IN "POLPO ... SITION" E ALTRI BREVI RACCONTI

Assalito dalla felicità corsi al mare, guardai l’acqua e fui preso da una forza, non mia, non umana che mi trascinò in acqua. Lì venni rapito da fantastiche sensazioni, l’adrenalina salì a mille, vidi un enorme creatura che suscitò in me delle emozioni mai provate prima, si era avvicinata talmente tanto che stava per toccarmi e, appena lo fece, il mio corpo si illuminò magicamente, le mie mani iniziarono pian piano ad assottigliarsi, il mio petto diventava sempre più piccolo e tondo e da lì a poco, ero diventato un polpo

Problematiche di Compatibilità Elettromagnetica: Requisiti per Sistemi Militari

Scopo della presente tesi è quello di fornire una panoramica dei requisiti che un sistema elettronico deve possedere affinché possa essere utilizzato nell’ambiente elettromagnetico militare a cui è destinato senza subire degradi prestazionali. Il riferimento principale è lo Standard MIL-STD-464A

Chronic lymphocytic leukemia cells impair osteoblastogenesis and promote osteoclastogenesis: role of TNF\u3b1, IL-6 and IL-11 cytokines

Bone skeletal alterations are no longer considered a rare event in Chronic Lymphocytic Leukemia (CLL), especially at more advanced stages of the disease. This study is aimed at elucidating the mechanisms underlying this phenomenon. Bone marrow stromal cells, induced to differentiate toward osteoblasts in osteogenic medium, appeared unable to complete their maturation upon co-culture with CLL cells, CLL cells-derived conditioned media (CLL-cm) or CLL-sera (CLL-sr). Inhibition of osteoblast differentiation was documented by decreased levels of RUNX2 and osteocalcin mRNA expression, by increased osteopontin and DKK-1 mRNA levels, and by a marked reduction of mineralized matrix deposition. The addition of neutralizing TNFalpha, IL-11 or anti-IL-6R monoclonal antibodies to these co-cultures resulted into restoration of bone mineralization, indicating the involvement of these cytokines: these findings were further supported by silencing TNFalpha, IL-11 and IL-6 in leukemic cells. We also demonstrated that the addition of CLL-cm to monocytes, previously stimulated with MCSF and RANKL, significantly amplified the formation of large mature osteoclasts as well as their bone resorption activity. Moreover enhanced osteoclastogenesis, induced by CLL-cm, was significantly reduced by treating cultures with the anti-TNFalpha moAb Infliximab; an analogous effect was observed by the use of the BTK inhibitor Ibrutinib. CLL cells, co-cultured with mature osteoclasts, were interestingly protected from apoptosis and upregulated Ki-67. These experimental results parallel the direct correlation between TNFalpha amounts in CLL sera and the degree of compact bone erosion we previously described, further strengthening the indication of a reciprocal influence between leukemic cells expansion and bone structure derangement

Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway

Abstract Skeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone