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Novara di Sicilia, Italy

Lazzari C.,University of Padua | Peggion C.,University of Padua | Stella R.,University of Padua | Massimino M.L.,CNR Institute of Neuroscience | And 3 more authors.
Journal of Neurochemistry | Year: 2011

The cellular prion protein (PrPC) is a cell-surface glycoprotein mainly expressed in the CNS. The structural conversion of PrPC generates the prion, the infectious agent causing transmissible spongiform encephalopathies, which are rare and fatal diseases affecting animals and humans. Despite decades of intensive research, the mechanism of prion-associated neurodegeneration and the physiologic role of PrPC are still obscure. Recent evidence, however, supports the hypothesis that PrPC may be involved in the control of Ca2+ homeostasis. Given the universal significance of Ca2+ as an intracellular messenger for both the life and death of cells, this possibility may help explain the complex, often controversial, dataset accumulated on PrPC physiology, and the events leading to prion-associated neuronal demise. In this study, we have compared local Ca2+ movements in cerebellar granule neurons (CGN) derived from wild-type (WT), or PrP-knockout (KO), mice, by means of the Ca 2+-sensitive photo-probe, aequorin, genetically targeted to specific intracellular domains and delivered to CGN by lentiviral vectors. The use of an aequorin that localizes to the cytosolic domains proximal to the plasma membrane has allowed us to demonstrate that there was a dramatic increase of store-operated Ca2+ entry in PrP-KO CGN compared to WT neurons. Notably, this phenotype was rescued upon restoring PrPC expression. The Ca2+-phenotype of PrP-KO neurons can in part be explained by the lower expression of two major Ca2+-extruding proteins, namely the plasma membrane and the sarco-endoplasmic reticulum Ca2+-ATPases. The lower sarco-endoplasmic reticulum Ca2+-ATPase content may also contribute to explain why PrP-KO CGN accumulated less Ca2+ in the endoplasmic reticulum than the WT counterpart. © 2011 International Society for Neurochemistry.

Franzellitti S.,University of Bologna | Viarengo A.,University of Oriental Piedmont | Dinelli E.,University of Bologna | Fabbri E.,University of Bologna
Aquatic Toxicology | Year: 2012

The present study evaluated the effects of Cr(VI) in digestive gland of the Mediterranean mussel (Mytilus galloprovincialis) exposed for 1 week to the metal at 1, 10, and 50. ng/L. Tissue accumulation of Cr and lysosomal biomarkers were measured. Moreover, a low-density DNA microarray was used to identify early molecular markers of metal exposure. A concentration-dependent increase in tissue Cr concentrations was observed in both digestive gland and remaining soft tissues. A reduction of lysosomal membrane stability was detected in digestive gland at 10 and 50. ng/L of Cr(VI), indicating a loss of cell functional integrity. The expression of mRNAs encoding 13 genes involved in metal resistance (mt10, mt20), molecular chaperoning (hsp70), immune response (mytlB, mytcA and lys), transcriptional (histones h1, h2-a and h4), and antioxidant/detoxification (cat, mrp2, mvp) processes were significantly altered already at the lowest Cr(VI) concentration, where the effects at the histological level were nonsignificant. Altogether, data point out that depending on the exposure concentration Cr(VI) may cause or not oxidative stress altering the efficiency of the antioxidant system in counteracting the effects of Cr as a redox-active metal. Moreover, changes of mRNA expression profiles induced by Cr(VI) concentrations as low as 1-50. ng/L were related to altered immunomodulation, DNA stability, and stress response pathways previously proven to be affected by the metal. The molecular targets presently identified may drive the development of new biomarkers for Cr exposure or help their interpretation. © 2012 Elsevier B.V.

Ridone S.,University Hospital Maggiore della Carita of Novara | Matheoud R.,University Hospital Maggiore della Carita of Novara | Valzano S.,University Hospital Maggiore della Carita of Novara | Di Martino R.,University of Oriental Piedmont | And 2 more authors.
Physica Medica | Year: 2013

In order to evaluate the safety of the individual protection devices, the permeability of four different types of disposable gloves, commonly used in hospitals, was tested in relation to [99mTc]-pertechnetate and to [18F]-fluorodeoxyglucose ([18F]-FDG).From these radiopharmaceutical solutions, a drop was deposited on the external surface of the glove which was opened and stretched with the external surface placed upward. The smear test technique permitted to evaluate the activity onto the inner surface of the glove at different times. The smear tests were measured in a well sodium iodide detector calibrated in efficiency for 99mTc and 18F. The permeability was tested on ten samples of each type of gloves and was expressed as the ratio of the activity onto the inner surface at each time interval to the activity deposited on the external surface of the glove. For each type of gloves and for each sampling time, mean value, standard deviation and percentage coefficient of variation of permeability were evaluated. One type of gloves showed a low resistance to permeation of both radiopharmaceuticals, while another one only to pertechnetate. The other gloves were good performers.The results of this study suggest to test permeability for gloves used for handling radiopharmaceuticals, before their adoption in the clinical routine. This practice will provide a more careful service of radiation protection for nuclear medicine department staff. © 2013 Associazione Italiana di Fisica Medica.

Franzellitti S.,University of Bologna | Capuzzo A.,University of Ferrara | Viarengo A.,University of Oriental Piedmont | Fabbri E.,University of Bologna
Comparative Biochemistry and Physiology - C Toxicology and Pharmacology | Year: 2011

The aim of this study was to infer putative interactive effects of a binary mixture between nickel (Ni) and chlorpyrifos (CHP) on mussel cell signaling, and also to unravel downstream effects on transcriptional regulation mediating cytoprotective responses. Mussels were exposed for 4 days to Ni (0.77 mg/L), CHP (4.5 mg/L), or the mixture Ni/CHP (0.135 mg/L Ni and 0.61 mg/L CHP). Cyclic AMP content and PKA activity in gills were evaluated as biological endpoints related to cell signaling. Expression of the MgPgp (ABCB1) and MgMvp genes was also assessed as involved in the mussel MXR mechanism. Levels of cAMP and PKA activities were not modified in mussels exposed to Ni or CHP, whereas they significantly increased in organisms exposed to the mixture. Similar responses were also detected for MgPgp expression, which is thought to be under cAMP/PKA-mediated regulation. Expression of MgMvp was unaffected by CHP or Ni/CHP exposure, and increased by Ni. The differential regulation of MgPgp and MgMvp expressions could be ascribed to the different intracellular localization and function of the two transporters. On the whole, present data indicated that Ni and CHP elicited interactive effects on mussel physiology, both at the signal transduction and at the gene expression levels. © 2011 Elsevier Inc. All rights reserved.

Tampellini M.,University of Turin | Polverari R.S.,University of Turin | Ottone A.,University of Turin | Alabiso I.,University of Turin | And 10 more authors.
Chronobiology International | Year: 2015

Seasonal variation of baseline diagnosis (or clinical suspect) of stage I-III colorectal cancer patients has been repeatedly reported as an independent variable influencing overall survival. However, data are conflicting and no information is available about such a rhythm in advanced stage patients. To test whether a circannual rhythm of efficacy outcomes can be detected in this setting, we collected data about response rate (RR), progression-free survival (PFS), and overall survival (OS) to first-line chemotherapy of 1610 newly diagnosed metastatic patients treated at four independent centers. Responses to first-line chemotherapy were available for 1495 patients. A strong circannual rhythm in RR was evident, with the higher proportion of responding patients in the subgroup diagnosed in January (acrophase). At the time of data cutoff, 1322 patients progressed and 986 died, with median PFS and OS of 11 and 25.6 months, respectively. A circannual rhythmicity of the proportion of patients progressing at 6 months and surviving at 1 year was demonstrated, with acrophases located both in winter (February and January, respectively), similar to what reported for RR. Several interpretations about the genesis of this cyclic variation could be claimed: the rhythm in sunlight exposure and, as a consequence, of vitamin D serum levels and folate degradation, the variability in toxic effect intensity of chemotherapy, and the rhythm in the biological behavior of tumor cells. This observation is worth of further investigation both in preclinical and in clinical settings in order to better elucidate the underlying mechanisms. © 2015 Taylor & Francis Group, LLC.

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