558 research outputs found
L'introspezione tra psicologia del senso comune e psicologia scientifica.
No full textLa questione dello statuto epistemologico dell’introspezione come metodo di indagine è una delle più controverse in psicologia. La maggiore difficoltà a proposito del metodo introspettivo sembra risiedere nel suo ineliminabile carattere soggettivo e ‘in prima persona’, che lo rende difficilmente valutabile in base ai medesimi criteri di validità utilizzati per considerare gli altri metodi di ricerca psicologica quali, per esempio, l’osservazione del comportamento o gli indici neurofisiologici.
Partendo da tali considerazioni, il presente lavoro si propone di affrontare la questione del ruolo dell’introspezione nella ricerca psicologica inserendola all’interno di una problematica più ampia (ma non meno controversa) ovvero quella del rapporto tra psicologia del senso comune e psicologia scientifica. Infatti, se si assume che la soggettività e la prospettiva di prima persona siano a fondamento di tutte le nozioni del senso comune quali credenze, desideri o intenzioni ma non di quelle delle scienze naturali, che mirano a una loro riduzione o addirittura eliminazione, appare evidente come l’introspezione possa avere una rilevanza metodologica solamente nell’ambito una psicologia del senso comune e non nell’ambito di una psicologia che aspira a definirsi scientifica. Per usare la terminologia di Goldman, l’introspezione sembra in grado di fare luce sugli stati consci/soggettivi o macroscopici ma non su quelli inconsci/oggettivi o microscopici (caratterizzati computazionalmente) che sono considerati la reale determinante dei nostri comportamenti e dunque l’oggetto di studio proprio di una psicologia scientifica. Il lavoro si conclude mettendo in discussione la validità di tale proposta e dunque considerando se una psicologia del senso comune rigorosamente definita sia in grado di fornire una spiegazione plausibile del mentale e del comportamento e dunque di esprimere una forma di scientificità alternativa e complementare a quella delle scienze naturali ovvero una scientificità propria delle scienze umane
MULTIMODAL MOLECULAR IMAGING FOR HIF-1ALPHA NON-INVASIVE ASSESSMENT IN A MURINE GLIOMA MODEL
No full textIntroduction: Molecular imaging is an emerging discipline in biomedical research that allows the visual representation, the early characterization and quantification of biological processes at the cellular and subcellular level directly in vivo. Imaging techniques are of great importance since they allow the translation of the data obtained in preclinical models directly to the clinic. In this research, molecular imaging has been applied to the study of a preclinical glioma model, to assess intratumoural hypoxia, as a negative prognostic factor, since it has been correlated to chemo and radio-resistance, tumour progression, increase of invasiveness and to a poor prognosis. For these reasons, hypoxia represents a promising therapeutic target, both in GBM but also in other types of cancer, and an interesting marker able to estimate the prognosis and to predict the therapeutic outcome. In this perspective, the molecular study of hypoxia presented herein was focused mainly on the evaluation of the transcriptional activity of HIF-1α , which is a key factor of the hypoxia process.
Objectives: The main purpose of this project was to study, in a non invasive manner, HIF-1α transcriptional activity as a result of the development and progression of neoplastic disease and after treatment with selective inhibitors and drugs already used in the clinical setting. The first objectives were the characterization and validation of the proposed cell and animal models and the evaluation of HIF-1α activity after treatments of various inhibitors and drugs, to understand its potential role as a prognostic biomarker. The results obtained could be used in the evaluation of the possibility of performing personalized treatments as a result of stratification of individuals depending on HIF-1α activity.
Materials and Methods: The human U251 glioma cell line was used after its appropriatey engineering in order to obtain three models: in the first, U251-HRE, the luciferase reporter gene is under the control of the HRE sequences; in the second, U251-pGL3, the luciferase gene is expressed constitutively, whereas in the third, U251-HRE-mCherry, the mCherry reporter gene is constitutively expressed while the luciferase reporter gene is again under the control of HRE sequences. These lines were first used in vitro for the study of different agents modulating the transcriptional activity of HIF- 1α, whose action has been evaluated primarily by biochemical luciferase assay. Subsequently, the same cells were inoculated orthotopically in nude mice and tumor growth-related events, transcriptional activity of HIF-α, intratumoural hypoxia and therapeutic response, were analyzed using different imaging techniques (BLI, FLI, PET and MRI). The data obtained in vitro and in vivo were also validated ex vivo by histological and immunohistochemical staining.
Results: The in vitro studies have shown that in U251-HRE model,the luciferase activity can be modulated through hypoxia mimetic drugs, such DFX, and it was related to HIF-1α nuclear accumulation In addition, in vitro experiments have allowed to evaluate the contribution of different molecular pathways (involving PI3K/Akt and Ras/MEK/ERK) on HIF-1α activity. As expected, in U251-pGL3 model, the luciferase activity was not modulated. In vivo studies, performed after cell injection in murine models receiving U251-pGL3 cells, showed a linear increase of luciferase activity, proportionally to tumour growth. In contrast, in U251-HRE models a bimodal trend was observed, since it was dependent on hypoxia establishment HIF-1α mediated. These results suggested that this model can be used both in vitro and in vivo for the study of the modulation of HIF-1α activity. Although optical imaging cannot be used in humans, cross- validation of the results obtained with techniques routinely used in the clinic, such as PET and MRI (which gave results comparable and complementary to those provided by optical imaging), allowed to enhance the value of the results obtained in bioluminescence and fluorescence studies due to the possibility to translate these procedures to the clinical setting. The preliminary study conducted with the TMZ has shown, both in vitro and in vivo, that previously to the onset of the cytotoxic effect of the treatment, an early reduction of HIF-1α activity was detectable. The mechanism of action and the significance of this finding, however, have to be explored by further studies.
Conclusions: The U251-HRE model, recapitulating GMB features, could be a reliable model for the study of HIF-1α role in tumour progression. In this context, the optical imaging could be considered a sensitive and versatile technique for the study of the processes related to tumour progression especially those mediated by HIF-1α, but it is limited since it is impossible to translate these data into the clinics. For these reasons, it is extremely important the cross-validation with imaging techniques routinely used in the clinical practice, such as PET and MRI. Moreover, HIF-1α activity could be considered as an early efficacy biomarker after treatment with TMZ, although this crucial process has to be studied in depth
Indagine sierologia riguardante la diffusione del virus Visna/Maedi (MVV) in allevamenti ovini in Italia
No full textSUMMARY - In order to gel a generai indication of thè extent of maedi-visna infection in
dairy and meat sheep flocks in Italy, a wide serological survey covering flocks in several
provinces was carried out in 1998.
Blood samples were obtained through thè courtesy of veterinary surgeons involved in testing
flocks for brucellosis. The recommendation given was to obtain blood samples from thè older
ewes in thè flocks, though on a few occasions blood samples were received from sheep under
two years old. On most farms about 10% of thè flock was bled. However if in thè sample of
ewes tested no serological positive sheep were discovered, then a further group was bled until
at least 75% of thè flock had been sampled or altematively at least one sheep had been
detected with antibodies to MV virus.
On receipt of thè blood samples sera were removed and store at -20°C lili tested. The test
used was thè agar gel immunodiffusion test (AGID). The method adopted was that described
by thè Ministry of Agriculture and Fisheries Central Veterinary Laboratory, Weybridge, UK.
The survey covered flocks in 7 of thè 21 regions in Italy and from 1 ,to 27 farms according to
thè region. Evidence of thè infection with MV virus was found in ali regions and thè number
of farms with antibody positive sheep was from 1 to 20 (44-100%).
A total of 1735 sheep were tested in 7 regions. The number tested on each farm varied from 1
to 100% partly according to thè size of thè flock. Antibodies were found in thè sera of 347
(20%)
sheep
Pregnancy in advanced maternal age: maternal and fetal outcome.
No full textThe objective of this research is to evaluate maternal and fetal outcome of pregnant women over 40 years. The outcome has been evaluated through the following data: age, nationality, number of deliveries, complications of pregnancy, type of delivery, newborn's weight and APGAR index. 201 pregnant women have been recruited. The GDM has been observed in 11 women (5.5%). The antepartum haemorrhage has been observed in 7 women (3.5%). The cesarean section rate was 76% in the Group of primiparae woman and 64% in the Group of multiparae. The incidence of Children LBW (low Birth weight) was 17% in the primiparae and 10% in the multiparare
Role of metformin and AKT axis modulation in the reversion of hypoxia induced TMZ-resistance in glioma cells
No full textHypoxia is a key driver of tumor adaptation promoting tumor progression and resistance to therapy. Hypoxia related pathways might represent attractive targets for the treatment of Glioblastoma Multiforme (GBM), that up to date is characterized by a poor prognosis. Primary aim of this study was to investigate the role of hypoxia and hypoxia-related modifications in the effect of temozolomide (TMZ) given alone or in association with the antidiabetic agent Metformin (MET) or the PI3K/mTOR blocker, BEZ235. The study was conducted in the TMZ responsive U251 and resistant T98 GBM cells. Our results showed that during hypoxia, TMZ plus MET reduced viability of U251 cells affecting also CD133 and CD90 expressing cells. This effect was associated with a reduction of HIF-1α activity, VEGF release and AKT activation. In T98 TMZ-resistant cells, TMZ plus MET exerted similar effects on HIF-1α. However, in this cell line, TMZ plus MET failed to reduce CD133 positive cells and AKT phosphorylation. Nevertheless, the administration of the dual PI3K/mTOR inhibitor BEZ235 potentiated the effect of TMZ plus MET on cell viability, inducing a pro-apoptotic phenotype during hypoxic condition also in T98 cells, suggesting the block of the PI3K/AKT/mTOR pathway as a complementary target to further overcome GBM resistance during hypoxia. In conclusion, we proposed TMZ plus MET as suitable treatment to revert TMZ-resistance also during hypoxia, an effect potentiated by the inhibition of PI3K/mTOR axis
Biological Matrices from Cairina moschata as Non-Destructive Biomonitoring Tools to Study Environmental Quality of Urban and Extra-Urban Areas: A Case Study of Palermo (Sicily, Italy)
No full textBiomonitoring is the qualitative observation and the measurement of biosphere parameters aimed at modelling the environment, evaluating its quality, and studying the effects of alterations on different ecological levels. In this work, trace metal concentrations were assessed using non-destructive biomonitoring tools as blood and feathers of the allochthonous aquatic bird Cairina moschata, collected within two areas of the Palermo metropolitan area, Sicily, differently exposed to air pollution: Parco D’Orleans, in a central urban location, and Monreale, southwest of the city centre. Higher concentrations in both blood and feathers collected in Parco D’ Orleans were found for lead, tin and selenium, but the same was not observed for other metals. The concentrations were not above physiological tolerance in any case. The comparison between blood and feathers allowed to realize that the latter are more useful for biomonitoring analyses, as they are indicative of both external contamination and bioaccumulation. Treatment with nitric acid highlighted that the feathers collected in Parco D’ Orleans had higher metal bioaccumulation than the ones collected in Monreale; however, the treatment needs standardization. The present study confirms that feathers and blood from C. moschata are a convenient and non-destructive sampling tool for metal contamination analysis
Cisplatin plus gemcitabine as adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC): a phase II tolerability study
No full textColor-Doppler imaging and arteriovenous fistula: preoperative evaluation and surveillance
No full textA study on latency in calves by five vaccines against bovine herpesvirus-1 infection
No full textFour bovine herpesvirus-1 (BHV-1) commercial vaccines, three of which (vaccines B, D, E) were modified live vaccines (MLV) and one (vaccine A) identified as a live strain of BHV-1 gE negative, were used for vaccination of calves, using three calves for each vaccine. Three months after vaccination calves were subjected to dexamethasone (DMS) treatment following which virus was recovered from calves inoculated with vaccine B and from those given vaccine D. No virus reactivation was obtained in calves, which received vaccines A or E. The DNA extracted from the two reactivated viruses was subjected to restriction endonuclease analysis. The restriction pattern of the isolate obtained from calves vaccinated with vaccine D differs significantly from that of the original vaccine, whereas the reactivated virus from calves given vaccine B conserved the general pattern of the original vaccine strain. For each reactivated virus in this experiment (B and D) as well as for the isolate obtained from calves vaccinated with a further MLV (vaccine C) in a previous trial, three calves were inoculated. No clinical signs of disease were detected in any of the inoculated calves during the observation period. When the nine calves were exposed 40 days later to challenge infection with virulent BHV-1, they remained healthy and no virus was isolated from their nasal swabbings. These results indicate that some BHV-1 vaccines considered in the project can establish latency in the vaccinated calves, however, the latency does not appear to interfere with the original properties of the vaccines in terms of safety and efficacy
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