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Anticorpi anti nucleari e cellule tumorali circolanti nello studio dell'epatocarcinoma
Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and occurs, in most cases, in patients with chronic liver disease (70-90% of HCC cases), presenting itself in a form multifocal at diagnosis in 75% of cases.
The incidence of primary liver cancer is related primarily to the spread of hepatitis B and C, which has increased between 1950 and 1980 in developed countries. HCC is the most common type of liver cancer worldwide, with a prevalence below that of hepatitis B and C. The incidence is higher in Asia and in sub-Saharan countries, while it is relatively less common in Europe and North America. At European countries where there are the most cases, they are those of the Mediterranean, including Italy. The onset of HCC is usually detected at a distance of 20 to 30 years from the beginning of liver damage and the average age of onset is 60-65 years. Patients with cirrhosis have a higher risk of developing HCC: 90-95% of patients with HCC have liver disease or cirrhosis of the base, but are also recorded cases of non-cirrhotic liver of HCC.
The risk factors for the onset of hepatic cancer are to be sought in pre-existing diseases of the liver such as: cirrhosis, chronic infection with hepatitis B virus (HBV) and hepatitis C (HCV), alcohol abuse and cigarette smoking, obesity (fatty liver) and aflatoxins.
Several works in the literature reveal that antinuclear antibodies (ANA), first level test used in the diagnosis of systemic autoimmune disorders (MAIS), may be positive in patients with cancer but, do not manifest symptoms that match the MAIS.
In the peripheral blood of some patients with cancer is possible found Circulating Tumor Cells (CTCs), particularly those with metastatic disease. The clinical impact of this phenomenon has long been debated. CTCs have been measured in patients with cancer to analyse metastatic mechanisms or in the hope of developing clinical applications for diagnosis and therapy.
Aim: The purpose of this study are essentially two:
1) to detect anti – nuclear antibodies atypical (not commonly associated with the MAIS) as possible tumor markers being HCC .
2) the HCC having a malignant tumor metastases can give. For this reason it was decided to look for the presence of circulating tumor cells in patients with hepatocellular carcinoma , so as to highlight possible parameters that give more information on the state of the disease and especially on its evolution.
Methods: In this work we were enrolled 75 patients diagnosed with hepatocellular carcinoma, some of them were hospitalized at the departments of Internal Medicine and Pathology, University of Sassari others were outpatients , and compared with 19 healthy controls. These patients have been tested in the laboratory for research of the bands " atypical”. Another 15 patients with HCC before diagnosis of non metastatic and untreated were included in the study for the detection of circulating tumor cells and compared with 12 healthy controls. The antibodies anti nucleus of 75 patients with HCC was performed by indirect immunofluorescence (IFI). Of these 75 patients 65 were tested for the detection of protein bands "atypical" by Western Blot (WB). The detection of circulating tumor cells has instead been performed by flow cytometry.
Results: The results show positive for ANA detection of 52% with a prevalence of males than females. The panel fluoroscopic most represented is homogeneous followed by granular and nucleolar. The analysis of the WB show that 63% of the patients tested positive for this test it is 63.3% and show the presence of protein bands "atypical". Those are statistically significant: 104 kDa, 54.7 kDa, 37.7 kDa and 53 kDa. “Atipycal” band of 53 kDa was not taken into account because was present in healthy controls. The flow cytometry put in evidence the presence of a high number of CTC in the 15 patients with non-metastatic HCC and not treated with any type of therapy.
Conclusions: the detection of ANA in patients with hepatocellular carcinoma showed no additional information that was not already present in literature. These ones fact confirms that the ANA are present in this tumor especially in males. Unlike the WB analysis they were identified 3 "atypical" band protein present in patients with hepatocellular carcinoma: 104 kDa, 37.7 kDa and 54.7 kDa. These bands have not been described in terms of research literature yet. For the research of CTC has been possible to distinguish them from other cell populations using specific markers labeled with different fluorophore: CD 45, CD 34, CD 105 and EpCAM. In patients studied was found a high concentration of CTC. Inside the group of the patients positive for the presence of CTCs, some patients show a higher number of these. On the basis of clinical information it is not possible yet describe why some of them have a higher number of CTC
Il Sulcis Arcaico tra Nuragici e Fenici: testimonianze di cultura materiale dal Nuraghe Sirai
The present research aims to study the material culture of Nuragic tradition recovered in association with Phoenician artifacts in already excavated, studied and published archaeological sites, dating to the VIII, VII and VI century BC and located in the Sulcis area (S-W Sardinia). The aim of the research is to understand the cultural and chronological contexts through the scrutiny of previous data and new data deriving from the Vano A and Vano B and some stratigraphic units recorded during the 2012 excavation campaign in the fortification area of the Nuraghe Sirai.
The analysis is therefore oriented towards understanding the colonial encounter dynamics, where the Phoenician counterpart appears a summoning element for the Nuragic populations.
The main objective, mostly reached, has been to create a state of the art compendium on the topic placed side by side with new unpublished data on the ceramic artifacts from within Phoenician towns in archaeological contexts chronologically situated between the VIII-VI centuries BC. Also, the goal was to analyse certain aspects of a simultaneous ceramic production, provisionally defined hybrid, which escapes a clear classification on the basis of ethnic characteristics but shows peculiarities possibly concerning a new local facies of the Ferro II period.
The difficult chronological attribution for some Nuragic artifacts is determined both by the absence of comparative material culture in the published corpus and by the existence of the ceramic production defined, for methodological purposes and by various scholars, hybrid
I Pressoi litici fra classificazione tipologica e indagine sperimentale
The stone presses constitute a fundamental element of the production process and they are of significant interest due to their historical and archaeological value.
Those artifacts, being considered less valuable than others, have enjoyed relative anonymity on the Island. Furthermore, those we are in possession of are of doubtful and mysterious origin and it is difficult to interpret their typology and age.
The aim of this research project is to clarify the topic through the establishment of a stone presses’ sample organised by type and function. This is to be achieved by employing experimental archaeology, etnoarchaeology and the multi-disciplinary archaeology of line production as approached by the "Archeologia dei Paesaggi".
Of those artifacts concerned with the production of wine, the millstones, 103 fixed rural wineries have been found: 12 within the Guilcer area and 91 within the Barigadu area. This is in addition to 53 movable containers connected to at least other 30 wineries.
The results of this research also considerably expand the knowledge and understanding of the methods of oil production in the ancient times.
The existence of methods for oil productions can be proved by the presence of the so called arae. Those are basis made of stone necessary to operate lever presses.
The discovery of over 50 arae indicates a high production for the local market.
Having analysed the evidence discovered, it is appropriate to assume that production was widespread in those areas for a long period of time, namely from the Nuragic period to the late Middle Ages
Riflessioni sulla localizzazione della battaglia di Zama
Analisi delle ipotesi sulla localizzazione della Battaglia di Zama (18 ottobre 202 a.C.)
Type 1 Diabetes at-risk children highly recognize <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> epitopes homologous to human Znt8 and Proinsulin
Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations. Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). A higher prevalence was detected for MAP/ZnT8 pairs (62,96% T1D vs. 7,14% HCs; p < 0.0001) compared to MAP/PI epitopes (22,22% T1D vs. 9,52% HCs) and decreasing trends were observed upon time-point analyses for most peptides. Similarly, classical ZnT8 Abs and GADA decreased in a time-dependent manner, whereas IAA titers increased by 12%. Responses in 0–9 year-old children were stronger than in 10–18 age group (75% vs. 69,1%; p < 0.04). Younger age, female sex and concomitant autoimmune disorders contributed to a stronger seroreactivity suggesting a possible implication of MAP in multiple autoimmune syndrome. Cross-reactivity of the homologous epitopes was reflected by a high correlation coefficient (r2 > 0.8) and a pairwise overlap of positivity (>83% for MAP/ZnT8)
Inhibition of an erythrocyte tyrosine kinase with imatinib prevents <i>Plasmodium falciparum</i> egress and terminates parasitemia
With half of the world’s population at risk for malaria infection and with drug resistance on the rise, the search for mutation-resistant therapies has intensified. We report here a therapy for Plasmodium falciparum malaria that acts by inhibiting the phosphorylation of erythrocyte membrane band 3 by an erythrocyte tyrosine kinase. Because tyrosine phosphorylation of band 3 causes a destabilization of the erythrocyte membrane required for parasite egress, inhibition of the erythrocyte tyrosine kinase leads to parasite entrapment and termination of the infection. Moreover, because one of the kinase inhibitors to demonstrate antimalarial activity is imatinib, i.e. an FDA-approved drug authorized for use in children, translation of the therapy into the clinic will be facilitated. At a time when drug resistant strains of P. falciparum are emerging, a strategy that targets a host enzyme that cannot be mutated by the parasite should constitute a therapeutic mechanism that will retard evolution of resistance
Arginines plasma concentration and oxidative stress in mild to moderate COPD
Background: Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress.
Methods: Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls.
Results: TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25–0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27–13.05; p = 0.02) were independently associated with COPD severity.
Conclusion: COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability
Correlati osteoarticolari e vascolari dell'iperuricemia asintomatica: studio ecografico
Aim: Hyperuricemia is the most important risk factor for the development of gout. Despite this strong association, the majority of patients with hyperuricemia do not develop gout. We investigate the musculoskeletal and vascular ultrasonographic changes in patients with asymptomatic hyperuricaemia.
Methods: Ninety-three hyperuricemic asymptomatic patients with a sustained serum urate concentration equal to or above 7.0 mg/dl documented at least twice in the last 2 years and 93 sex- and age-matched controls were prospectively recruited. A standardised ultrasonography assay was performed to evaluate aggregates, double contourn sign, tendon calcification, erosion, tophy. Furthermore common carotid artery (CCA)-IMT was assessed with automated radiofrequency-based US.
Results: Hyperechoic enhancement of the superficial margin of the hyaline cartilage (double contour sign) and hyperechoic cloudy areas was found in 13% and 11% of the first MTPJs from hyperuricemic individuals, in contrast to none in the control group (P < 0.0001). Similar results were found on the femoral cartilage (10% and 11% versus 0; P < 0.0001). Quadricipital and patellar calcification (13,4% and 9,7 versus 3,4 and 4,3%; P = 0.01) as well as knee (11,3% versus 0%; P = 0.0001) were more frequent in hyperuricemic than in normouricemic individuals. Tendinous tophi and erosion were found in 12 and 15 hyperuricemic individuals respectively but in none of the normouricemic subjects (P = 0.003). The mean CCA-IMT was significantly greater in hyperuricemic patients than in controls [843.29 vs 821.12 ; P = 0.035]
Conclusion: These data demonstrate that morphostructural changes suggestive of gouty arthritis induced by chronic hyperuricemia frequently occur in asymptomatic individuals. Moreover radiofrequency-based measurement of CCA-IMT is greater in hyperuricemic patients as compared with controls
Analyzing the genetic variation of dairy sarda and spanish meat ovine breeds
The aims of this thesis were to investigate if variation at regulatory sites of the milk protein genes is
associated with traits of economic interest in dairy Sarda sheep, as well as the genetic
characterization of Spanish meat ovine breeds. Seven hundred and sixty Sarda sheep were
genotyped with a multiplex TaqMan® assay of 29 SNPs found by us in the four casein genes and
three previously reported SNPs in the LALBA and BLG genes. A high level of polymorphism (1
SNP every 200bp) was revealed and significant associations between CSN1S2 and CSN3 genotypes
and milk protein and casein contents, while CSN1S1 and CSN2 genotypes were significantly
associated with curd firming time. A total of 140 individuals belonging to the Xisqueta, Ripollesa,
Segureña, Gallega, Roja Mallorquina and Canaria de Pelo breeds were genotyped with the Infinium
50K Ovine SNP BeadChip (Illumina). This dataset was merged with 50K genotypes of other five
Spanish breeds (Churra, Ojalada, Castellana, Latxa and Rasa Aragonesa). Population genetics
analyses revealed that Canaria de Pelo, Roja Mallorquina, Latxa and Churra were clearly
differentiated populations. We performed a second experiment aiming to estimate the amount of
shared vs breed-specific variation in five Spanish breeds through a RNA-seq approach. Our results
showed a similar amount of shared vs pool-specific variants. Moreover, the number of pool-specific
SNPs in Canaria de Pelo and Xisqueta was 2-5 fold higher than in the others breeds
Il Capitale sociale nelle associazioni di volontariato in Sardegna
The idea of the research is based on the analysis of the social capital, its meaning, and more precisely its rule in the voluntary organizations. In this regard the research wants to investigate the role that the partecipation in voluntary organization has in terms of creation of different forms of social capital for the stakeolders involved.
The voluntary organizations would have influence in a significant way on the opportunities of economical development of the territory, increasing its share capital level.
The research wants to study if the no profit system utilizes the existence of a strong social capital for its own projects, in this way strengthening it and accumulating it for the benefits of the capital market itself.
One of the most important aspects of the research is that the concentration of the social capital of the volunteers doesn't necessarily mean that the effect of the share capital reflects exclusively on the volunteers, main feature of this social capital is actually the externality they produce as economy.
Secondly the study wants to understand the economical effects that the social capital, developed by the members of the associations, could have on individual and collective level. Particularly, the research will focus on the effects that relations and skills developed in the Associations could ease the success in the research of a job for the unemployed subjects or to facilitate the occupational improvements