Article: Effects of Cholecalciferol Supplementation in Patients with stable heart failure and LOw vITamin D levels (ECSPLOIT-D): a double-blind, randomized, placebo-controlled pilot study - Minerva Cardioangiologica 2017 December;65(6):553-62 - Minerva Medica - Journals

Children with epilepsy and identified as responders to antiseizure medications (ASMs) were found to present markedly higher ghrelin plasma levels when compared to drug-resistant patients. However, it was undetermined if this phenotype could be influenced by the ASMs. Here, we prospectively investigated total ghrelin and des-acyl ghrelin (DAG) plasma levels by enzyme-linked immunosorbent assay before and after ASM administration. Inclusion criteria were: (i) subject with a suspicion of epilepsy; (ii) age ranging from 0 to 16 years; and (iii) informed consent signed by parents or caregivers. Exclusion criteria were acute or chronic metabolic disorders with occasional convulsions but without epilepsy. Fifty patients were followed over a period of one year in Italian neuropediatric centers. Apart from a few exceptions, the majority of children were responsive to ASMs. No differences were found in total ghrelin and DAG levels before and after the treatment, but total ghrelin levels were significantly lower in children with generalized epilepsy compared to those with combined focal and generalized epilepsy. Moreover, the ghrelin-to-DAG ratio was also markedly lower in generalized epilepsies compared to all the other types of epilepsy. Finally, ghrelin was unchanged by ASMs, including the first (e.g., carbamazepine), second (levetiracetam), and third (lacosamide) generation of anticonvulsants.

The present study is the second step (concerning normal diet restoration) of the our previous study (concerning the calcium-free diet) to determine whether normal diet restoration, with/without concomitant PTH (1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in the rat model. The final goals are (i) to define timing and manners of bone mass changes when calcium is restored to the diet, (ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e., trabecular versus cortical bone), and (iii) to verify the eventual role of PTH (1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical bone, in response to different levels of calcium content in the diet, and the effect of PTH, mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are (i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone’s response to dietary/metabolic alterations and (ii) the evidence that the more involved bony architecture is the trabecular bone, the most susceptible to the dynamical balance of the two homeostases.

Background. Intense physical exercise influences the secretion of hormones involved in several metabolic processes. In particular, an acute cortisol (C) and growth hormone (GH) increase after an acute physical activity is widely demonstrated in literature. Moreover, the testosterone (T)/C ratio was recently proposed as a performance index in male athletes. On the contrary, little is known about hormonal changes in women under physical activity and only few studies evaluated the hormonal trend in an extended period of time. Aim. To evaluate the hormonal changes during an annual volleyball female regular season. Methodology. A longitudinal, retrospective, observational clinical trial was carried out. 28 female professional volleyball players belonging to the same team were enrolled. For each subject, blood samples were collected after 36 hours of rest in four visits. Visit 1 was performed at the beginning of the training phase, visit 2 and 3 were performed during and Visit 4 were performed at the end of the regular season. GH, insulin-like growth factor (IGF)-1, T and C were assessed by immunoenzimatic assays. Results. Both GH and IGF-1 were above the normal range at visit 1 (5.08 ± 5.22 ng/ml; 265.88 ± 105.85 ng/ml). In particular, five athletes had GH above the normal range (17.8%). No alterations of other hormones were found at Visit 1. C significantly changed during the regular season (p=0.009), with higher levels at Visit 2 (p=0.049), compared to visit 1 and the following visits. Similarly, T significantly changed during the season (p=0.013), even if a clear trend was not demonstrated. The post-hoc test showed two peaks of T at Visit 2 and Visit 4 (p=0.029 and p=0.024, respectively). Accordingly, the T/C ratio significantly changed during visits (p=0.009), decreasing of about 30% in the first phase of the regular season, suggesting an overreaching of subjects enrolled. Conclusion. Here we found that chronic intense physical activity influences hormonal levels in female volleyball players. In particular, C secretion is increased at the beginning of the regular season, whereas T serum levels shows a significant fluctuation during the regular season. Moreover, we suggest that T/C ratio could be useful in the evaluation of the training overload in female athletes.

Background. Steroidogenesis is a complex enzymatic process 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 treatment 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, respectively. Interventions. The study consisted of an enrolment phase, a treatment phase (24weeks) (Vardenafil/placebo 10mg twice-daily), and a follow-up phase (24weeks). Outcome measurements: progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), corticosterone, 11-deoxycortisol and cortisol (C), were evaluated 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 produced. 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 glomerulosa, corticosterone significantly changed among visits both in the study and in the control group (p<0.001). At post-hoc test, in 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 performed only at these visits according to the study protocol. Conclusions. This is the first double-blind, placebo-controlled clinical-trial in which steroidogenesis is extensively investigated 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 possibly stress-related increase in corticosterone is suggested for the first time.