Barresi M.,University of Pisa |
Grasso C.,University of Pisa |
Bruschini L.,Pisa Hospital |
Berrettini S.,Pisa Hospital |
Manzoni D.,University of Pisa
Neuroscience | Year: 2012
Vestibulospinal reflexes elicited by head displacement become appropriate for body stabilization owing to the integration of neck input by the cerebellar anterior vermis. Due to this integration, the preferred direction of spinal motoneurons' responses to animal tilt rotates by the same angle and by the same direction as the head over the body, which makes it dependent on the direction of body displacement rather than on head displacement. It is known that the cerebellar control of spinal motoneurons involves the reticular formation. Since the preferred directions of corticocerebellar units' responses to animal tilt are tuned by neck rotation, as occuring in spinal motoneurons, we investigated whether a similar tuning can be observed also in the intermediate station of reticular formation. In anaesthetized rats, the activity of neurons in the medullary reticular formation was recorded during wobble of the whole animal at 0.156. Hz, a stimulus that tilted the animal's head by a constant amplitude (5°), in a direction rotating clockwise or counter clockwise over the horizontal plane. The response gain and the direction of tilt eliciting the maximal activity were evaluated with the head and body axes aligned and during a maintained body-to-head displacement of 5-20° over the horizontal plane, in either direction. We found that the neck displacement modified the response gain and/or the average activity of most of the responsive neurons. Rotation of the response direction was observed only in a minor percentage of the recorded neurons. The modifications of reticular neurons' responses were different from those observed in the P-cells of the cerebellar anterior vermis, which rarely showed gain and activity changes and often exhibited a rotation of their response directions. In conclusion, reticular neurons take part in the neck tuning of vestibulospinal reflexes by transforming a head-driven sensory input into a body-centred postural response. The present findings prompt re-evaluation of the role played by the reticular neurons and the cerebellum in vestibulospinal reflexes. © 2012 IBRO.
Panichi V.,Versilia Hospital |
Bigazzi R.,Livorno Hospital |
Paoletti S.,Versilia Hospital |
Mantuano E.,Livorno Hospital |
And 12 more authors.
Journal of Nephrology | Year: 2010
Background: Despite substantial progress in medical care, the mortality rate remains unacceptably high in dialysis patients. Evidence suggests that bone mineral dismetabolism (CKD-MBD) might contribute to this burden of death. However, to date only a few papers have investigated the clinical relevance of serum mineral derangements and the impact of different therapeutic strategies on mortality in a homogeneous cohort of south European dialysis patients. Methods: The RISCAVID study was a prospective, observational study in which all patients receiving hemodialysis (HD) in the north-western region of Toscany in June 2004 were enrolled (N=757) and followed up for 24 months. Results: At study entry, only 71 (9%) patients of the entire study cohort exhibited an optimal control of serum phosphorous (Pi), calcium (Ca), calciumX-phosphorous product (CAXPi) and intact parathyroidhormone (iPTH) according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical guidelines. Despite a similar prevalence, the severity of CKD-MBD appeared different to the results reported in the USA. Interestingly, none of the serum biomarkers or number of serum biomarkers within KDOQI targets was independently associated with all-cause and cardiovascular (CV) mortality. Among treatments, Sevelamer was the only drug independently associated with lower all-cause and cardiovascular mortality (p<0.001). Conclusion: The RISCAVID study highlights the difficulty of controlling bone mineral metabolism in HD patients and lends support to the hypothesis that a carefully chosen phosphate binder might impact survival in HD patients. © 2010 Società Italiana di Nefrologia.
Della Nave R.,San Giuseppe Hospital |
Ginestroni A.,University of Florence |
Tessa C.,Versilia Hospital |
Giannelli M.,Pisa Hospital |
And 3 more authors.
American Journal of Neuroradiology | Year: 2010
BACKGROUND AND PURPOSE: HD entails damage of the WM. Our aim was to explore in vivo the regional volume and microstructure of the brain WM in HD and to correlate such findings with clinical status of the patients. MATERIALS AND METHODS: Fifteen HD gene carriers in different clinical stages of the disease and 15 healthy controls were studied with T1-weighted images for VBM and DTI for TBSS. Maps of FA, MD, and λ∥ and λ⊥ were reconstructed. RESULTS: Compared with controls, in addition to neostriatum and cortical GM volume loss, individuals with HD showed volume loss in the genu of the internal capsule and subcortical frontal WM bilaterally, the right splenium of the corpus callosum, and the left corona radiata. TBSS revealed symmetrically decreased FA in the corpus callosum, fornix, external/extreme capsule, inferior fron-to-occipital fasciculus, and inferior longitudinal fasciculus. Areas of increased MD were more extensive and included arciform fibers of the cerebral hemispheres and cerebral peduncles. Increase of the λ∥ and a comparatively more pronounced increase of the λ⊥ underlay the decreased FA of the WM in HD. Areas of WM atrophy, decreased FA, and increased MD correlated with the severity of the motor and cognitive dysfunction, whereas only the areas with increased MD correlated with disease duration. CONCLUSIONS: Microstructural damage accompanies volume decrease of the WM in HD and is correlated with the clinical deficits and disease duration. MR imaging-based measures could be considered as a biomarker of neurodegeneration in HD gene carriers.
Grasso C.,University of Pisa |
Orsini P.,University of Pisa |
Bruschini L.,Pisa Hospital |
Manzoni D.,University of Pisa |
Barresi M.,University of Pisa
Archives Italiennes de Biologie | Year: 2013
Vestibulospinal reflexes can be elicited in humans by low amplitudes direct (galvanic) currents lasting tens of milliseconds and applied across the two mastoids bones, which can be delivered by particular stimulators. This stimulus induces a perception of body sway and a postural response appropriate to counteract the perceived sway. Both the direction of the perceived and of the actual body sway are modulated by the orientation of the head with respect to the body. This modulation depends on the integration of vestibular and neck signals and allows to correctly infer the direction of body sway. In the present study we show that labyrinthine stimulation can be performed also by using train of pulses of 1 msec duration, which can be delivered by virtually all stimulators allowed for human use. Moreover, we developed a simple technique for visualising the time course of the changes in the direction of the postural response, based on the evaluation of the velocity vector of subject's centre of pressure. All together, the results improve the suitability of VS reflex elicitation to clinical practice by indicating stimulation characteristics which can be easily reproduced in both physiological and pathological condition, and by describing a simple, reliable method to analyse the CoP movement elicited by vestibular reflexes.
Giovannetti E.,VU University Amsterdam |
Giovannetti E.,University of Pisa |
Funel N.,Pisa Hospital |
Peters G.J.,VU University Amsterdam |
And 11 more authors.
Cancer Research | Year: 2010
MicroRNA-21 (miR-21) was reported to be overexpressed and contributes to invasion and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether miR-21 expression was associated with the overall survival (OS) of PDAC patients treated with gemcitabine and to provide mechanistic insights for new therapeutic targets. miR-21 expression was evaluated in cells (including 7 PDAC cell lines, 7 primary cultures, fibroblasts, and a normal pancreatic ductal cell line) and tissues (neoplastic specimens from 81 PDAC patients and normal ductal samples) isolated by laser microdissection. The role of miR-21 on the pharmacologic effects of gemcitabine was studied with a specific miR-21 precursor (pre-miR-21). Patients with high miR-21 expression had a significantly shorter OS both in the metastatic and in the adjuvant setting. Multivariate analysis confirmed the prognostic significance of miR-21. miR-21 expression in primary cultures correlated with expression in their respective tissues and with gemcitabine resistance. Pre-miR-21 transfection significantly decreased antiproliferative effects and apoptosis induction by gemcitabine, whereas matrix metalloproteinase (MMP)-2/MMP-9 and vascular endothelial growth factor expression were upregulated. Addition of inhibitors of phosphoinositide 3-kinase and mammalian target of rapamycin resulted in decrease of phospho-Akt and prevented pre-miR-21-induced resistance to the proapoptotic effects of gemcitabine. miR-21 expression correlated with outcome in PDAC patients treated with gemcitabine. Modulation of apoptosis, Akt phosphorylation, and expression of genes involved in invasive behavior may contribute to the role of miR-21 in gemcitabine chemoresistance and to the rational development of new targeted combinations. ©2010 AACR.
Polito E.,University of Siena |
Pichierri P.,University of Siena |
Trivella F.,Pisa Hospital |
Martone G.,University of Siena |
Occhini R.,University of Siena
Journal of AAPOS | Year: 2011
Orbital teratoma in a newborn produces rapid and unilateral proptosis, which, combined with poor eyelid closure, may lead to corneal exposure and vision loss. Early surgical excision of the mass is recommended to preserve visual function. We report a case of an orbital teratoma masquerading as a lymphangioma in 6-month-old girl. The lesion was entirely excised using a transconjunctival approach with good cosmetic and functional results. Copyright © 2011 Published by Elsevier Inc. on behalf of American Association for Pediatric Ophthalmology and Strabismus.