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    Dopaminergic modulation of phenotypical and functional characteristics of human T lymphocytes: perspectives for nonconventional immunomodulation.

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    Dopamine (DA) besides its action in the nervous system, plays an important role in immune cells interactions. Emerging role of DA as a regulator of CD4+ T cells physiology is important since dysregulation of different T cell subsets, showing abnormal cell numbers, functions, expression of dopamine receptors (DR) and/or response to DA, could contribute to the onset and development of some immune-related disorders. Thus, directly and indirectly acting dopaminergic therapeutics, currently used in approved clinical indications, could represent an attractive source of non-conventional agents for the modulation of CD4+ T cell functions. The aim of the present work was to develop in vitro methods to investigate the effects of dopaminergic agents, currently used in the pharmacotherapy, on the functional responses of CD4+ T cells, namely: (i) CD4+ T naïve (Tn), T central memory (TCM) and T effector memory (TEM) cells, and their responses to recall antigen (Ag); (ii) CD4+ T regulatory cells (Treg), and their suppressive effects on T effector cells (Teff) and (iii) CD4+ T naïve cells, and their ability to differentiate towards different T helper (Th) lineages (Th1/Th2/Th17). In cultured CD4+ T cells, our results have shown higher expression of DR in apoptotic cells in comparison to viable cells and stimulation-induced DR upregulation of all DR on viable cells. Addition of high concentrations of DA and L-DOPA (100 μM) have shown profound effect on survival of CD4+ T cells. Interestingly, based on preliminary experiments, our ex vivo data have shown trend of proliferating cells expressing DR in higher percentages that still need to be validated in subsequent studies on more subjects. So far, in vitro tested concentrations of dopaminergic agonists have not shown any major effects on proliferation of CD4+ T cells. In addition, through the use of flow cytometric analysis, expression of DR was examined on human: CD4+ naïve T lymphocytes (CD3+CD4+CD45RA+CCR7+), TCM (CD3+CD4+CD45RA-CCR7+), TEM (CD3+CD4+CD45RA-CCR7-), Treg cells (CD4+CD25highCD127low), and also frequency of different Th subsets: Th1 (CD4+CXCR3+CCR4-CCR6-), Th2 (CD4+CXCR3-CCR4+CCR6-), Th17 (CD4+CXCR3-CCR4-CCR6+) and Th1/Th17 (CD4+CXCR3+CCR4-CCR6+) were analysed. DR expression of all five DR was confirmed on each subset, present in a different extension potentially represents an opportunity to develop targeted immunomodulating strategies. Validated and developed in vitro method to test functional response of memory CD4+ T cells towards recall Ag have potential relevance for a wide range of different fields of T cell biology research in health and disease. Additionally, obtained preliminary results have confirmed in vitro experimental conditions likely appropriate to study commitment of naïve CD4+ T cells and factors mimicking specific polarisation routes (Th1/Th2/Th17), which are T subsets important in onset and development of some dopamine-related disorders. Further, in vitro methods have shown CD4+CD25high T cell-dependent inhibition of CD4+ T effector lymphocyte proliferation. Treg cells also suppressed production of IFN-γ and TNF-α from Teff cells. In addition, effects of DA and L-DOPA treatments seems to suppress Treg suppressive capacity in healthy subjects and in the group of Parkinson’s disease (PD) patients who had never been treated (PD-dn), but not in PD patients that were on dopaminergic therapy (PD-dt). Available evidence supports the possibility to repurpose dopaminergic agents as modulators of dopaminergic pathways, shifting the balance towards beneficial outcomes in some pathological conditions, such as PD. Over the last decades, an impressive number of studies in the animal model of immune diseases and in the clinical setting supported this evidence, and strongly required futher testing. The development of therapeutic protocols needs to take into account that DR exists in multiple subtypes and their patterns of expression, and that fuctional relevance differs among immune cells - and may even depend on the functional status (e.g. resting/activated) of specific cells. Proposed in vitro methods examined and characterised the various CD4+ T cell lineages, providing both the conceptual as well as the experimental framework for more in-depth investigation of dopaminergic pathways modulating CD4+ T cell function

    Il proprietario "incolpevole" nei procedimenti di bonifica.

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    This doctoral thesis analyzes – in the light of Constitutional and European principles – the article 253 paragraph 4 of the Environmental Code (d.gls. 152/2006), that, according to the interpretation generally accepted, allows the Public Administration to act against the “innocent” landowner until the amount of the fair value of the site, as it results after the clean-up procedures. Indeed, the Environmental Code obliges the responsible of the land contamination to the reclamation, but it provides for the reclamation the Administration, if the responsible does not arrange it or he is not identified or the landowner or the other person interested does not arrange it. In this case, the public reclamation costs are secured by a special lien (privilegio speciale immobiare) on the land, that is even burdened (onere reale); therefore the “innocent” landowner – although he was not involved in the contamination – have to refund the Administration for the reclamation costs until the amount of the fair value of the site, as it results after the clean-up (art. 253 par. 4). The present work is structured in five chapter: the first three chapters have a reconnaissance nature and concern – respectively – the discipline of the “innocent” landowner, the interpretation of the Courts and the Literature, the “polluter pays” principle; the last two chapters have a constructive nature and concern – respectively – the identification of the “innocent” landowner and the interpretation support of the abovementioned art. 253. The analysis is carried out through two fundamental assumptions, upon which the chosen interpretation is founded. Firstly, it is underlined that the function of environmental responsibility – and, therefore, of the “polluter pays” principle – is, above all, to prevent polluting phenomena, by exercising a deterrent effect on potential behaviors of contamination; to this function is added (but only in a subsidiary way) the function to allocate the incurred costs to one who actually caused the environmental damage. Therefore, for the existence of the responsibility and for the observance of its specific function, it is required the investigation of the existence of the causation between the agent’s conduct and the event raised. Secondly, it is pointed out that the “innocent” landowner is the one who have no causal relationship neither subjective nor objective with the pollution; therefore, he is different from the one who contributed to the contamination with a omissive conduct, that increased the pre-existing situation. Indeed, if, in one case, any causation between the agent’s conduct and the event lacks and, so, there is no responsibility, in the other case, instead, there is a causation regarding to the quid of pollution that the owner has added to pre-existing and, so, regarding to this quid, there is responsibility. In light of the above, it is argued that art. 253 par. 4 should be meant not as a compensation (risarcimento), but as a refund (indennizzo), because it is aimed only to balance the assets involved in the clean-up procedures. After a contamination, in fact, the Administration is obliged to the remediation (imposed by law and previously by primary public need to protect health and environment), that generates a considerable increase in the fair value of the land; as a consequence, there is a profit for the landowner against a loss for the Administration and this economical imbalance is remedied through the lien (onere reale). Therefore, the thesis proposes to interpret the art. 253 as a particular application of the principle of the unjustified enrichment (principio di ingiustificato arricchimento), according to which every economical transfer should have a right cause, under penalty of its repetition. To support the thesis, this work invokes some arguments, regarding the nature and legislative provisions of the lien (onere reale), the Environmental Code, the UE and the international legislation. In conclusion, the thesis considers the main difficulty in the reclamation (i.e. the high costs of the procedures) and, consequently, it hypothesizes a solution. La presente tesi di dottorato analizza, alla luce dei principi costituzionali e comunitari, l’art. 253 comma 4 cod.amb., che, nell’interpretazione generalmente accolta, riconosce all’Amministrazione la facoltà di rivalersi dei costi di bonifica nei confronti del proprietario “incolpevole” fino all’intero ammontare del valore del sito, come risultante all’esito degli interventi. Invero, il d.lgs. 152/2006 obbliga il responsabile della contaminazione alla bonifica del sito e, qualora questi non provveda o non sia individuabile e non provvedano né il proprietario del sito né altri soggetti interessati, prevede che gli interventi di risanamento siano eseguiti d’ufficio dall’ente territorialmente competente. In questo caso, le spese sostenute sono assistite da un privilegio speciale immobiliare sulle aree e sulle stesse viene iscritto un onere reale, con la conseguenza che il proprietario – c.d. “incolpevole”, in quanto la contaminazione non è ascrivibile ad una sua condotta attiva o omissiva – può essere tenuto a rimborsare i costi di risanamento “soltanto nei limiti del valore di mercato del sito determinato a seguito dell’esecuzione degli interventi medesimi” (art. 253 comma 4 cod.amb.). Al fine di indagare la legittimità della norma, si è articolato il lavoro in cinque Capitoli: i primi tre a carattere ricognitivo e concernenti, rispettivamente, la disciplina del proprietario “incolpevole”, le interpretazioni della giurisprudenza e della dottrina sul tema, il principio “chi inquina paga”; gli ultimi due a carattere propositivo e concernenti, rispettivamente, l’individuazione del proprietario “incolpevole” e la rilettura proposta dell’art. 253 cod.amb.. L’analisi si svolge attraverso l’affermazione di due fondamentali assunti, su cui poggia il ragionamento a sostegno della tesi prescelta. In primo luogo, si sottolinea come la funzione della responsabilità ambientale – e, quindi, del “chi inquina paga”, che ne è principio cardine – sia anzitutto quella di prevenire i fenomeni inquinanti, esercitando un effetto deterrente su possibili condotte di contaminazione; a questa funzione si aggiunge (ma solo in una logica sussidiaria) quella di imputazione dei costi di ripristino a chi ha effettivamente causato il danno ambientale. Pertanto, ai fini della sussistenza della responsabilità e del rispetto della sua specifica funzione, è imprescindibile accertare la sussistenza del nesso causale tra la condotta dell’agente e l’evento generato. In secondo luogo, si precisa che il soggetto in questione – ossia il proprietario “incolpevole” – è colui che non presenta alcun legame né soggettivo né oggettivo con l’inquinamento; egli, dunque, si differenzia da colui che ha concorso alla pregressa contaminazione con una condotta omissiva, che ne ha prodotto un aggravamento. Se, infatti, nell’un caso manca qualsiasi nesso eziologico tra condotta e evento e, dunque, non c’è responsabilità, nell’altro caso, invece, il nesso c’è in riferimento a quel quid di inquinamento che il proprietario ha aggiunto al preesistente e, dunque, in riferimento a questo quid c’è responsabilità. Alla luce di tali affermazioni, si sostiene che l’art. 253 comma 4 cod.amb. debba essere inteso non in una logica risarcitoria ma compensativa, essendo finalizzato unicamente a riequilibrare le sfere patrimoniali interessate dal fenomeno di recupero ambientale. In ragione dell’inquinamento, infatti, l’Amministrazione è tenuta al risanamento (impostole dalla legge e ancor prima da esigenze di tutela della salute pubblica e dell’ambiente), il che genera un considerevole aumento di valore del fondo; ne consegue un vantaggio economico per il proprietario a fronte di un dispendio economico pubblico e, a tale squilibrio patrimoniale, viene posto rimedio attraverso l’onere reale. Pertanto, si accoglie la tesi in base alla quale l’art. 253 cod.amb. costituisce un’applicazione particolare del principio dell’ingiustificato arricchimento, in base al quale ogni spostamento patrimoniale deve essere sorretto da una giusta causa, a pena della sua ripetizione. A sostegno di ciò, si invocano una serie di argomentazioni, tratte dalla natura e delle ipotesi legislative di onere reale, dal codice dell’ambiente, dell’ordinamento comunitario e, infine, dal contesto internazionale. In conclusione, tirando le fila del lavoro svolto, si considera quella che è la maggiore difficoltà in materia di bonifica, ossia gli alti costi degli interventi, e, conseguentemente, si ipotizza una proposta di riforma

    Morphological and ‘omics’ analysis of root systems in agronomics plant grown under biochar applications

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    The continued increase of the demand for agricultural crops is responsible of a strong environmental deterioration due to soil fragmentation as well as, to a massive use of fertilizers uses that pollute both water and terrestrial ecosystems. In the future, this demand will growth up more and more. This explain why is crucial to find a new approach and new technologies to achieve greater yields with a lower environmental impact. Biochar is a solid material obtained from a process called pyrolysis characterized by a thermal transformation of biomass at high temperature and in the absence of oxygen. This mineral transformation attributes to biochar a skeletal structure that looks like a carbon sponge, which allows a higher water retention. The addition of biochar to the soil reduces leaching of ammonium compared to untreated soil due to its characteristic sponge structure and recently, it has been observed that also the total nitrates/nitrites, ammonia and nitrogen content and the nitrogen fixation rate are affected. The aim of this work is investigate some morphological and molecular response of plants treated with biochar. For this purpose, two of the most important crop species and one model specie have been tested: 1) Solanum lycopersicum (Cherry tomato of Pachino vr), 2) Vitis vinifera (Chardonnay cv) and 3) Arabidopsis thaliana. Concerning Cherry tomato cultivar, the plant treated with biochar has shown an interesting modification of seedling and fruit traits – especially in the case of fruit quality. In regard to Vitis vinifera, positive effects have been detected in both experiments (pot and field treatments) with biochar, improving the root length in pot experiment while the radial root growth in field experiment. Finally, in Arabidopsis, biochar addition has induced positive effects in all the parameters measured under normal watering regime. In the case of seedlings affected by water stress, the presence of biochar seemed to inhibit strongly the plants growth. Data obtained in this work throw light upon some of the most important aspects of plant nutrition and development. They indicate how those are modified in presence of biochar

    Adaptive changes of the gastrointestinal neuromuscolar function in a mouse model of Catechol-O-Methyl trasferase genetic reduction: implication in the pathogenesis of Irritable Bowel syndrome.

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    Enteric neuronal circuitries display a considerable ability to adapt to a changing microenvironment, which comprises several cellular "players", including neurons, enteric glial cells, smooth muscle cells, interstitial cells of Cajal, immune cells and commensal bacteria (Giaroni et al., 1999). In particular, gut microbiota seems to be directly involved in modulating the development and function of enteric nervous system (ENS), supporting the concept that changes in commensal microbiome composition, induced by infections or antibiotics, can perturb ENS integrity and activity. Neuronal circuitries in the ENS are known to communicate with the Central Nervous System (CNS) via vagal and sympathetic extrinsic pathways: the so called brain-gut axis. Current cutting-edge research suggests that the enteric microbiota, by modifying enteric neuronal circuitries, may communicate with the brain, thus influencing cognitive and behavioural functions. However, early life perturbations of gut microbiota can potentially influence neurodevelopment leading to functional bowel disorders later in life (Ianiro et al., 2016). There is increasing evidence showing that an altered microbiota composition may be related to functional or psychiatric disorders such as irritable bowel syndrome (Bonfrate et al., 2013; Kennedy et al., 2014) and autism (Finegold, 2011; Mayer et al., 2014). Irritable bowel syndrome (IBS) comprises a heterogeneous group of functional lower gastrointestinal tract disorders characterized by abdominal pain or discomfort associated with altered bowel habits and disordered defecation that may be exacerbated by emotional stress. This gut disorder cannot be explained by specific pathophysiologic mechanisms, since it is not associated with any structural finding or biological marker (Mach, 2004). However, the symptoms of IBS are related to combinations of several known physiological determinants such as abnormal motor reactivity, enhanced visceral hypersensitivity, altered mucosal immune and inflammatory functions (which includes changes in bacterial flora), and altered brain-ENS regulation, which is influenced by psychosocial and socio-cultural factors (Drossman, 2006; Ohman and Simren, 2010; Simren et al., 2013). Recently, the association between gut functional disorders, such as IBS, and catechol-O-methyl-transferase (COMT), an enzyme protein which regulates catecholamines levels in mammalian brain (Lundstrom et al., 1995; Mannisto and Kaakkola, 1999) has been proposed. In this perspective, IBS can be described as a disorder of the gut–brain axis (Moloney et al., 2016). The aim of the study was to determine whether a genetic-driven defective COMT activity may affect the structural and functional integrity of murine ENS. Data obtained in the COMTtransgenic mouse model have been compared to those obtained in the gastrointestinal tract of antibiotic treated-mice in order to deplete the microbiota. Data showed that the partial deletion of COMT determined anomalies in the ENS architecture, with a marked increase in protein and mRNA expression of the glial marker S100β. Excitatory cholinergic transmission and inhibitory nitrergic neurotransmission, mainly through iNOS increased expression, led to impaired gut neuromuscular contractility. In addition, an increase of GluN1 glutamatergic subunit expression, affecting visceral hypersensitivity with critical effects on gut function, was also observed. The massive antibiotic treatment determined the same alterations in ENS structure and function observed in the COMT transgenic model. Interestingly, COMT partial genetic deletion induced changes in gut microbioma composition and some commensal intestinal microbial strains underwent drastic changes. In particular, in COMT+/- mice a significant increase of Firmicutes DNA in the ileum and colon and a significant decrease of Bacterioidetes DNA in the ileum were observed with respect to control animals, suggesting that host may affect gut microbial flora arrangement. These data confirmed the importance of studying the interplay between host and microbiota, reflecting alterations in motor and sensitive parameters which resemble some features of functional gastrointestinal disorders, such as Irritable Bowel Syndrome (IBS). In conclusion, this study showed that both COMT genetic deletion as well as dysbiosis may be critical factors involved in the pathogenesis of functional gut disorders, such as IBS

    Improving sustainability of sediment management in Alpine reservoirs: control of sediment flushing operations to mitigate downstream environmental impacts.

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    This thesis focuses on the desiltation of Alpine reservoirs in order to sustain their long-term utilization and restore the functioning of the bottom outlets, minimizing at the same time downstream environmental impacts of sediment removal operations. Different case studies of controlled sediment flushing operations (CSFs) are analysed adopting a multidisciplinary approach. In particular, sediment transport and downstream riverbed alteration, ecological impacts on benthic macroinvertebrates and fish, and performance indicators were investigated. Moreover, the experimental dataset acquired before, during, and after a sediment removal operation was used to carry out and calibrate a one-dimensional sediment transport model of the monitored event. The duration of the CSFs and the average suspended sediment concentration in the outflowing water were constrained, with the specific environmental objective of limiting the downstream fish mortality as predicted by a simple dose/response model. The biomonitoring indicated that this model allowed for a first approximation estimate of the impacts on trout. On the other hand, similar scenarios of sediment removal in terms of duration and average SSC can be identified with analogous predicted impacts on fish but non-negligible differences in flushing efficiency. Therefore, site-specific investigation of environmental impacts may be the key aspect for upgrading the trade-off between economic and environmental needs in planning further operations in the same area

    Catalytic materials for biomass-derived secondary raw materials transformations.

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    The thesis work has been focused on the nanostructuring of heterogeneous catalytic materials for biomass-derived compounds conversion to chemicals and hydrogen. The impact of the nanostructuring is investigated and correlated to the reaction pathways as well. Two biomass-derived model molecules and one by-product of an industrial process were used in as many different catalytic reactions. Acetic acid, as of the most abundant components of the bio-oil derived from the pyrolysis of biomass, and glycerol, as by-product of the emerging biodiesel industry, were used in steam and aqueous phase reforming for hydrogen production. The reduced defectivity of supported Ru nanoparticles, prepared by a novel colloidal method, in the reaction of the steam reforming of acetic acid led in enhanced catalyst stability due to lower coke deposition rates. The addition of Mn as promoter to a Pt-based catalyst was studied and tested in both the steam and aqueous phase reforming reaction of glycerol. The higher hydrogen production shown by the bimetallic catalyst was ascribed to its peculiar acidic surface features. Finally, the direct conversion of cellobiose, a model molecule of the saccharidic-derived biomass, to 5-hydroxymethyl-2-furaldehyde (HMF), which is a platform molecule for the sustainable production of many compounds with high commercial interest, was deeply studied. A series of HCl-treated niobium phosphate catalysts was tested in a recirculating flow reactor. From the complete characterization of the surface acidic features of the catalysts, it appeared that a proper balance of the amount and the nature of the acid sites is fundamental for the catalytic activity toward HMF

    Synthesis, structural characterization and functional properties of metal-organic frameworks based on poly(azolate) ligands.

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    In the firsts two Chapters, a brief introduction on the history of MOFs (Chapter 1), on the features of azolato- and poly(azolato)-based organic linkers and on the properties of fluorine and organofluorine compounds (Chapter 2) is exposed. In Chapter 3 the synthesis of six new non-fluorinated and fluorinated poly(pyrazolato)-, poly(tetrazolato)-, and tetrazolato-derivatives is described. Each linker has been designed for the specific application to be tested. In Chapter 4 the synthesis and characterization of a series of fluorinated and non fluorinated poly(pyrazolato)- poly(tetrazolato)-, and tetrazolato-based MOFs and N-PCPs are presented. The dielectric and CO2 adsorption properties of these new compounds have been investigated. In this context, the well known FMOF-1, has been successfully added to these compounds as a potential low- dielectric material. The synthesis and characterization of the first two Zn(II)-based MOFs ever used as molecular and dipolar rotors is presented in Chapter 5. The investigation on the rotational speed of their aromatic core has been performed with solid state NMR studies. Finally, using four known poly(pyrazolato)-based MOFs, we have tested their catalytic activity in the selective oxidation of hydroxymethylfurfural to diformylfuran. More important, we have disclosed the catalytic mechanism by means of DRIFT and in vacuo FT-IR spectroscopy. All the FT-IR measurements and catalytic results are discussed in Chapter 6

    Colour gradients in cluster ellipticals at z ∼ 1.4: the hidden content of the galaxy central regions

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    The main aim of my Ph.D. thesis is to study how the colour of a sample of cluster ellipticals radially changes and to study its origin in term of variation of the stellar population properties in order to put constraints on the mechanisms of the stellar mass assembly in elliptical galaxies. To this aim, I jointly studied the rest-frame UV-U and UR colour gradients for a sample of 17 elliptical galaxies morphologically selected in the cluster XMMU J2235.3-2557 at z=1.39. The analysis shows that the U-R colour gradients are systematically negative (∼70%) or null (~30%), never positive. On the other hand, the UV-U gradients are systematically positive (∼80%) or null (~20%), never negative. Using stellar population synthesis models, we found that the behavior of the two colour gradients cannot be simultaneously explained by a radial variation of age, metallicity and/or dust. In particular, the negative observed U-R gradients can be produced by an age/metallicity gradient. On the contrary, the positive UV-U gradients cannot be explained with age or metallicity variations and imply an excess of UV emission towards the galaxies’ central regions. This excess calls into question mechanisms able to efficiently produce UV emission without altering the spectrum at longer wavelengths. The data require either steady weak star formation (< 1 M⊙ yr−1) or an He-rich population in the cores of these galaxies in order to simultaneously reproduce both the colour gradients. We have then investigated whether colour gradients depend on the environment, comparing our results with colour gradients in field ellipticals at a comparable redshift present in literature. We found that both cluster and field ellipticals present negative U-R gradients mutually consistent. Conversely to cluster ellipticals, field ellipticals show both positive and negative UV-U gradients. Although the small statistic, this could suggest that the environment could have influenced the evolution of elliptical galaxies. Finally, through the evolution of colour gradients, we investigated how these cluster ellipticals have evolved from z=1.39 to z=0. We found that the evolution of the studied galaxies is consistent with a passive evolution

    Observing neutron stars at the magnetic extremes.

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    The thesis comprises new results on emission phenomena associated with neutron stars (NSs). It describes the long-term X-ray monitoring campaign of an extremely magnetic NS (magnetar) at the Galactic Centre and its extremely slow flux decay, which is challenging most of NS crustal cooling models. It reports on the identification of a source as the slowest NS ever following its recent outburst and also on the first observational demonstration for the existence of complex magnetic field configurations near the surface of X-ray dim isolated NSs. Results of the first systematic study of 19 magnetar outbursts, including searches for (anti-)correlations among different parameters (energetic, maximum flux increase, decay timescale, quiescent flux) are presented. Another chapter is devoted to the modelling of the multi-wavelength emission properties of the transitional pulsar (TMP) PSR J1023+0038 (J1023), i.e. a NS rotating at a period of a few milliseconds in a binary system showing rapid transitions between a bright X-ray pulsar regime powered by the accretion onto the NS surface of matter transferred by the companion star, a radio pulsar regime powered by the energy loss due to the fast rotation of the NS magnetic field and an intermediate accretion regime in which matter accretes only intermittently onto the NS surface. The thesis presents new observational properties of J1023 in the current state and a novel scenario explaining the observed rapid transitions

    Pythagorica medica. Scienza e sapienza nella tradizione pre-ippocratica.

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    The Pythagorean interest in medicine finds its natural collocation among the μαθήματα of the school, holding a privileged role. This wisdom heritage becomes a model for the σοφοί and survives throughout the centuries. Finding out its traces means reconstructing a web of cultural exchanges, particularly lively in the Greek West between the VI and IV century B.C. That’s why this research aims at pointing out some lines of persistency in the wisdom tradition, especially with regard to the field of medicine, through the guiding principles traced by the Pythagorean thought. The enquiry starts from the wisdom and temple medicine in order to highlight its continuity with the Hippocratic tradition. The research path focuses on four archetypal topics which justify the priest skill in medical field and testify the overlap of wisdom and art of healing in ancient times. Birth, Death, Purification and Oath are four anthropological themes: studying them allows to show both the widespread and pervasive nature of the ancient medicine and the role played by the ancient Pythagoreanism. The widespread nature of the documents, especially at the most ancient stage of the history of medicine, imposes to take into account wide historical cultural contexts and face extremely heterogeneous textual typologies which should be integrated with iconographic and archaeological data. That’s why the topic of the research needs to be analised through a multidisciplinary approach

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