The biosynthesis of polyamines has been well established in the embryonic, neonatal, and adult heart, and it displays significant changes that might be correlated to the physiological, biochemical, and ultrastructural changes occurring at the various stages of developing heart. In vitro experiments with cell-free systems have shown that polyamines might positively affect various steps involved in nucleic acid and protein biosynthesis. In accordance with this, the perfusion of isolated hearts with polyamines has been reported to increase the rate of incorporation of ribose, phenylalanine, and acetate into myocardial RNA, protein, and histone, respectively. The possible involvement of cellular polyamines in determining heart cell sensitivity is clearly supported by the fact that inhibition of polyamine accumulation leads to an improved or an impaired responsiveness to cAMP or cGMP-mediated effectors, respectively. Conversely, serum-mediated induction of TAT is completely prevented by blocking polyamine sythesis, thus suggesting that polyamine accumulation is a requirement for the cAMP-independent mechanism of TAT induction.

Contemporary societies increasingly turn to courts to seek answers to individual and collective claims. The political significance that justice has thus acquired is the subject on which we will focus. We start by discussing the method and approach we have chosen to follow. We describe several national cases in the book, based on the work of those social scientists who have focused on the so-called judicialization of politics: that is, the expansion of judicial power. After considering the salient features of this phenomenon, the chapter provides an overview of both the values and institutional settings that have supported this evolution in mature democracies.

Pelo menos desde os anos 90, a corrupção continua sendo listada como uma das principais lacunas que afetam as antigas e as novas democracias europeias. Apesar disso, medir a corrupção política ainda é uma tarefa compli-cada. Nesse cenário, alguns estudos recentes propuseram direcionar a atenção para as ações judiciais para coibir a corrupção, por meio de processo criminal, esclarecendo especificamente as investigações envolvendo políticos de alto nível (Popova e Post 2018; Dallara 2019). Neste artigo, pretendemos apresentar dados sobre processos judiciais de corrupção política na Itália, enfatizando como o número de investigações envolvendo atores políticos parece bastante alto,embora relativamente poucos casos terminem com uma condenação. Alémdisso, pretendemos sugerir alguns fatores explicativos que poderiam explicaressa situação. Entre eles: a relevância da questão no debate político e público;a estrutura de governança do sistema judicial italiano e alguns caracteres dodireito e do processo criminal italiano

Recent decades have witnessed an expansion of judicial power in many countries. How does this phenomenon arise in practice? And what features of the political system are more likely to enhance it? This chapter focuses on the ways in which the judicialization of politics develops – highlighting the different forms that this phenomenon can assume – and then reviews the hypotheses that have been envisaged to explain both its occurrence and its latency.

People's interest in the administration of justice has increased over the years as has the number of scholars engaged in this field. This is hardly surprising, especially if one considers how many countries have experienced an expansion of the judiciary and the magnitude of this evolution. In this concluding chapter we will first discuss briefly the prospects for research, stressing the need to widen the scope of empirical analysis and to study courts within the networks of relationships in which they are embedded. We will then describe the varying assessments of the process of judicialization. Finally, an attempt will be made to take stock of its effects on political systems.

At least since the 1990s, corruption has continued to be listed as one of the major shortcomings affecting old and new European democracies. In spite of that, measuring political corruption is still a tricky task. In this scenario, some recent studies proposed to turn the attention to the judicial actions to curb corruption, through criminal prosecution, shedding light specifically on the investigations involving high-level politicians (Popova and Post 2018; Dallara 2019). In this paper we aim to present data about judicial prosecution of political corruption in Italy, emphasizing how the number of investigations involving political actors seems rather high, although relatively few cases end with a conviction. Moreover, we aim to suggest some explanatory factors that could account for this situation. Among them: the salience of the issue in the political and public debate; the governance structure of the Italian judicial system and some characters of the Italian criminal law and procedure.

If we are to grasp the role justice plays in individual countries, it is necessary to push the analysis beyond the institutional guarantees of independence and consider the organizational context in which courts operate: the judicial system. Relevant aspects include the jurisdiction and its internal dynamics, namely, the kind of disputes that a judge can be asked to settle, and the relationships between lower and upper courts. Furthermore, the channels and the resources available to gain access to justice are of primary importance since they affect the concrete opportunities for individuals and groups to take their cases to court. Finally, public prosecutors must be considered, that is, the institutional actors who patrol access to criminal justice.

Contemporary political systems entrust courts with the task of resolving disputes arising from the application of laws. Judges, who together embody the judiciary, therefore, perform a crucial function in these systems and play a role that is even more important in constitutional democracies. The status of judges – how they are recruited and trained, their career path, and the guarantees they are recognized – is an indispensable element for assessing the ability of judicial systems to fulfill their functions and to have an impact on the political environment. However, judiciaries in democratic regimes differ in several respects. In addition to the traditional variations between common law and civil law, other differences have emerged over time. Legislative reforms recently enacted in Latin Europe have enhanced judicial independence and triggered a process that has gained strong support at the international level.

With a view to understanding the political significance of judicial systems, other elements must now be added. First, the powers that courts exercise when they handle disputes are relevant. In particular, the scope of judges' prerogatives for governing the full sequence of trial events is the key variable. Second, constitutional review of legislation must be considered since it is the most sensitive power with which courts can be entrusted. Finally, the enforcement of judicial rulings also deserves attention; this means drawing a line between outputs and outcomes of the judicial system, that is between decisions and their outcome, if any. This will require a close examination of the institutional devices and conditions that either allow political actors to withstand unwelcome rulings or foster their propensity to comply with them.

The legitimacy of judicial decisions affects their enforcement: sentences regarded as legitimate are more likely to be respected. Normally courts justify their decisions with reference to the law. As we have seen in Chapter 2, the principle of legality is one of the main sources of legitimacy for the judge. However, this role can be construed in a variety of ways. Besides conceptions which emphasize adherence to legal dispositions, some views stress the margins of discretion and autonomy from political institutions that judges enjoy. In these cases, courts are considered as rational actors who may decide based on the objectives they wish to pursue. Although this field is difficult to investigate, the institutional setting of the judiciary sheds some light on the prevalence among its members of one or another role-conception.

Building on the theories considered in the previous chapter, several cases of judicialization "in action" are analyzed (USA, Italy, Germany and India), along with cases in which judicialization has not developed all its potential (UK, Sweden, Japan) and cases that seem to point to a retreat of this phenomenon (Hungary, Poland, Turkey). Finally, the role of courts in non-democratic regimes is also considered.

A posição atual do Ministério Público na engenharia institucional italiana apresenta algumas características que o distinguem dos demais ordenamentos jurídicos nos principais regimes democráticos. Em particular, seguindo o modelo francês introduzido por Napoleão no início do século XIX, as funções do Ministério Público são confi adas ao mesmo corpo de magistrados que desempenha também funções judicantes. A partir da segunda metade do século XX, as garantias de independência da magistratura italiana foram progressivamente fortalecidas, envolvendo nesse processo também os membros do Ministério Público. Assim, após longa evolução, os membros do Ministério Público italiano passaram a gozar das mesmas garantias, autogovernando-se por meio do mesmo órgão, o Consiglio Superiore dalla Magistratura (Csm). O artigo aborda, assim, aspectos históricos e a peculiaridade do modelo italiano, e focaliza especialmente os mecanismos de controle da instituição e as recentes propostas de reforma no atual contexto político da Itália.

Background: α-Mangostin (αMG) is extracted from Garcinia mangostana Linn and exerts antiproliferative activities. Although several researches on αMG were performed using cell monolayers, the in vitro pharmacological effects on 3D cancer models have never been investigated. Aim of the present study was to find new anticancer properties of αMG by evaluating the changes that this compound provokes in multicellular tumour spheroids (MCTSs). Methods: MCTSs were generated from MDA-MB-231 and MCF-7 breast tumour cell lines and then treated with 0.1÷30 μg/ml αMG for 24 and 48 h. MCTS size, density, and cell migration were determined by software elaboration of phase contrast images captured by a digital camera. Cell viability was evaluated by resazurin and acid phosphatase assays, while cell apoptosis was assessed by a fluorescent assay of caspase activity. The distribution of living cells inside MCTSs was shown by live/dead fluorescence staining. Results: A dose-dependent decrease in cell viability was obtained by treating MDA-MB-231 spheroids with αMG for 48 h (IC50 = 0.70-1.25 μg/ml). A significant reduction in spheroid volume, paralleled by its increased compactness, was observed only at concentration of 30 μg/ml, but not with lower doses of αMG. By contrast, αMG in the range of 5-15 μg/ml increased the size of MCTSs due to a parallel reduction in cell aggregation. The same window of concentrations was also able to stimulate cell apoptosis in a dose-dependent manner. Bimodal volumetric effects were also obtained by treating the spheroids generated from the MCF-7 cells with 0.1÷30 μg/ml αMG for 48 h. Finally, doses higher than 5 μg/ml caused a progressive impairment in cell migration from the edge of MDA-MB-231 MCTSs. Conclusion: After exposure at doses of αMG just above IC50, MDA-MB-231 spheroids showed a significant reduction in cell adhesion that did not stimulate cell migration but, on the contrary, blunted cell motility. These findings suggest a novel anticancer feature of αMG that could be taken into consideration to improve conventional drug penetration into the tumour bulk.

Background: α-Mangostin (αMG) is a natural substance that exerts a wide range of antitumor effects. Recently, we described that free αMG was able to dissociate multicellular tumour spheroids (MCTSs) generated from breast carcinoma cells and to reduce their cellular viability and motility. Here, αMG was encapsulated into lipidic nanoparticles (NPs), conjugated or not to a CD44 thioaptamer, and the anticancer action evaluated against MCF-7 breast MCTSs. Methods: NPs containing αMG were formulated with a core of polylactic-co-glycolyc acid. Some of them were decorated with a CD44 thioaptamer using as catalysts 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. Both size and density of MCF-7-derived MCTSs were monitored during 72 h of treatment with NPs carrying 0.1, 0.5 and 1.0 μg/ml final concentrations of αMG. MCTSs were cultured on Matrigel or gelatine to better simulate the extracellular environment. Results: The NPs without thioaptamer and conveying 0.1 μg/ml αMG caused a significant dissociation of the MCTSs grown in gelatine after 24 h of treatment (p < 0.01). The most significant disaggregation of MCTSs was obtained using NPs carrying 0.5 μg/ml αMG (p < 0.01). A similar dissociating effect was observed when MCTSs were cultured in Matrigel under the same conditions for 48 - 72 h. By contrast, only concentrations over 1.0 μg/ml of free αMG were able to provoke a damage to MCTSs, consisting in a substantial reduction in their size (p < 0.05). Since the MCTS dissociation induced by αMG-loaded NPs occurred only in the presence of Matrigel or gelatine, an impairment of cell contacts to collagen fibres was likely responsible of this effect. Finally, the treatment of MCTSs with αMG-loaded NPs that were conjugated to the CD44 thioaptamer caused a similar decrease in density but a lower expansion of the spheroid, suggesting that a significant number of cells were died or arrested in cycle. Conclusion: Very low concentrations of αMG delivered by lipidic NPs are sufficient to provoke a substantial disaggregation of MCF-7 MCTSs that involves cell-to-collagen contacts. Similarly, the treatment of MCTSs with NPs conjugated to a CD44 thioaptamer leads to MCTS dissociation but through a more damaging action that causes also a reduction in cell number.