Valutazione dell'efficacia di methotrexate e sua influenza sui titoli anticorpali patogenetici nei pazienti affetti da pemfigoide bolloso

Studio osservazionale condotto presso la Dermatologia dell'Università di Bologna atto a valutare l'efficacia di methotrexate e, in particolare, la sua influenza sui titoli degli autoanticorpi patogeni nei pazienti affetti dalla malattia rara Pemfigoide Bolloso

Development of motion analysis protocols based on inertial sensors

The aim of this thesis was to describe the development of motion analysis protocols for applications on upper and lower limb extremities, by using inertial sensors-based systems. Inertial sensors-based systems are relatively recent. Knowledge and development of methods and algorithms for the use of such systems for clinical purposes is therefore limited if compared with stereophotogrammetry. However, their advantages in terms of low cost, portability, small size, are a valid reason to follow this direction. When developing motion analysis protocols based on inertial sensors, attention must be given to several aspects, like the accuracy of inertial sensors-based systems and their reliability. The need to develop specific algorithms/methods and software for using these systems for specific applications, is as much important as the development of motion analysis protocols based on them. For this reason, the goal of the 3-years research project described in this thesis was achieved first of all trying to correctly design the protocols based on inertial sensors, in terms of exploring and developing which features were suitable for the specific application of the protocols. The use of optoelectronic systems was necessary because they provided a gold standard and accurate measurement, which was used as a reference for the validation of the protocols based on inertial sensors. The protocols described in this thesis can be particularly helpful for rehabilitation centers in which the high cost of instrumentation or the limited working areas do not allow the use of stereophotogrammetry. Moreover, many applications requiring upper and lower limb motion analysis to be performed outside the laboratories will benefit from these protocols, for example performing gait analysis along the corridors. Out of the buildings, the condition of steady-state walking or the behavior of the prosthetic devices when encountering slopes or obstacles during walking can also be assessed. The application of inertial sensors on lower limb amputees presents conditions which are challenging for magnetometer-based systems, due to ferromagnetic material commonly adopted for the construction of idraulic components or motors. INAIL Prostheses Centre stimulated and, together with Xsens Technologies B.V. supported the development of additional methods for improving the accuracy of MTx in measuring the 3D kinematics for lower limb prostheses, with the results provided in this thesis. In the author’s opinion, this thesis and the motion analysis protocols based on inertial sensors here described, are a demonstration of how a strict collaboration between the industry, the clinical centers, the research laboratories, can improve the knowledge, exchange know-how, with the common goal to develop new application-oriented systems.

Autoantibodies in patients with psoriasis on anti-TNFalpha therapy

Introduction: Anti-TNF-alfa therapy has been effective in the treatment of patients with refractory psoriasis and psoriasic arthritis. However, the risk of developing autoantibodies in these patients undergoing this therapy is not clear. Objective: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in patients with psoriasis and psoriasic arthritis and, to evaluate the influence of the use of methotrexate on the values of autoantibodies developed during this therapy. Patients and methods: Serum samples from 120 patients, obtained before(baseline) the introduction of anti-TNF-alpha therapy and approximately each 3-6 months during the therapy.O f these 120 patients, 113 were found negative for autoantibodies before starting anti -TNFalpha therapy, 7 were found positive for ANA. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti extractable nuclear antigens antibodies( ENA)(ELISA). RESULTS: Infliximab is associated with the highest occurrence rate of ANA, anti-dsDNA, ENA with approximately 69,2%, 11,5%, 7,6% of patients treated testing positive. In comparison, only 20%, 6,6%, 2,2% of patients treated with Adalimumab, and 19%, 2,3%, 2,3% of patients treated with Etanercept were positive for ANA, Anti-dsDNA, ENA respectively. As regard the seven patients who were positive at baseline, six of them (85.7%) in addition to being remained positive during the therapy they have also increased the autoantibodies ’s titers. Conclusion: our study have shown that Infliximab is associated with the highest rate of autoantibodies. The concomitant treatment with methotrexate did not modify the titers of autoantibodies developed during the therapy anti-TNFalph. The incidence of ANA, anti-dsDNA antibodies did not correlate with development of Lupus-like syndromes. The difference in the frequency of autoantibodies between psoriasis and psoriatic arthritis was not statistically significant (p = 0.867).

Valutazione del coinvolgimento dell'oncogene c-myc e dei trasportatori abc nella farmacoresistenza dell'osteosarcoma ad alto grado

L’insorgenza di fenomeni coinvolti nello sviluppo della farmacoresistenza costituisce al momento la principale causa di mancata risposta al trattamento chemioterapico nell’osteosarcoma. Questo è in parte dovuto ad una sovraespressione di diversi trasportatori ABC nelle cellule tumorali che causano un aumento dell’efflusso extracellulare del chemioterapico e pertanto una ridotta risposta al trattamento farmacologico. L'oncogene C-MYC è coinvolto nella resistenza al metothrexate, alla doxorubicina e al cisplatino ed è un fattore prognostico avverso, se sovraespresso al momento della diagnosi, in pazienti affetti da osteosarcoma. C-MYC è in grado di regolare l'espressione di diversi trasportatori ABC, probabilmente coinvolti nella resistenza ai farmaci nell’osteosarcoma, e questo potrebbe spiegare l’impatto prognostico avverso dell’oncogene in questo tumore. L’espressione genica di C-MYC e di 16 trasportatori ABC, regolati da C-MYC e / o responsabili dell'efflusso di diversi chemioterapici, è stata valutata su due diverse casistiche cliniche e su un pannello di linee cellulari di osteosarcoma umano mediante real-time PCR. L'espressione della proteina è stata valutata per i 9 trasportatori ABC risultati più rilevanti.Infine l'efficacia in vitro di un inibitore, specifico per ABCB1 e ABCC1, è stata valutata su linee cellulari di osteosarcoma. ABCB1 e ABCC1 sono i trasportatori più espressi nelle linee cellulari di osteosarcoma. ABCB1 è sovraespresso al momento della diagnosi in circa il 40-45% dei pazienti affetti da osteosarcoma e si conferma essere un fattore prognostico avverso se sovraespresso al momento della diagnosi. Pertanto ABCB1 diventa il bersaglio di elezione per lo sviluppo di strategie terapeutiche alternative, nel trattamento dell’osteosarcoma, atte al superamento della farmacoresistenza. L’inibizione dell'attività di tale trasportatore causa un aumento della sensibilità al trattamento chemioterapico nelle linee cellulari di osteosarcoma farmacoresistenti, indicando questo approccio come una possibile strategia per superare il problema della mancata risposta al trattamento farmacologico nei pazienti con osteosarcoma che sovraesprimono ABCB1.