Age-related variations in the growth hormone response to growth hormone secretagogues

Growth hormone (GH) secretagogues are synthetic peptidyl and non-peptidyl molecules which possess a strong, dose-dependent and reproducible GH-releasing effect after intravenous and even oral administration in humans. This effect is probably mediated via the activation of specific receptors, mainly present at the pituitary and hypothalamic level; a human pituitary GH secretogogue receptor has already been cloned, pointing to the existence of an endogenous GH secretagogue-like ligand. The GH-releasing effect of GH secretagogues is gender-independent but undergoes marked age-related variations. In fact, the effect is low at birth, increases markedly at puberty, persists at a similar level in adulthood and decreases thereafter, being already similar in middle age to that in elderly subjects. It is likely that the reduced activity of GH secretagogues in aging reflects the age-related changes in the neural control of somatotrope function. These could include the hypothetical impairment in the activity of the p..

Impatto del passaggio da denosumab ad alendronato sui valori di densità minerale ossea

n/

L'uso di statine diminuisce il rischio di orbitopatia in pazienti con nuova diagnosi di malattia di Graves-Basedow

n/

The Mineralocorticoid Agonist Fludrocortisone Promotes Survival and Proliferation of Adult Hippocampal Progenitors

Glucocorticoid receptor (GR) activation has been shown to reduce adult hippocampal progenitor cell proliferation and neurogenesis. By contrast, mineralocorticoid receptor (MR) signaling is associated with neuronal survival in the dentate gyrus of the hippocampus, and impairment of hippocampal MR has been linked to pathological conditions, such as depression or neurodegenerative disorders. Here, we aimed to further clarify the protective role of MR in adult hippocampal neurons by studying the survival and proliferative effects of the highly potent MR agonist fludrocortisone (Fludro) in adult rat hippocampal progenitor cells (AHPs), along with the associated signaling mechanisms. Fludro, which upregulated MR but not GR expression, increased survival and proliferation and prevented apoptosis in AHPs cultured in growth factor-deprived medium. These effects were blunted by the MR antagonist spironolactone and by high doses of the GR agonist dexamethasone. Moreover, they involved signaling through cAMP/protein kinase A (PKA)/cAMP response element-binding protein, phosphoinositide 3-kinase (PI3K)/Akt and its downstream targets glycogen synthase kinase-3β (GSK-3β) and mammalian target of rapamycin. Furthermore, Fludro attenuated the detrimental effects of amyloid-β peptide 1–42 (Aβ(1–42)) on cell survival, proliferation, and apoptosis in AHPs, and increased the phosphorylation of both PI3K/Akt and GSK-3β, which was reduced by Aβ(1–42). Finally, Fludro blocked Aβ(1–42)-induced hyperphosphorylation of Tau protein, which is a main feature of Alzheimer’s disease. Overall, these results are the first to show the protective and proliferative role of Fludro in AHPs, suggesting the potential therapeutic importance of targeting MR for increasing hippocampal neurogenesis and for treating neurodegenerative diseases

Interventional Radiology Approaches for Liver Metastases from Thyroid Cancer: A Case Series and Overview of the Literature

BACKGROUND: Liver metastases (LMs) from thyroid cancer (TC) are relatively uncommon in clinical practice and their management is challenging. Interventional radiology loco-regional treatments (LRTs), including radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE), have been successfully employed to treat LMs from various types of cancer. METHODS: We analyzed the role of LRTs in the management of unresectable LMs from differentiated and medullary TCs performed at our institution from 2015 to 2020. A review of the available English literature regarding this topic was also performed. RESULTS: Six hepatic LRTs were performed in 4 TC patients with LMs, in 2 cases after the start of treatment with a tyrosine kinase inhibitor (TKI). A partial response was obtained in 2 patients; the diameter of the largest targeted lesion was 18 mm in both of them. The remaining procedures were performed on larger lesions and a stable disease was achieved in all but one case. Acute LRT-related complications were transient and mild. In literature, the largest studies were focused on TACE in LMs from MTC, showing good tolerance and remarkable disease control, especially in case of limited liver tumour involvement. CONCLUSION: LRTs for LMs represent a valuable option for the treatment of metastatic TC in case of isolated hepatic progression or for symptoms relief, also after the start of TKI treatment as part of a multimodal approach. The best disease control is obtained when hepatic metastatic burden is limited. These procedures are generally well tolerated; however, a cautious multidisciplinary selection of the candidates is mandatory

Outcome riproduttivi e perinatali in donne con iperplasia surrenalica congenita: studio di coorte

n/