1,721,140 research outputs found
Acid-Sensing Ion Channels (ASICs): New Targets in Stroke Treatment
No full textIschemic brain damage represents a major source of morbidity and mortality in westernized society and poses a significant financial burden on the health care system. To date, few effective therapies have been realized to treat stroke and promising avenues have not proven clinically useful. Recent evidence, however, suggests that channels, pumps, and ionic exchangers are involved in CNS ischemia and ischemic stroke, but the potential contribution of these channels for curing stroke is far less understood than for many other normal and pathological conditions. New Strategies in Stroke Intervention: Ionic Channels, Pumps, and Transporters analyzes the roles played by targets in stroke development and the potential action of drugs modulating these proteins. This book provides a groundbreaking review of these ionic channels, pumps, and transporters as regulators of neuronal ionic homeostasis, providing a better understanding of ischemic brain disorders and the new pharmacological avenues for a cure. It will be a useful tool for researchers working in this field, and any student interested in the physiological, pathophysiological, and pharmacological features of stroke damag
Analisi morfofunzionali dell'interazione tra fibre minerali micro e nanostrutturate con matrici cellulari
Full text linkExposure to asbestos and asbestos like fibers may induce chronic respiratory diseases. Fibrous erionite, a zeolite, is a strong mutagen, considered more carcinogenic than asbestos fibers in man and rodents, moreover we have found that even fibers such as epsomite can be dangerous. The principal aim of this reseach is to characterize the nature of fibers through a morphological and chemical point of view and then, their interaction with a cell model in vitro by means of ultrastructural analyses.
Different fibers, including minerals already characterized as asbestos fibers (chrysotile, tremolite and amosite), a fibrous silicate not characterized before, an asbeferrite and an erionite one, have been analyzed by means of environmental scanning electron microscopy. Chemical analysis (EDXS Analysis) has been performed on sample aliquots without any preparations under low vacuum conditions (0,80 mbar). Successively, the interaction between fibers and U937 cell membrane has been also investigated. Chemical analysis by inductively coupled plasma-mass spectrometry has been used to determine the trace element composition.
The human monocyte U937 cell line, derived from malignant cells obtained from the pleural effusion of a patient with histiocytic lymphoma, has been chosen to verify the internalization and toxicity of erionite into cells, different fiber concentration have been tested on U937 cells (5, 20 and 100nm) with different times of incubation (24, 36 and 48 hours). Cell response after fiber exposure has been investigated by a transmission electron microscope (TEM). Successively, the interaction between selected fibers (epsomite) and macrophages has been also investigated. The human monocyte U937 cell line has been treated with PMA, a phorbol ester used to convert monocytes into macrophages. Then, cells have been incubated with epsomite fibers for 24 and 48 hours at various dosages and processed for ultrastructural analyses. Cell response after fiber exposure has been investigated by a transmission electron microscope (TEM).
Ultrastructural observations revealed U937 monocytes ability to internalize fibers, which appear both in the cytoplasm and in the nucleus, depending on the concentration and of exposure time. The literature describes a relevant role of macrophages in the antitumor response induced by exposure to asbestos fibers. However, an abnormal activation or an impairment of these cells leads to release of growth factors that can promote tumor growth and development. The potential toxicity of epsomite, firstly characterized through ESEM analysis, has been investigated by means of ultrastructural approaches in cultured macrophages obtained from U937 monocytes. TEM observations revealed cell ability to internalize epsomite fibers, which can be found near to the cell surface, inside of membrane invaginations or of the cytoplasm, where some fibers appear internalized into lysomal granules. Increasing epsomite dose and time to 48h, large fibers can be observed in the cytoplasm, where cannot be correctly digested. This latter event leads to an impairment of lysosomal system, following by mitochondrial damage, and finally cell death. The epsomite exposure in converted U937 macrophages-like induces cytotoxicity which appears to be essential for the pathogenesis of fiber-induced-inflammatory diseases.
The dimensional analysis of the fibers was performed by adapting an official method, used for the calculation of the average diameter of the artificial glass fibers (Rep. Atti n. 211/CSR del 10/11/2016), as the average diameter is a parameter that can be indicative of the danger of the fiber. The adapted protocol was used to determine the mean diameter of the chrysotile, asbeferrite, epsomite and amosite fibers. In the case of erionite, asbeferrite, epsomite and asbestos (chrysotile, tremolite, amosite) we confirmed the expected distribution of the fiber size and of the mean diameter because of their potential carcinogenic risk. Erionite, chrysotile and tremolite are characterized by an extremely fibrous habit, having a diameter about 1 μm and variables lengths, with fibrils of about 0.1 μm diameter. The very small size could favor the deep penetration in the biological system. The morphological and chemical study of asbeferrite, silicate with the presence of iron and magnesium, confirmed the expected distribution of the fiber size and of the mean diameter because of their potential carcinogenic risk. Asbeferrite is characterized by an extremely fibrous habit, having a diameter about 1 μm and variables lengths, with fibrils of about 0.1 μm diameter. The very small size could favor the deep penetration in the biological system, topic that will be the subject of further investigations. The epsomite fibers, a magnesium sulphate with formula MgSO4, have larger diameters (about 4-5 μm), but is characterized by a greater surface reactivity in surface cracking phenomena, and this could be related to the biosolubilization of the fibers in the cellular structures. The formation of fractured crack surfaces could probably be related to hydration reactions with consequent structural variations.
The SEM technique is confirmed as a useful tool for the characterization of fibrous material, the next objectives of the project will be the implementation of measures on mineral and synthetic fibers with possible toxic effects, for the purpose of the drafting of a protocol for the determination of the average diameter of the fibers used in the interaction with the cellular matrix and the deepening of the consequent interactions between fibers and cellular models according to the morphological and chemical characteristics. Furthermore, the SEM analysis allows to obtain a protocol of simple implementation for the dimensional characterization of the fibers, a useful protocol when a first and rapid criterion is needed to establish the potential danger of a mineral fiber not yet characterized
Essays on Equality of opportunity
No full textLa letteratura economica che affianca il principio di eguaglianza delle opportunità suggerisce l’introduzione dei valori libertari e di autonomia nella valutazione del benessere sociale. Questa teoria non si concentra sulla semplice eguaglianza tra i cittadini in termini di reddito, salute, utilità ma valuta l’eguaglianza delle loro opportunità affinché esiti plurimi possano essere raggiunti unicamente sulla base dell’impegno dei singoli individui. Nel primo capitolo ripercorriamo attraverso una breve carrellata le indicazioni provenienti da economisti e filosofi della politica che hanno trattato questo argomento nel corso degli ultimi decenni. Nel secondo capitolo ci occupiamo della misurazione della eguaglianza delle opportunità studiando differenti metodologie che coinvolgono l’indice di Atkinson e i suoi sviluppi in termini di eguaglianza. Il terzo capitolo prosegue invece attraverso una analisi empirica sulla salute. I risultati suggeriscono come le decisioni individuali riguardanti il fumo, considerato come un fattore di responsabilità, influenzino gravemente la salute degli individui rispetto alla loro condizione familiare. Il capitolo 4 studia invece l’interazione tra eguaglianza delle opportunità ed efficienza nel mercato del credito dimostrando come, oltre ad una palese violazione del principio egalitario, esistano anche problematiche di efficienza come surrogato delle dinamiche discriminatorie dovute alle asimmetrie informative.The economic literature on equality of opportunity suggests non-welfarist foundations of social choice introducing the concepts of freedoms and liberties of individuals in the assessment of social welfare. The opportunity egalitarian principle does not focus on equality of outcomes but essentially on equality of means to realize those outcomes, i.e., it places some responsibilities on individuals to decide how much effort to pay in order to exploit the opportunity offered to them. This concept refers to be a part of conventional wisdom and has a long tradition and wide acceptance. On these grounds chapter 1 is devoted to a review of the most recent research on equality of opportunity. Some economists and political philosophers have argued that, in examining distributional questions, instead of focusing on differences in observed incomes or current levels of welfare, it is more appropriate to focus on the choice or opportunity sets that individuals face. Chapter 2 focus on the measurement of the degree of equality of opportunity based on alternative decompositions of the Atkinson index of equality according to welfare theory approach. In chapter 3 we address a measurement in health using data from the British Household Panel Survey (1996-2005). Our results suggest a great incidence of the direct effect of the individual behaviors in terms of lifestyles reducing the indirect contribution of social background. Public health programs are more likely to produce results if targeted on individual responsibility. A different point at issue is tackled in chapter 4 where we introduce the relationship between equality of opportunity and efficiency in the credit market. We show that richer individuals participate more in the credit market even when relatively more averse to effort violating the equality of opportunity principle. Moreover, we find that marginal richer borrowers exert less effort than poorer ones in equilibrium. Empirical evidence in Italy points to a limited impact of policy measures aimed at increasing credit opportunities without targeting accurately the beneficiaries
Multifactorial Decomposition of Inequality: The Case of CAP
No full textThe purpose of this article is to propose a theoretical foundation on the impact of a
transfer scheme on income inequality in the redistribution process among participants
in a related agreement. Our example involves the study of the Common Agricultural Policy implemented by EU Countries. First, we show that ex-post inequality
(after the distribution process) may increase if either initial aggregate income or the
amounts of fiscal contributions are sufficiently high. Second, we characterize a multi-
factorial methodology according to Palestini and Pignataro (2014) to gauge the impact
of redistribution and the effects of different income sources to the inequality profile.
Finally, we propose an exercise where a hypothetical policy is implemented and we
apply the Banzhaf and Shapley values to determine the marginal contributions of each
factor to overall inequality
Learning, proximity and voting: theory and empirical evidence from nuclear referenda
Full text linkThis paper presents novel evidence on the pattern of voting in referenda and develops a spatial learning model that helps explain such behavior. In particular, we shed light on the determinants of voters’ choices over nuclear power using data on two Italian referenda. Exploiting the panel structure of the data, we document that voting against nuclear power increases, whenever the distance from the closest nuclear plant decreases. However, we detect a different voting behavior between municipalities close to existing reactors and those close to proposed ones. A possible explanation is that many citizens hold more precise information on nuclear safety because they have experienced the presence of a reactor in their vicinity for many years. Therefore, we propose a model of voting with endogenous information acquisition interacting both proximity and learning effects, whose results are compatible with the empirical findings. Citizens receive public and private signals and revise their beliefs on the risk of living close to a plant. Such revision process is nested into a spatial voting model establishing conditions for a similar or different voting behavior of the electorate based on the proximity from the reactor
Religion, Intellectual Property, and Innovation
No full textThis chapter discusses the consequences of informal intellectual property (IP) protection through religious rules on innovation. As religiosity is not necessarily accompanied by high levels of morality, the lack of formal IP institutions can be detrimental for technological progress. This fallacy is best visible in the case of Islam, which incorporates the protection of IP in its doctrine. Islamic societies are characterized by weak IP protection regimes, high rates of piracy, and low levels of innovation. The legal enforcement of IP rights is hence beneficial in the absence of trust in the society and cannot be substituted by religious beliefs
Disuguaglianze e Istruzione in Italia. Dalla scuola primaria all'Università
No full textIl volume propone una serie di analisi che spiegano come le disuguaglianze e l’istruzione siano strettamente legate tra loro. Gli autori mostrano come l’Italia sia lontana dalla costituzione di una società in cui tutti i cittadini abbiano le stesse opportunità. Da almeno una generazione l’istruzione è riconosciuta in tutto il mondo come un fattore chiave dello sviluppo economico e motore della scala mobile sociale. Nella corsa all’accumulazione di conoscenza e competenze, l’Italia è attualmente in ritardo. Le classifiche mondiali inseriscono il nostro paese tra gli ultimi posti per mobilità sociale osservando come negli ultimi due decenni la presenza di una perdurante stagnazione dell’economia abbia contribuito all’inasprimento delle disuguaglianze. Gli effetti sociali e politici sono sotto gli occhi di tutti; eppure, una via per uscirne, almeno per le future generazioni, ci sarebbe. Dotarsi degli stessi strumenti di cui si sono dotate le economie che ci hanno sopravanzato: un forte sistema educativo. Farlo, però, non è una strada semplice: richiede volontà politica, coesione sociale e risorse economiche, caratteristiche storicamente carenti ma di cui il nostro paese potrebbe dotarsi con delle scelte politiche ben precise
Editorial: Mechanisms of Innate Neuroprotection
Full text linkAs clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain's own endogenous strategies for neuroprotection. Two endogenous mechanisms have been recently characterized, ischemic preconditioning and ischemic postconditioning. In the present topic newly characterized mechanisms involved in preconditioning- and postconditioning- neuroprotection will be discussed. The understanding of the mechanisms involved in the neuroprotective pathways induced by preconditioning and postconditioning will be clinically relevant for identifying new druggable target for neurodegenerative disorder therapy. Furthermore, the importance of these neuroprotective strategies resides in that it might be easily translatable into clinical practice. Therefore, the data presented here will highlight the capacity of ischemic preconditioning and postconditioning to be of benefit to humans
Farmaci Antimicotici
No full textLo scopo principale degli autori del presente trattato è stato quello di correlare le conoscenze sempre più approfondite sull’azione molecolare dei farmaci con gli effetti farmacologici esercitati nell’uomo e che costituiscono i presupposti razionali della terapia medica. Uno spazio adeguato è stato inoltre riservato alla trattazione degli aspetti farmacocinetici clinici, delle reazioni avverse e delle interazioni tra i farmaci, che rappresentano un aspetto in continuo divenire e che sono spesso alla base di eventi avversi clinicamente rilevanti. L’ intento del testo è stato quello di fornire un’informazione la più completa possibile con l’inserimento nella trattazione di argomenti che hanno assunto negli ultimi anni particolare rilevanza nel campo delle possibili prospettive terapeutiche più moderne. Nel trattato sono presenti infatti capitoli innovativi quali quello sui Farmaci Biotecnologici a bersaglio definito, sulla Farmacogenetica e sulla Terapia Genica. Completano la trattazione argomenti inerenti gli aspetti socio-sanitari , economici e normativi della Farmacologia contenuti nei capitoli sulla Sperimentazione Clinica dei Farmaci, sulla Farmacoeconomia e sulla Farmacologia del Doping. Infine, in considerazione del largo uso che si fa dei prodotti di origine vegetale , si è ritenuto utile affrontare tale problematica nel capitolo Principi di fitoterapia nella pratica clinica
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