Papers by Annamaria Morelli
The Journal of Sexual Medicine, 2016
citrate concentration (secreted by the prostate) were evaluated before and after the end of the t... more citrate concentration (secreted by the prostate) were evaluated before and after the end of the treatment in each of groups A and B and before and at the end of the 12-week-experimental period (EP) in group C, respectively. Serum levels of testosterone were evaluated before and at the end of the EP in each of groups A, B, or C. Wilcoxon paired test was used for statistical analysis. A probability P smaller than 0.05 was considered as significant. Results: Within group A the peripheral serum mean testosterone concentration (ng/ml), semen citrate concentration (mg/dl), percentage of motile spermatozoa (%), the mean LMP (micrometers), the %HOST (%) and percentage of morphologically normal spermatozoa (%) were significantly greater after avanafil treatment (8.85 , 385, 39, 4.5, 59, and 9, respectively) than before treatment (7.99, 297, 26, 4.1, 46, and 3, respectively). Within each group B and C, differences in the above parameters prior to the EP and at the end of the EP were not significant. Conclusion: The enhancement of prostatic secretory function, the longer LMP, and the increase in testosterone may explain the increase in sperm motility after avanafil administration. Policy of full disclosure: None.
International Journal on Disability and Human Development, 2001
ABSTRACT
Journal of Surgical Research, 2001
Background. Patients affected by hypoparathyroidism of variable etiology are currently treated wi... more Background. Patients affected by hypoparathyroidism of variable etiology are currently treated with exogenously administered vitamin D and calcium. Human parathyroid transplantation has long been investigated as a possible mean of treating these patients to prevent long-term hypocalcemia. However, the main obstacle for this treatment is represented by tissue rejection. A reliable method to efficiently protect the transplanted tissue from rejection and to allow longterm survival of the graft is the encapsulation of tissues or cells in alginate-polylysine-alginate membranes, which were successfully used for encapsulation of islets of Langerhans. The microencapsulation of parathyroid tissue fragments or of parathyroid cells becomes, therefore, a potential approach for the successful treatment of permanent symptomatic hypoparathyroidism without pharmacological immunosuppression. Materials and methods. We describe microencapsulation of differentiated human parathyroid cells derived from adenoma or hyperplastic glands. Longterm viability, cell growth, and parathyroid hormone production of microencapsulated cells were evaluated together with responsiveness to extracellular Ca 2؉. Results. Microencapsulated parathyroid cells maintained proliferative and differentiative properties for a long term in culture with a good response to extracellular Ca 2؉ concentration. Conclusions. These findings represent a crucial step toward the construction of functional bioartificial parathyroid organoids for the treatment of hypoparathyroidism in humans.
Biochemical and Biophysical Research Communications, 1999
Telomerase results to be active in human germ, stem cells, several malignant cell tumors and in i... more Telomerase results to be active in human germ, stem cells, several malignant cell tumors and in immortalized cell lines. In order to investigate if molecular mechanisms other than Rb gene inactivation can be helpful to diagnose malignancy of parathyroid tumors, we decided to investigate the presence of active telomerase in homogenates from different pathological parathyroid tissues (hyperplastic, adenomatous, carcinomatous, and normal) and primary cell cultures. The TRAP assay was performed to detect this activity in histologically characterized normal, hyperplastic, adenomatous, and carcinomatous human parathyroid tissues, primary cell lines, and one metastatic tissue from parathyroid carcinoma. Only malignant parathyroid glands and the metastatic tissue were TRAP positive. Our findings suggest that telomerase expression could represent an important molecular mechanism underlying the acquisition and progression of an aggressive phenotype of epithelial parathyroid cells and it may help to predict their malignant potential. The TRAP assay is easy to perform and it could become an additional tool to be included in the harmamentarium for the molecular diagnosis of parathyroid carcinoma.
vitamin D receptor agonist elocalcitol up-regulates L-type calcium channel activity in
Journal of Molecular Endocrinology, 2020
Chronic inflammation is involved in the genitourinary syndrome of menopause (GSM) and beneficial ... more Chronic inflammation is involved in the genitourinary syndrome of menopause (GSM) and beneficial effects of androgens in the vagina have been described. We investigated the potential involvement of human vagina smooth muscle cells (hvSMCs) in the inflammatory response and the immunomodulatory effect of androgen receptor (AR) agonist dihydrotestosterone (DHT). HvSMCs isolated from menopausal women were evaluated for sex steroids receptors and toll-like receptors mRNA expression, and left untreated or treated in vitro with lipopolysaccharide (LPS) or IFNγ, in the presence or absence of DHT. We evaluated mRNA expression (by RT-PCR) and secretion in cell culture supernatants (by a bead-based immunoassay) of pro-inflammatory markers. Nuclear translocation of NF-κB (by immunofluorescence) and cell surface HLA-DR expression (by flow cytometry) were also evaluated. Similar experiments were repeated in rat vSMCs (rvSMCs). In hvSMCs and rvSMCs, AR was highly expressed. DHT pre-treatment inhib...
Italian journal of anatomy and embryology, 2017
The primary cilium is a non-motile sensory antenna protruding from the surface of nearly all cell... more The primary cilium is a non-motile sensory antenna protruding from the surface of nearly all cells of the body, able to mediate the cellular response to extracellular signals. Although many of its functions remain to be clarified, it has been recently shown a role in neurogenesis [1]. In this study we evaluated the presence of the primary cilium in neurons isolated from the human fetal nucleus basalis of Meynert (hfnbM), a basal forebrain region crucially involved in the cholinergic transmission required for learning and memory. The hfnbM cells are characterized by the expression of cholinergic markers, such as choline acetyl transferase (ChAT) and also express the primary cilium, which, in basal conditions, was detected in the 17% of cells. It is known that nerve growth factor (NGF) supports survival, maintenance, connectivity and function of the brain cholinergic neurons. Indeed, we demonstrated that hfnbM cells respond to NGF in terms of proliferation, neurite formation and ChAT ...
Journal of chemical neuroanatomy, 2018
Human striatal precursor cells (HSPs) isolated from ganglionic eminence may differentiate in elec... more Human striatal precursor cells (HSPs) isolated from ganglionic eminence may differentiate in electrophysiologically functional excitable neuron-like cells and a number of endogenous molecules such as hormones, neurotransmitters or growth factors can actually regulate neuronal growing and differentiation. The purpose of this research was to assess, by electrophysiological and immunocytochemical analysis, if the type of culture medium could specifically impact on the neuronal differentiation potential of HSPs. Accordingly, HSPs were maintained in different inductive media such as cortical and spinal cord conditioned media, and we estimated the possible changes in the main ion currents, excitability and expression of neuronal markers indicative of neuronal differentiation. Our results have shown that 36 h exposure to each of the conditioned media, with their blend of autocrine and paracrine growth factors, was able to modify significantly the electrophysiological membrane properties an...
Acta histochemica, 2018
Several investigations have demonstrated neuroprotective effects of quercetin, a polyphenol widel... more Several investigations have demonstrated neuroprotective effects of quercetin, a polyphenol widely present in nature, against neurotoxic chemicals, as well as in neuronal injury/neurodegenerative disease models. Most of these studies have been performed with quercetin aglycone and its metabolites, while scanty data are available on its glycosides. This study is aimed at investigating the neuroprotective effects of quercetin 3,4'-O-β-d-diglucoside (Q3,4'dG), isolated from the bulbs of the white cultivar (Allium cepa L.), using an in vitro model of human striatal precursor cells (HSPs), a primary culture isolated from the striatal primordium and previously characterized. To study the effect of Q3,4'dG on cell survival, HSPs were exposed to nutrient deprivation created by replacing culture medium with phosphate buffer saline (PBS). Our findings showed that Q3,4'dG treatment significantly promoted cell survival and strongly decreased apoptosis induced by nutrient depriva...
Molecular and Cellular Neuroscience, 2016
Over the past decades, studies in both Huntington's disease animal models and pilot clinical tria... more Over the past decades, studies in both Huntington's disease animal models and pilot clinical trials have demonstrated that replacement of degenerated striatum and repair of circuitries by grafting fetal striatal primordium is feasible, safe and may counteract disease progression. However, a better comprehension of striatal ontogenesis is required to assess the fetal graft regenerative potential. During neuronal development, neurotrophins exert pleiotropic actions in regulating cell fate and synaptic plasticity. In this regard, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are crucially implicated in the control of fate choice of striatal progenitor cells. In this study, we intended to refine the functional features of human striatal precursor (HSP) cells isolated from ganglionic eminence of 9-12 week old human fetuses, by studying with electrophysiological methods the effect of BDNF and FGF2 on the membrane biophysical properties and the voltage-dependent Ca 2+ currents. These features are particularly relevant to evaluate neuronal cell functioning and can be considered reliable markers of the developmental phenotype of human striatal primordium. Our results have demonstrated that BDNF and FGF2 induced membrane hyperpolarization, increased the membrane capacitance and reduced the resting total and specific conductance values, suggesting a more efficient control of resting ionic fluxes. Moreover, the treatment with both neurotrophins enhanced N-type Ca 2+ current amplitude and reduced Land T-type ones. Overall, our data indicate that BDNF and FGF2 may help HSP cells to attain a more functionally mature phenotype.
Italian journal of anatomy and embryology, 2014
Frontiers in Cellular Neuroscience, 2015
European Urology Supplements, 2012
Endocrine Abstracts, 2014
Virchows Archiv, 1995
The gene responsible for multiple endocrine neoplasia type I (MEN-l) syndrome has been mapped to ... more The gene responsible for multiple endocrine neoplasia type I (MEN-l) syndrome has been mapped to chromosome l lq13. It appears to function as a tumoursuppressor gene analogous to that for retinoblastoma and allelic losses involving the wild-type of the MEN-1 allele have been found in parathyroid and pancreatic endocrine tumours of MEN-1 patients. No genetic information has been provided so far on non-endocrine malignancies that may occur in MEN-1 patients, A case of exocrine pancreatic adenocarcinoma presenting as the terminal event in a woman with a long standing history of MEN-1 syndrome and multiple endocrine tumours of the pancreas was investigated for possible allelic losses at the MEN-1 gene locus using restriction fragment length polymorphisms (RFLPs) closely linked to the MEN-1 gene and polymerase chain reaction (PCR) for DllS533 locus. No allelic losses were found in tumour tissue with two informative RFLPs (D11S97, D11S 146) or with PCR analysis. These findings suggest that the MEN-1 gene does not confer a predisposition to develop tumours other than those that typify the syndrome.
The Prostate, 2009
BACKGROUND. Benign prostatic hyperplasia (BPH) is characterized by an important inflammatory comp... more BACKGROUND. Benign prostatic hyperplasia (BPH) is characterized by an important inflammatory component. Stimulation of human prostate stromal cells from BPH tissues with proinflammatory cytokines leads to secretion of IL-8, a chemokine involved in BPH pathogenesis. The vitamin D receptor (VDR) agonist elocalcitol can arrest prostate growth in BPH patients, but its mechanism of action in this pathology is still incompletely understood. METHODS. IL-8 levels were measured by real-time RT-PCR and ELISA. NF-kB translocation and COX-2 expression were evaluated by confocal microscopy. RhoA and Rho-kinase (ROCK) gene expression and functional activity were studied by real-time RT-PCR, immuno-kinase assays, Western blot analysis, confocal microscopy, and cell invasion. RESULTS. Stimulation of BPH cells with IL-8 activates the calcium-sensitizing RhoA/ROCK pathway, as demonstrated by the increased membrane translocation of RhoA and by phosphorylation of the ROCK substrate myosin phosphatase target subunit 1 (MYPT-1). In agreement with these data, C3 exoenzyme, a selective RhoA inhibitor, inhibits IL-8-induced invasion of BPH cells. The VDR agonist elocalcitol significantly inhibits IL-8 production by BPH cells stimulated with inflammatory cytokines, and IL-8-induced proliferation of BPH cells. In addition, elocalcitol inhibits IL-8-induced membrane translocation of RhoA and MYPT-1 phosphorylation in BPH cells, and inhibits dose-dependently their IL-8-dependent invasion. The inhibition induced by elocalcitol of IL-8 production by BPH cells is accompanied by decreased COX-2 expression and PGE 2 production and by arrest of NF-kB p65 nuclear translocation, associated with inhibition of the RhoA/ROCK pathway. CONCLUSIONS. These data provide a mechanistic explanation for the anti-proliferative and anti-inflammatory properties of elocalcitol in BPH cells.
The Prostate, 2012
BACKGROUND. Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH) are often comorbid. C... more BACKGROUND. Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH) are often comorbid. Chronic inflammation, a determinant pathogenic factor for BPH, is a putative link between the two conditions. METHODS. In a multi-center cohort of BPH patients (n ¼ 244) who underwent prostatectomy, we evaluated whether MetS is associated with prostatic inflammation in BPH specimens. In addition, we investigated the in vitro inflammatory effects of metabolic insults on human prostatic myofibroblastic cells (hBPH). RESULTS. Inflammatory infiltrates score (IS) in prostatectomy specimens showed a stepwise association with the number of MetS factors present (P ¼ 0.001). After adjusting for age, reduced HDL cholesterol, and elevated triglycerides were the only factors significantly associated with IS. Increased IS was also significantly associated with hypogonadism. In an age-and testosterone (T)-adjusted model, dyslipidemia was still associated with IS. To investigate whether metabolic factors could directly trigger prostate inflammation, we performed preliminary studies in myofibroblastic hBPH. Among the different factors, oxidized lowdensity lipoprotein (oxLDL) showed the highest secretion of IL-8 (>10-fold)-a surrogate marker of prostate inflammation-as well as IL-6, and bFGF. Co-treatment with DHT significantly inhibited oxLDL-induced secretion of IL-8, whilst an AR-antagonist, bicalutamide, reversed DHT effects. DHT suppresses oxLDL receptor (LOX-1) expression. Additional supporting information may be found in the online version of this article.
PLoS ONE, 2012
Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment... more Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adenoassociated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9642.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2672 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile.
Molecular and Cellular Endocrinology, 2014
Rabbits with high fat diet (HFD)-induced metabolic syndrome (MetS) developed hypogonadotropic hyp... more Rabbits with high fat diet (HFD)-induced metabolic syndrome (MetS) developed hypogonadotropic hypogonadism (HH) and showed a reduced gonadotropin-releasing hormone (GnRH) immunopositivity in the hypothalamus. This study investigated the relationship between MetS and hypothalamic alterations in HFD-rabbits. Gonadotropin levels decreased as a function of MetS severity, hypothalamic gene expression of glucose transporter 4 (GLUT4) and interleukin-6 (IL-6). HFD determined a low-grade inflammation in the hypothalamus, significantly inducing microglial activation, expression and immunopositivity of IL-6, as well as GLUT4 and reduced immunopositivity for KISS1 receptor, whose mRNA expression was negatively correlated to glucose intolerance. Correcting glucose metabolism with obetcholic acid improved hypothalamic alterations, reducing GLUT4 and IL-6 immunopositivity and significantly increasing GnRH mRNA, without, however, preventing HFD-related HH. No significant effects at the hypothalamic level were observed after systemic anti-inflammatory treatment (infliximab). Our results suggest that HFDinduced metabolic derangements negatively affect GnRH neuron function through an inflammatory injury at the hypothalamic level.
The Journal of Urology, 2009
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Papers by Annamaria Morelli