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Valutazione epidemiologica e terapeutica dei traumi toraco-addominali.
No full textThe Varese's Circolo Hospital is qualified as a second level Emergency and Admittance Department (DEA), that is a structure able to face any traumatic lesions round the clock.
A 118 operations Center is lovated inside this structure.
Trauma assistance management should be guaranteed by the application of shared protocols and by the synergy between the above mentioned structures.
There are no current data about major thoraco-abdominal traumas incidence in the catchment area of Varese.
The aim of the study is the epidemiological evaluation and the knowledge of surgical therapeutic course of patients with traumatic thoraco-abdominal lesions.
One hundred sixty-seven patients with major thoracic and thoraco-abdominal traumas, admitted into Varese Hospital between January 2007 and August 2009, were included in the study
Multiple-welled tunnelling systems in glasses at low temperatures.
No full textThe thesis examines anomalous effects in the physical properties of some multicomponent glasses at low temperatures in the absence and in the presence of a magnetic field.
These anomalous effects can be explained well in terms of a new (anomalous) tunnelling systems (ATS) model. ATS in glasses are provided by the process of partial devitrification of the glassy network due to the presence of network-modifying ions in real glasses. A new probability distribution, inversely proportional to the energy asymmetry, takes into account partial devitrification. The effect of the magnetic field is explained by introducing the Aharonov-Bohm coupling into the Hamiltonian of a single ATS.
The multi-welled ATS together with the standard two-level tunneling systems explain qualitatively, as well as quantitatively and with reasonable parameters, the relative change of the dielectric permittivity and loss at zero and weak magnetic fields for multicomponent glasses such as AlBaSiO (or BAS) and BK7. They also explain the relative change of the dielectric permittivity and heat capacity with temperature T and with alkali concentration x in the mixed (SiO2)1-x(K2O)x glass.
The polarization echo’s theory in glasses has been improved and extended to the case of the independent ATS model describing glasses in a magnetic field. The agreement between theory and experiment is highly satisfactory, given the simplifications used in the theory. The isotope substitution effect on the dipole-echo amplitude also can be explained in a simple way in our model.
The interpretation of the extracted material parameters brings us to confirm the existence of coherent tunneling clusters of N true particles, with a value of N ranging from about 25 at the lowest temperatures, to about 600 at the higher temperatures
Novel mechanisms in the modulation of D-serine cellular concentration: hDAAO-pLG72 interaction
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Zooplankton resting eggs in sediment cores: reconstructing and laboratory testing of Lake Orta's pollution and recovery.
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Six-transmembrane epithelial antigen of the postate (STREAP): a potential target of immunotherapy of prostate cancer.
No full textImmunotherapy has been proposed as a complementary or alternative therapy for the treatment of advanced prostate cancer (PC), one of the leading causes of tumor-related mortality in men. From different approaches that have been tested in recent years, it is now becoming more evident that the choice of the appropriate antigen to target is crucial for the best outcome.
Generally tumor-associated antigens (TAAs) undergo peripheral tolerance during tumor progression, which dampens the efficacy of vaccination protocols. It can be hypothesized that the kinetic and depth of immune tolerance varies depending on the timing and relative expression of the TAA.
These differences may represent a key for successful immunotherapy approaches even in patients with advanced disease.
Aim of my thesis was to investigate the dynamics of CD8+ T cells specific for normal tissue antigens over-expressed during the spontaneous tumor development and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, a primary model of human PC.
We have found that Prostate Stem Cell Antigen (PSCA) and Six-Transmembrane Epithelial Antigen of the Prostate (STEAP), two well known PC-associated antigens, behave differently in term of immunological response when compared with the transgenic Tag IV antigen, which drives oncogenesis in TRAMP mice. While a dendritic cells (DC)-based immunization was able to elicit measurable immune responses for all three antigens in young males affected by mouse prostate intraepithelial neoplasia (mPIN), aged mice affected by PC progressively lost immunity against Tag IV and in part for PSCA, but not against STEAP. The findings correlated with the amount of antigens expressed in the prostate, therefore suggesting that tolerance against this type of TAA follows the same rule of that induced for tissue-associated antigens in peripheral tissues: the more the antigen is expressed the more tolerance is profound.
Finally, a combined therapy of allotransplantation and DC-STEAP vaccination effectively reduced tumor burden in TRAMP mice, underlying how this therapeutic strategy when targeted to a reliable antigen is able to restore cancer immunosurveillance
New microbial hydroxysteroid dehydrogenases and their synthetic application for the selective modification of bile acids.
No full textHydroxysteroid dehydrogenases (HSDHs), mainly obtained from bacterial sources, have been widely employed for the regio- and stereoselective oxidoreduction of the hydroxyl-keto groups of steroids, bile acids and their derivatives. In particular they might be suitable biocatalysts for the industrial synthesis of bile acids derivatives of pharmacological interest such as ursodeoxycholic acid (UDCA; 3α,7β-dihydroxy-5β-cholan-24-oic acid).
Aim of this work was i) to investigate a new enzymatic process for the synthesis of UDCA; ii) to develop new cofactor regeneration systems to be coupled to HSDHs-catalyzed reactions; iii) to clone and overexpress in E. coli new HSDHs suitable for the modification of bile acids up to an industrial level.
Specifically, the preparative-scale HSDHs-catalyzed one-pot enzymatic synthesis of 12-ketoursodeoxycholic acid (3,7-dihydroxy-12-oxo-5-cholanoic acid), a key intermediate for the synthesis of ursodeoxycholic acid, from cholic acid has been investigated. This goal has been achieved by alternating oxidative and reductive steps in a one-pot system and employing HSDHs with different cofactor specificity. To provide the necessary driving force to opposite reactions (i.e., oxidation and reduction) acting concurrently on different sites of the same substrate molecule, suitable cofactor regeneration systems were coupled to these reactions. However, due to a limited cofactor specificity of some of the enzymes used, an undesired reaction equilibrium was established resulting in by-products formation. This problem was overcome by uncoupling the oxidative and reductive biocatalysts (Paper I).
Moreover, a new laccase/mediator system for NAD(P)+ cofactor regeneration in HSDHs-catalyzed oxidations has been developed. This system has been successfully applied in aqueous, buffered reactions (space-time yield of 2.35 g L-1 h-1 ) and in biphasic systems (space-time yields of up to 27.47 g L-1 h-1), demonstrating to be very efficient, to have high stability, to tolerate solvents, and to be simple to employ (Paper II).
Finally, NADPH-dependent 7α- and 7β-hydroxysteroid dehydrogenases (7α-HSDH and 7β-HSDH) from Clostridium absonum were cloned and overexpressed in recombinant form in E. coli. The enzymes were further characterized from a functional and a kinetic point of view, demonstrating that both of them, in suitable bioconversion conditions, could be promising candidates for further applications in the epimerization reaction of bile acids at the C-7 position (Paper III)
