3 resultados para IL-1-BETA RELEASE

em AMS Tesi di Dottorato - Alm@DL - Università di Bologna


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Research for new biocompatible and easily implantable materials continuously proposes new molecules and new substances with biological, chemical and physical characteristics, that are more and more adapted to aesthetic and reconstructive surgery and to the development of biomedical devices such as cardiovascular prostheses. Two classes of polymeric biomaterials seem to meet better these requirements: “hydrogels” , which includes polyalkylimide (PAI) and polyvinylalcohol (PVA) and “elastomers”, which includes polyurethanes (PUs). The first ones in the last decade have had a great application for soft tissue augmentation, due to their similarity to this tissue for their high water content, elasticity and oxygen permeability (Dini et al., 2005). The second ones, on the contrary, are widely used in cardiovascular applications (catheters, vascular grafts, ventricular assist devices, total artificial hearts) due to their good mechanical properties and hemocompatibility (Zdrahala R.J. and Zdrahala I.J., 1999). In the biocompatibility evaluation of these synthetic polymers, that is important for its potential use in clinical applications, a fundamental aspect is the knowledge of the polymers cytotoxicity and the effect of their interaction with cells, in particular with the cell populations involved in the inflammatory responses, i.e. monocyte/macrophages. In consideration of what above said, the aim of this study is the comprehension of the in vitro effect of PAI, PVA and PU on three cell lines that represent three different stages of macrophagic differentiation: U937 pro-monocytes, THP-1 monocytes and RAW 264.7 macrophages. Cytotoxicity was evaluated by measuring the rate of viability with MTT, Neutral Red and morphological analysis at light microscope in time-course dependent experiments. The influence of these polymers on monocyte/macrophage activation in terms of cells adhesion, monocyte differentiation in macrophages, antigens distribution, aspecific phagocytosis, fluid-phase endocitosis, pro-inflammatory cytokine (TNF-α, IL-1β, IL-6) and nitric oxide (NO) release was evaluated. In conclusion, our studies have indicated that the three different polymeric biomaterials are highly biocompatible, since they scarcely affected viability of U937, THP-1 and RAW 264.7 cells. Moreover, we have found that even though hydrogels and polyurethane influences monocyte/macrophage differentiation (depending on the particular type of cell and polymer), they are immunocompatible since they not induced significantly high cytokine release. For these reasons their clinical applications are strongly encouraged.

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Il lavoro di tesi ha l’obiettivo di dare seguito e profondità alle verifiche già condotte negli anni scorsi da Monticini e Baglioni, da Angelini e da Vento e La Ganga. Nel dettaglio nella serie storica dei tassi scambiati, sul comparto ON, del mercato e-Mid, riscontrano empiricamente che i tassi scambiati nelle prime ore del mattino sono in media superiori rispetto a quelli del pomeriggio. In pratica emerge un costo orario positivo. Il campione è costituito da 196.571 contratti eseguiti tra il 1 gennaio 2007 ed il 31 marzo 2009, sul comparto ON. Le analisi si sono concentrate sull’intensità del reversal patttern, oltre che su base giornaliera anche su base settimanale (day of the week) e su base mensile (month of the year effect). Le medesime analisi sono state condotte sull’ultimo giorno del periodo di mantenimento, e su particolari giorni che hanno scandito la crisi finanziaria. Per osservare la dinamica del reversal pattern prima e durante la crisi, le medesime verifiche sono condotte su tre sub campioni. Il primo considera tutti i contratti dall’inizio e fino all’8 agosto compreso; il secondo da quest’ultimo e fino al 12 settembre 2008 compreso; l’ultimo dal fallimento della Lehman e fino al 31 marzo 2009. I risultati confermano la presenza del reversal, per tutti i giorni e per tutti i mesi. Tuttavia quando il campione è suddiviso, le stime del primo campione, perdono di significatività, in particolare il giovedì ed il mese di febbraio. Sel medesimo periodo di campionamento al fine di verificare se il reversal pattern sia attribuire in parte anche alla liquidità del mercato, si è indagato su tutte le proposte in bid ed in offer, e dei relativi volumi, ovvero sul bid ask spread, il relativo prezzo medio ed i volumi. Anche in questo caso le analisi si sono concentrate oltre che sul campione originario, anche sui tre sub campioni in cui è stato successivamente suddiviso. . Quando infine si analizzano volumi e proposte, si nota innanzitutto che, al mattino, quando i prezzi scambiati sono maggiori il bid ask spread è minimo. Viceversa il pomeriggio quando il BAS è minore. La stessa dinamica si osserva per lo spread effettivo (SE), il quale è pari alla differenza tra prezzo medio delle contrattazioni e prezzo medio delle proposte. Infine i volumi sia delle proposte che delle contrattazioni, sono maggiori al mattino rispetto al pomeriggio e tendono a decrescere con l’intensificarsi della crisi. Inoltre i volumi in bid sono sempre maggiori rispetto a quelli in offer al mattino piuttosto che al pomeriggio.

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Infantile hemangiomas (IHs) are the most common benign neoplastic pathology of childhood; their natural history generally involves three phases: after the onset, which usually occurs in the first weeks of life, there is the proliferation phase where the IH reaches its maximum development and it is followed by the spontaneous involution which leads to the IH regression. The duration and the extent of these phases may vary widely even though in most of the cases the involution process begins around twelve months of life and the regression, complete or partial, is completed around seventh-ninth year of life. The majority of the IHs does not require any treatment. However, 10%-20% is likely to develop serious complications, functional impairments or aesthetic alterations and entail a timely treatment. Although there is no treatment protocol currently shared, therapies usually used in cases with a complication risk consist in: systemic or intralesional steroids as a first choice; interferon α, vincristine and/or bleomicin as second or third choice and/or surgical treatment. Propranolol, a non-selective beta-blocker, has been used for cardiovascular diseases even in childhood for decades. Since 2008 it has been widely used in the IHs treatment, although it is still "off-label". In literature there are hundreds of cases and some clinical studies that show the effectiveness and safety of this drug for this indication. Thanks to a multidisciplinary team (Dermatologists, Cardiologists, Paediatricians, and Radiologists) of S. Orsola-Malpighi Hospital, a clinical study, which has been previously approved by the ethics committee, is carried out in order to evaluate the efficacy and safety of systemic propranolol in the treatment of IHs in paediatric age. At the end of 2012, 78 patients underwent this treatment: the results we have obtained so far show a good efficacy and safety profile in agreement with the data provided by the literature.