De Minicis S.,Marche Polytechnic University |
Agostinelli L.,Marche Polytechnic University |
Rychlicki C.,Marche Polytechnic University |
Sorice G.P.,Catholic University of the Sacred Heart |
And 14 more authors.
PLoS ONE | Year: 2014
NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl 4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+ CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD. © 2014 De Minicis et al.
Plantone D.,Regina Elena Cancer Institute |
Plantone D.,Catholic University of the Sacred Heart |
Primiano G.,Catholic University of the Sacred Heart |
Renna R.,Regina Elena Cancer Institute |
And 5 more authors.
Journal of Spinal Cord Medicine | Year: 2015
Context: Copper deficiency myelopathy represents an often underdiagnosed, acquired neurological syndrome, clinically characterized by posterior column dysfunction. The main causes of copper deficiency are bariatric surgery, increased consumption of zinc, and malabsorption. However, even after a careful history taking and extensive laboratory researches, the etiology of copper deficiency remains undetermined in a significant percentage of cases. Patients affected by copper deficiency myelopathy usually present with sensory ataxia due to dorsal column dysfunction and sometimes with mild leg spasticity. In such patients, spinal cord magnetic resonance imaging (MRI) may show hyperintense lesions in T2-weighted sequences involving the posterior columns of cervical and thoracic cord. These MRI findings are not distinguishable from those of subacute combined degeneration associated with vitamin B12 deficiency. Findings: Here, we describe two patients with gait ataxia and sensory symptoms in which a diagnosis of copper deficiency myelopathy was made. Both patients showed a significant clinical, neuroradiological, and neurophysiological improvement after proper supplementation therapy. Conclusion: The patients herein described underline the importance to include serum copper and ceruloplasmin levels as part of the myelopathy diagnostic workup, especially in the cases of otherwise unexplained subacute myelopathy involving the posterior columns. Since copper deficiency myelopathy is a progressive syndrome, early diagnosis is mandatory in order to promptly provide a proper supplementation therapy and, thus, prevent an irreversible neurological damage. © The Academy of Spinal Cord Injury Professionals, Inc. 2015.
Laurita R.,University of Bologna |
Alviano F.,University of Bologna |
Marchionni C.,University of Bologna |
Abruzzo P.M.,University of Bologna |
And 11 more authors.
Journal of Physics D: Applied Physics | Year: 2016
The effect of an atmospheric pressure non-equilibrium plasma on human mesenchymal stem cells was investigated. A dielectric barrier discharge non-equilibrium plasma source driven by two different high-voltage pulsed generators was used and cell survival, senescence, proliferation, and differentiation were evaluated. Cells deprived of the culture medium and treated with nanosecond pulsed plasma showed a higher mortality rate, while higher survival and retention of proliferation were observed in cells treated with microsecond pulsed plasma in the presence of the culture medium. While a few treated cells showed the hallmarks of senescence, unexpected delayed apoptosis ensued in cells exposed to plasma-treated medium. The plasma treatment did not change the expression of OCT4, a marker of mesenchymal stem cell differentiation. © 2016 IOP Publishing Ltd.
Mondelli M.,Local Health Unit |
Aretini A.,Local Health Unit |
Ginanneschi F.,University of Siena |
Padua L.,Catholic University |
Padua L.,Don Gnocchi Foundation Onlus
Journal of Clinical Neurophysiology | Year: 2010
Purpose: To report an electrophysiological study on thenar motor neuropathy of the median nerve. Methods: Twenty-eight consecutive patients (mean age, 48.8 years; 17 men) with dominant hand thenar muscle weakness without sensory symptoms were enrolled in this study. Electromyography of hand and forearm muscles and neurography of median, ulnar, radial, and palmar nerves, including distal motor latency recording from the second interosseous-lumbrical muscles, were performed. Results: Complete denervation of the abductor pollicis brevis muscle was observed in one case and delayed median abductor pollicis brevis-distal motor latency was observed in the others. Other neurographic findings were normal. Conclusions: Thenar motor neuropathy may have different pathogeneses. It may be considered a variant of carpal tunnel syndrome involving the motor branch only or more likely due to chronic direct compression of the branch, because it preferentially affects males, dominant hand, and persons doing manual work. In both cases, anatomic origin and variations in the course of the branch may favor thenar motor neuropathy. Copyright © 2010 by the American Clinical Neurophysiology Society.
Masciullo M.,Catholic University of the Sacred Heart |
Masciullo M.,Don Gnocchi Foundation ONLUS |
Santoro M.,Catholic University of the Sacred Heart |
Santoro M.,Don Gnocchi Foundation ONLUS |
And 9 more authors.
Journal of Inherited Metabolic Disease | Year: 2010
GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides. It has been proposed that substrate reduction therapy using N-butyl- deoxynojirimycin (miglustat) may delay neurological progression, at least in late-onset forms of GM2 gangliosidosis. We report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. The follow-up included serial neurological examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive, brain, and muscle MRI studies. We document some minor effects on neurological progression in chronic Sandhoff disease by miglustat treatment, confirming the necessity of phase II therapeutic trials including early-stage patients in order to assess its putative efficacy in chronic Sandhoff disease. © SSIEM and Springer 2010.