide a framework of the current knowledge to clarify the useful information regarding how PDGFs function in individual cells of the testis.

Introduction. Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease. Aim. To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11 nmol/L or free T at or below 250 pmol/L). Methods. This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57 8) were randomized (4:1) to receive TU 1,000 mg (every 12 weeks) or placebo (PLB) gel (3-6 g/daily) for 24 months. Main Outcome Measures. Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP). Results. At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P < 0.001), CIMT (P < 0.0001), and hsCRP (P < 0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P < 0.0001) and 58% (P < 0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P < 0.0001), visceral fat mass (P < 0.0001), and improvement in HOMA-IR without changes in body mass index (BMI). Conclusions. TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events. Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, and Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle- aged men with late onset hypogonadism and metabolic syndrome: Results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med 2010;7:3495-3503.

SUMMARY Background: Obese individuals often present comorbidities while they appear protected against the development of osteoporosis. However, few and contradictory data are now available on skeletal modifications in obese patients. The aim of this study was to characterise bone mineral density (BMD) in overweight (BMI > 25 30) patients. Methods: We selected 398 patients (291 women, 107 men, age 44.1 + 14.2 years, BMI 35.8 + 5.9 kg ⁄m 2 ) who underwent clinical examination, blood tests and examination of body composition. Subjects with chronic conditions or taking medications interfering with bone metabolism, hormonal and nutritional status and recent weight loss were excluded. Results: Interestingly, 37% (n = 146) of this population showed a significantly lower than expected lumbar BMD: 33% (n = 98) of women showed a T-score )1.84 ± 0.71, and 45% (n = 48) of men showed a T-score )1.88 ± 0.64. When the population was divided into subgroups based on different BMI, it was noted that overweight (BMI > 25 30) was associated with a low bone mass, compatible with a diagnosis of osteoporosis. No differences were observed in hormones and lipid profiles among subgroups. Conclusions: Our results indicate that a subpopulation of obese patients has a significant low lumbar BMD than expected for age. Thus, a careful characterisation of skeletal metabolism might be useful in all obese individuals to avoid fragility fractures later in life. What’s known Women with high body mass index seem to be protected against osteoporosis. However, merging data on this issue are conflicting.

The prevalence of erectile dysfunction (ED) in men with systemic sclerosis (SSc) can be considered a manifestation of endothelium damage. Aim of the study is to investigate ED in SSc patients by color Doppler ultrasound examination and to correlate it with disease severity and digital vascular damage.In 20 males SSc patients blood flow velocity in the cavernous artery was determined with Duplex ultrasonography. Naifold videocapillaroscopy, Sexual Health Inventory for Men (SHIM) and Medsger Disease Severity Scale (DSS) were performed. Arteriogenic ED was defined by the presence of a reduced peak systolic velocity (PSVs), while diastolic velocity (EDV) and the resistive index (RI) were estimated to evaluate venocclusive dysfunction. SSc patients are classified by capillaroscopic pattern and vascular domain of DSS into two groups: low vascular damage (early or active capillaroscopic pattern and score of vascular domain of DSS≤2) and high vascular damage (late capillaroscopic pattern and score of vascular domain of DSS≥3).In all SSc patients a reduction of SHIM is present (mean 13.5±6.3). Patients with less vascular damage have a significantly (p0.001) higher score of SHIM than patients with greater vascular damage (19.2±2.4 vs 7.9±2.7). No significant difference (p0.5) between the two groups of vascular damage was found in PSVs. Venocclusive dysfunction was present only (p0.001) in the group with high vascular damage.We can assert that there is a relationship between SSc vascular digital damage and ED.

Obesity is an increasing health problem and surgery seems to be the only treatment effective in achieving weight loss without relapse. Among bariatric techniques, many differences exist in terms of weight loss and resolution of comorbidities. Up to now, there are no prospective studies comparing long-term effects of malabsorptive vs restrictive techniques. In this study, cardiometabolic risk factors and body composition changes after malabsorptive biliointestinal bypass (BIBP) and restrictive laparoscopic adjustable gastric banding (LAGB) were compared during a 4-year follow-up. Prospective, case–control and cohort study. In all, 80 obese subjects, matched for weight and age. Altogether, 40 patients underwent BIBP and 40 underwent LAGB. Weight, body composition, fasting and post-loading plasma glucose and insulin, homeostatic model assessment index (HOMA-I), lipid profile, blood pressure (BP), erythrocyte sedimentation rate and fibrinogen were monitored at baseline, 12 and 48 months. At 12 months after surgery, a significant reduction in body mass index, total fat mass (FM), trunk FM (trFM), trFM/legs FM (lFM) ratio (trFM/lFM), triglycerides, BP and inflammation markers was observed in both groups. BIBP patients showed a significant reduction in total cholesterol (Tot-C), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), whereas the LAGB group showed a significant increase of HDL-C. A further improvement of all the parameters evaluated was seen in the BIBP group at 48 months after surgery. Both bariatric procedures exerted positive effects on cardiometabolic risk factors and on weight loss in the population studied, but on the long-term period, HOMA-I, Tot-C/HDL-C ratio and body composition improvements were more evident after BIBP. We conclude that malabsorptive BIBP seems to be more effective than LAGB in treating visceral obesity and its metabolic complications

Systemic Sclerosis (SSc) is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED) because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ‘‘sclerodermic penis’’. Once-daily phosphodiesterase type-5 (PDE5) inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.