40 research outputs found
Silibinin, an HSP90 Inhibitor, on Human ACTH-Secreting Adenomas
No full textIntroduction. The glucocorticoid receptor is pivotal to control corticotrophin (ACTH) secretion and its function is closely linked to the heat shock protein 90 (HSP90) chaperone complex. Impaired sensitivity to glucocorticoid feedback is a hallmark of human corticotroph adenomas, i.e., Cushing's disease, a disorder with few medical treatment options. Silibinin, a HSP90 inhibitor, has been studied in tumoral corticotroph cells and its use proposed in Cushing's disease. Aim of the present study was to further investigate the effect of silibinin on human corticotroph adenomas in vitro.Methods. Seven human ACTH-secreting pituitary adenomas were established in culture and treated with 10 - 50 mu M silibinin with/without dexamethasone for up to 72 hours. ACTH medium levels were measured and POMC and glucocorticoid receptor, i.e., NR3C1, gene expression assessed.Results. Silibinin reduced spontaneous ACTH secretion and restored sensitivity to steroid negative feedback to a different extent in individual adenomas. POMC expression was decreased both in control and dexamethasone-treated wells in specimens sensitive to silibinin. Interestingly, silibinin reduced constitutive NR3C1 expression and reversed the dexamethasone-induced inhibition.Conclusions. Our findings indicate that silibinin can inhibit ACTH synthesis and secretion in individual human corticotroph adenomas and directly affects NR3C1 gene expression. These results reveal promising effects of this HSP90 inhibitor on human corticotroph adenomas and support an innovative target treatment for patients with Cushing's disease
Elemental investigation on Spanish dinosaur bones by x-ray fluorescence
No full text"In this paper we examine the chemical composition results obtained on a collection of 18. dinosaur fossil bones from Spain studied using a portable x-ray fluorescence spectrometer. together with a reverse Monte Carlo numerical technique of data analysis. This approach is. applied to the hypothesis of arbitrarily rough surfaces in order to account for the influence of. the surface state of specimens on the chemical content evaluation. It is confirmed that the. chemical content of elements is essential for understanding the changes brought about by. diagenetic and taphonomic processes. However, for precise knowledge of what changes fossil. bones have undergone after animal life and burial, it is necessary to use a multi-technique. approach making use of other instruments like x-ray diffraction in order to describe accurately. the transformations undergone by the mineralogical and bioinorganic phases and the. properties of specific molecular groups.
Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas
No full textACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1,NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing’s disease pathophysiology
Malignancy course of pituitary adenoma in MEN1 syndrome: Clinical-Neuroradiological signs
No full textPituitary carcinomas (PCa) are extremely rare, indistinguishable from pituitary adenomas on histopathological grounds and have a poor prognosis. Most PCa start as PRL or ACTH secreting tumors in males, with relapsing invasive behaviour, refractoriness to medical and radiotherapy and increasing hormonal levels. The presence of distant metastases is still required for the diagnosis of PCa. The association with genetic endocrine diseases must be taken into account, since it adds further risk of evolution towards malignancy. Intradural spinal metastases have also been reported, so a complete craniospinal MR evaluation is recommended, when clinically indicated. We report a case of PCa, associated with MEN1 syndrome, with evidence of meningeal spread to the tentorium cerebelli, clival dura and spinal drop metastases mimicking spinal nerves schwannomas
Sexual Dimorphism in Cellular and Molecular Features in Human ACTH-Secreting Pituitary Adenomas.
No full textBackground. Cushing’s disease presents gender disparities in prevalence and clinical course. Little is known, however, about sexual dimorphism at the level of the corticotrope adenoma itself. The aim of the present study was to evaluate molecular features of ACTH-secreting pituitary adenomas collected from female and male patients with Cushing’s disease. (2) Methods. We analyzed 153 ACTH-secreting adenomas collected from 31 men and 122 women. Adenomas were established in culture and ACTH synthesis and secretion assessed in basal conditions as well as during incubation with CRH or dexamethasone. Concurrently, microarray analysis was performed on formalin-fixed specimens and differences in the expression profiles between specimens from male and female patients identified. (3) Results. ACTH medium concentrations in adenomas obtained from male patients were significantly lower than those observed in adenomas from female patients. This could be observed for baseline as well as modulated secretion. Analysis of corticotrope transcriptomes revealed considerable similarities with few, selected differences in functional annotations. Differentially expressed genes comprised genes with known sexual dimorphism, genes involved in tumour development and genes relevant to pituitary pathophysiology. (4) Conclusions. Our study shows for the first time that human corticotrope adenomas present sexual dimorphism and underlines the need for a gender-dependent analysis of these tumours. Differentially expressed genes may represent the basis for gender-tailored target therapy
Studio sistematico delle pretazioni e della procedura di calibrazione per un calorimetro elettromagnetico a Krypton liquido nell' Sambito della misura del parametro nel sistema
No full textA one-step solvothermal route for the synthesis of nanocrystalline anatase TiO2 doped with lanthanide ions
No full textA one-step solvothermal synthesis is proposed for the preparation of nanocrystalline single-phase TiO2 in the anatase form doped with lanthanide ions Eu3+, Er3+ and Sm3+. The structural properties of these products have been investigated by using X-ray powder diffraction, electron microscopy and Raman spectroscopy. Furthermore, the laser-excited luminescence spectra of the samples have been measured and analyzed. Following this route, the doping process turns out to be highly favorite and the resulting materials show an efficient luminescence in the visible regio
Shunt migration into the sphenoid sinus: case report
No full textOBJECTIVE AND IMPORTANCE: Shunt catheter,migration is, a potential. complication, of cerebrospinal fluid shunting procedures. We report an unusual case of proximal shunt migration into the sphenoid Sin,us. To our knowledge, there have, been,no previous reports of shunt migration through the bony structures of the cranial base.
CLINICAL PRESENTATION: A 41-year-old man who had,had a cyst-to-peritoneum shunt placed 21 years earlier for a temporal lobe arachnoid cyst presented with cerebrospinal fluid rhinorrhea. Neuroradiological imaging revealed migration of the shunt catheter through the medial wall of the middle temporal fossa into the sphenoid sinus:
INTERVENTION: The patient underwent shunt removal and repair of the dural defect. Intraoperatively, the proximal catheter tip was,found: in the sphenoid sinus with dural and bony erosion. The patient made an uneventful recovery.
CONCLUSION: We present a unique long-term complication associated with intracranial shunt catheters. We hypothesize that excessive proximal catheter length and. chronic cerebrospinal fluid pulsations contributed to migration of the catheter-in-to the sphenoid, sinus
Synthesis, Structural investigation and luminescence spectroscopy of nanocrystalline Gd3Ga5O12 Doped with lanthanide ions
No full textGadolinium gallium garnet (GGG) nanocrystalline powder doped with. lanthanide ions (Eu3+ and Er3+) have been obtained using two different methods (coprecipitation and Pechini). The X-ray diffraction results show that single phase cubic GGG nanopowders have been obtained for both preparation methods. The samples prepared by the two procedures show different morphologies, as revealed by scanning electron microscopy images. The Er3+-doped nanopowders obtained with the coprecipitation method show strong luminescence upon 488.0 nm excitation. The emission spectrum is similar to the one of the single crystal and of nanopowders of the same composition prepared by a combustion synthesis. The Er3+-doped GGG nanopowders obtained by the coprecipitation method show efficient upconversion in the green region (around 550 nm) upon excitation in the near IR at a wavelength of 800 nm
