This collection is the most comprehensive account of the Fundamental Law and its underlying principles. The objective is to analyze this constitutional transition from the perspectives of comparative ...constitutional law, legal theory and political philosophy. The authors outline and analyze how the current constitutional changes are altering the basic structure of the Hungarian State. The key concepts of the theoretical inquiry are sociological and normative legitimacy, majoritarian and partnership approach to democracy, procedural and substantive elements of constitutionalism. Changes are also examined in the field of human rights, focusing on the principles of equality, dignity, and civil liberties.
After many waves of democratisation a new type of constitutional transformation has become the focus of scholarly attention. Some researchers claim that the current erosion of constitutionalism can ...be understood better if the phenomenon is compared to the twentieth century dictatorships. Many others argue that what is happening today is a self-destruction of liberal democracy through democratic procedures and under the formal rule of law. This article aims to contribute to the understanding of the new system, and offers another approach. It shows that in a normative sense democracy today is the only legitimate constitutional system. That is why a key attribute of contemporary authoritarianism, a sui generis system between constitutional democracy and dictatorship, is a pretence of democracy. The article suggests that mechanisms of pretence can be identified with the help of constitutional markers, which allow a reliable distinction between constitutional democracy and authoritarianism. Constitutional markers can be revealed on two levels: first, by a systematic account of the constitutional text and practice and second, by exploring the deep structure of the false justification of the system.
Although contemporary populist authoritarians have not entirely abandoned the aims and methods of their ancestors, authoritarianism has been undergoing a reinvention in recent years. Behind a fagade ...of constitutionalism, new authoritarianism claims to abide by democratic principles. Populist authoritarians legitimize themselves through popular elections and maintain the entire set of formal institutions associated with constitutional democracy, using them as both an appearance of representation and a tool of authoritarian imposition.
Hungary's Constitutional Transformation Kovács, Kriszta; Tóth, Gábor Attila
European constitutional law review,
06/2011, Letnik:
7, Številka:
2
Journal Article
Recenzirano
Hungary – Democratic state structure – Two-thirds parliamentary majority – First flurry of constitutional amendments of 2010 – Checks and balances – Media – Ex post facto legislation – Hungarian ...Constitutional Court – Judicial review – Wholesale constitutional review and Basic Law of 2011
Atopic dermatitis (AD) is one of the most common skin diseases, the prevalence of which is especially high among children. Although our understanding about its pathogenesis has substantially grown in ...recent years, and hence, several novel therapeutic targets have been successfully exploited in the management of the disease, we still lack curative treatments for it. Thus, there is an unmet societal demand to identify further details of its pathogenesis to thereby pave the way for novel therapeutic approaches with favorable side effect profiles. It is commonly accepted that dysfunction of the complex cutaneous barrier plays a central role in the development of AD; therefore, the signaling pathways involved in the regulation of this quite complex process are likely to be involved in the pathogenesis of the disease and can provide novel, promising, yet unexplored therapeutic targets. Thus, in the current review, we aim to summarize the available potentially AD-relevant data regarding one such signaling pathway, namely cutaneous opioidergic signaling.
Pruritus or itch generated in the skin is one of the most widespread symptoms associated with various dermatological and systemic (immunological) conditions. Although many details about the molecular ...mechanisms of the development of both acute and chronic itch were uncovered in the last 2 decades, our understanding is still incomplete and the clinical management of pruritic conditions is one of the biggest challenges in daily dermatological practice. Recent research revealed molecular interactions between pruriceptive sensory neurons and surrounding cutaneous cell types including keratinocytes, as well as resident and transient cells of innate and adaptive immunity. Especially in inflammatory conditions, these cutaneous cells can produce various mediators, which can contribute to the excitation of pruriceptive sensory fibers resulting in itch sensation. There also exists significant communication in the opposite direction: sensory neurons can release mediators that maintain an inflamed, pruritic tissue-environment. In this review, we summarize the current knowledge about the sensory transduction of pruritus detailing the local intercellular interactions that generate itch. We especially emphasize the role of various pruritic mediators in the bidirectional crosstalk between cutaneous non-neuronal cells and sensory fibers. We also list various dermatoses and immunological conditions associated with itch, and discuss the potential immune-neuronal interactions promoting the development of pruritus in the particular diseases. These data may unveil putative new targets for antipruritic pharmacological interventions.
Introduction
Extracts and compounds isolated from hemp (Cannabis sativa) are increasingly gaining popularity in the treatment of a number of diseases, with topical formulations for dermatological ...conditions leading the way. Phytocannabinoids such as ( )-cannabidiol, ( )-cannabinol and ( )-Δ9-tetrahydrocannabivarin (CBD, CBN, and THCV, respectively), are present in variable amounts in the plant, and have been shown to have mostly anti-inflammatory effects both in vitro and in vivo, albeit dominantly in murine models. The role of phytocannabinoids in regulating responses of dendritic cells (DCs) remains unclear.
Methods
Our research aimed to investigate the effects of CBD, CBN, and THCV on human DCs differentiated from monocytes (moDCs). moDCs were treated with up to 10 μM of each phytocannabinoid, and their effects on viability, differentiation, and maturation were assessed both alone, and in conjunction with TLR agonists. The effects of CBD on cytokine production, T cell activation and polarization as well as the transcriptome of moDCs was also determined.
Results
Phytocannabinoids did not influence the viability of moDCs up to 10 μM, and only CBD had effects on maturational markers of moDCs, and neither compound influenced LPS-induced activation at 10 μM. Since only CBD had measurable effects on moDCs, in our subsequent experiments we tested the effect only of that pCB. On moDCs differentiated in the presence of CBD subsequent activation by LPS induced a markedly different, much more tolerogenic response. CBD-treated moDCs also produced significantly more interleukin (IL)-6, TNFα and, importantly, IL-10 in response to LPS, which shows a shift toward anti-inflammatory signaling, as well as a more robust secretory response in general. To rule out the possibility that these effects of CBD are specific to TLR4 signaling, we determined the effect of CBD on TLR7/8-induced maturation as well, and saw similar, although less marked responses. CBD-treated moDCs were also less efficient at activating naïve T cells after LPS stimulation, further supporting the tolerogenic effect of this phytocannabinoid on moDCs. Reactome pathway analysis showed an inflammatory response to LPS in moDCs, and to a lesser extent to CBD as well. In contrast CBD-treated moDCs responded to LPS with a shift towards a more tolerogenic phenotype, as IL-10 signaling was the most prominently induced pathway in this group.
Discussion
Our results show that CBD achieves an anti-inflammatory effect on adaptive immune responses only in the presence of an activating stimuli on moDCs by reprogramming cells during long-term treatment, and not through acute, short-term effects.
Fluoxetine is a safe antidepressant with remarkable anti‐inflammatory actions; therefore, we aimed to investigate its effects on immortalized (HaCaT) as well as primary human epidermal keratinocytes ...in a polyinosinic‐polycytidylic acid (p(I:C))‐induced inflammatory model. We found that a non‐cytotoxic concentration (MTT‐assay, CyQUANT‐assay) of fluoxetine significantly suppressed p(I:C)‐induced expression and release of several pro‐inflammatory cytokines (Q‐PCR, cytokine array, ELISA), and it decreased the release of the itch mediator endothelins (ELISA). These effects were not mediated by the inhibition of the NF‐κB or p38 MAPK pathways (western blot), or by the suppression of the p(I:C)‐induced elevation of mitochondrial ROS production (MitoSOX Red labeling). Instead, unbiased activity profiling revealed that they were most likely mediated via the inhibition of the phosphoinositide 3‐kinase (PI3K) pathway. Importantly, the PI3K‐inhibitor GDC0941 fully mimicked the effects of fluoxetine (Q‐PCR, ELISA). Although fluoxetine was able to occupy the binding site of GDC0941 (in silico molecular docking), and exerted direct inhibitory effect on PI3K (cell‐free PI3K activity assay), it exhibited much lower potency and efficacy as compared to GDC0941. Finally, RNA‐Seq analysis revealed that fluoxetine deeply influenced the transcriptional alterations induced by p(I:C)‐treatment, and exerted an overall anti‐inflammatory activity. Collectively, our findings demonstrate that fluoxetine exerts potent anti‐inflammatory effects, and suppresses the release of the endogenous itch mediator endothelins in human keratinocytes, most likely via interfering with the PI3K pathway. Thus, clinical studies are encouraged to explore whether the currently reported beneficial effects translate in vivo following its topical administration in inflammatory and pruritic dermatoses.
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