Chronic, long-term administration of Vardenafil improves endothelial function and corrects hypogonadism in patients with type 2 diabetes mellitus. A longitudinal, prospective, randomized, placebo-controlled, double blind, clinical trial

10.1530/endoabs.37.OC4.

Audio-based narratives for the trenches of World War I : intertwining stories, places and interaction for an evocative experience

We report in detail the co-design, setup and evaluation of a technological intervention for a complex outdoor heritage site: a World War I fortified camp and trenches located in the natural setting of the Italian Alps. Sound was used as the only means of content delivery as it was considered particularly effective in engaging visitors at an emotional level and had the potential to enhance the physical experience of being at an historical place. The implemented prototype is visitor-aware personalised multi-point auditory narrative system that automatically plays sounds and stories depending on a combination of features such as physical location, visitor proximity and visitor preferences. The curators created for the trail multiple narratives to capture the different voices of the War. The stories are all personal accounts (as opposed to objective and detached reporting of the facts); they were designed to trigger empathy and understanding while leaving the visitors free to interpret the content and the place on the bases of their own understanding and sensitivity. The result is an evocative embodied experience that does not describe the place in a traditional sense, but leaves its interpretation open. It takes visitors beyond the traditional view of heritage as a source of information toward a sensorial experience of feeling the past. A prototype was set up and tested with a group of volunteers showing that a design that carefully combines content design, sound design, tangible and embodied interaction can bring archaeological remains, with very little to see, back to file

Short-Term Exposure to Bisphenol A Does Not Impact Gonadal Cell Steroidogenesis In Vitro

: Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 µM BPA perturbs luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1, CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (>= 18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

High plasma levels of ghrelin and des-acyl ghrelin in responders to antiepileptic drugs

OBJECTIVE: To reconsider ghrelin and des-acyl ghrelin plasma levels in children with epilepsy in order to establish a possible relation with response to antiepileptic drugs (AEDs). METHODS: We designed an observational study in which 114 patients with epilepsy were classified as responders (77) or nonresponders (37) and compared to 59 controls. In these patients, we measured ghrelin and des-acyl ghrelin by immunoassays in blood samples obtained after overnight fast. RESULTS: Ghrelin plasma levels were higher (+94%; p < 0.001, Dunn test) in responders compared to controls. Des-acyl ghrelin plasma levels were also higher in the same group (+55%; p < 0.001). In addition, both hormones were unmodified in nonresponders compared to controls. By comparing responders to nonresponders, ghrelin and des-acyl ghrelin, respectively, were +126% (p < 0.001) and +29% (p < 0.001) in patients with a positive response to AEDs. CONCLUSIONS: These results indicate that ghrelin and des-acyl ghrelin plasma levels are especially high in patients with epilepsy who positively respond to AEDs. In view of the anticonvulsant properties of ghrelin and des-acyl ghrelin, we propose that their higher levels could play a role in modulating the response to AEDs. Moreover, these peptides could be promising markers of response to AEDs

Effects of chronic administration of the phosphodiesterase inhibitor vardenafil on serum levels of adrenal and testicular steroids in men with type 2 diabetes mellitus

Background. Steroidogenesis is a complex enzymatic pro- cess in which cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) play an important role. Phosphodiesterase-5 inhibitors(PDE5i) increase cGMP, improving NO availability. Objective. To investigate whether long-term, chronic treat- ment with the PDE5i Vardenafil affects adrenal and testicular steroidogenesis in diabetic men, using liquid chromatography- mass spectrometry (LC-MS/MS). Design. A longitudinal, prospective, investigator-started, randomized, placebo-controlled, double-blind, clinical-trial was carried out. Setting and participants. 54 male patients affected by T2DM diagnosed within the last 5 years were enrolled. 26 and 28 patients were assigned to the verum and placebo-group, re- spectively. Interventions. The study consisted of an enrolment phase, a treatment phase (24 weeks) (Vardenafil/placebo 10 mg twice- daily), and a follow-up phase (24 weeks). Outcome measurements. Progesterone (P), 17-hydroxy- progesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), corticosterone, 11-deoxycortisol and cortisol (C), were evalu- ated using LC-MS/MS. Results. No differences were seen in sex testicular steroids between study and control group. For the adrenal gland, steroids were considered according to the zona in which they are pro- duced. Considering steroids produced in the zona fasciculata, no significant differences were seen in 11-deoxycortisol and C among visits, both in the study and in the control group. For the zona reticularis, DHEA significantly decreased during treatment only in the study group (p=0.007). At post-hoc test DHEA showed higher levels at visit 2 and 8 than in other visits. The DHEAS/DHEAS ratio significantly increased during treatment only in the verum group. Considering the adrenal zona glomeru- losa, corticosterone significantly changed among visits both in the study and in the control group (p&lt;0.001). At post-hoc test, in ПРОБЛЕМЫ ЭНДОКРИНОЛОГИИ, 5, 2016 both groups, corticosterone was significantly higher at visit 2 (p=0.028), 8 (p=0.003) and 10 (p=0.044), i.e. in coincidence with the complete clinical and instrumental examination per- formed only at these visits according to the study protocol. Conclusions. This is the first double-blind, placebo-con- trolled clinical-trial in which steroidogenesis is extensively in- vestigated by LC-MS/MS in T2DM men chronically treated with Vardenafil for 6 months, and followed-up for 6 months after therapy-withdrawal. Chronically administered Vardenafil reduces DHEA levels and increases DHEAS/DHEA ratio as possible consequences of modulation of steroidogenic enzymes by tissue changes in cGMP and/or cAMP availability. A possi- bly stress-related increase in corticosterone is suggested for the first time