Ki alkotja ma a jogot? – avagy a multinacionális cégek, a pénzvilág és a piac domináns szervezeteinek szerepe a jogalkotásban

A jog, amelynek kezdetei a történelem korai szakaszára nyúlnak vissza szorosan összefügg a közösségi szerveződéssel és az állam létrejöttével. A jogalkotás a kezdetektől az állam feladata és privilégiuma volt. Mára mindez megváltozott. Az állam, bár szeretné, ha így lenne, már nem a jog kizárólagos alkotója. Olyan „versenytársai” lettek ezen a területen, mint a multinacionális cégek vagy a pénzvilág és a piac domináns szervezetei, szereplői. Milyen változásokkal jár mindez? Ezt vizsgáljuk tanulmányunkban néhány kiragadott példa kapcsán. | The law, which dates to an early stage in history, is closely linked to the organization of the community and the creation of the state. Legislation has been a task and a privilege of the state from the beginning. Today, all that has changed. The state, although it wants it to be so, is no longer the sole creator of law. They have become “competitors” in this field, such as multinational companies or dominant organizations and players in the financial world and the market. What changes does it all bring? We examine this in our study in relation to some snatched examples

The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary

Fingolimod was approved and reimbursed by the healthcare provider in Hungary for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS) in 2012. The present study aimed to assess the effectiveness, safety profile, and persistence to fingolimod in a real-life setting in Hungary in RRMS patients who were either therapy naïve before enrollment or have changed to fingolimod from another disease-modifying therapy (DMT) for any reason.This cross-sectional, observational study with prospective data collection was performed nationwide at 21 sites across Hungary. To avoid selection bias, sites were asked to document eligible patients in consecutive chronological order. Demographic, clinical, safety and efficacy data were analysed for up to 5 years from 570 consenting adult patients with RRMS who had received treatment with fingolimod for at least one year.69.6% of patients remained free from relapses for the whole study duration; in the first year, 85.1% of patients did not experience a relapse, which rose to 94.6% seen in the 5th year. Compared to baseline at study end, 28.2% had higher, and 9.1% had lower, meanwhile, 62.7% of the patients had stable EDSS scores. Overall, the annualized relapse rate decreased from 0.804 observed at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (77.0%, 82.1%, 85.2%, 89.7%, and 89.0% relative reduction, respectively) after 1, 2, 3, 4, and 5 years of treatment. The greatest reduction rate was seen in the group of therapy naïve patients. Treatment persistence on fingolimod after 60 months was 73.4%.In this nationwide Hungarian cohort, most patients under fingolimod treatment were free from relapses and disability progression. In addition, fingolimod has proven to be a well-tolerated DMT that has sustained its manageable safety profile, high efficacy, and positive benefit/risk ratio for up to 5 years in a real-life setting

Rôle des variants de la fibronectine autocrine dans les cellules endothéliales

Les variants de la fibronectine cellulaire (FNc) contenant des motifs répétés de type III, incluant les extra-domaines A et B, sont les principaux constituants de la matrice extracellulaire supportant les vaisseaux sanguins néoformés au cours du développement et de l angiogénese. Leur expression est régulée par des stimuli angiogéniques et leur assemblage en réseau fibrillaire est conduit par des récepteurs de la famille des intégrines a5b1 et de leurs partenaires cytoplasmiques tels que la protéine ILK (integrin-linked kinase) et la tensine 1. Mon travail de thèse a consisté à étudier le rôle des différents variants de la FNc dans des cellules endothéliales aortiques de bœuf en culture, en utilisant l ARN interférence pour cibler spécifiquement les isoformes. Ces résultats montrent que les celulles défficientes en FNc sont incapables d assembler une matrice subendotheliale indiquant que la fibrillogénese de la fibronectine au sein des cellules endothéliale est un processus cellulaire autonome. L extinction spécifique de l expression des différents variants de la FNc altère la fonction des intégrines et impacte sur la signalisation cellulaire en aval qui régule l organisation du cytosquelette, la motilité cellulaire, la prolifération et la morphogénese des capillaires sur une matrice de membrane basal. L inhibition de l expression de la FNc entraîne une relocalisation de ILK et tensine 1 des adhésions fibrillaires contenant les intégrines a5b1 vers des structures adhésives contenant les intégrines avb3. De plus, cette modification d expression des intégrines est associée à une perturbation des jonctions adhérentes dépendante de Src. Ce travail révèle donc un nouveau rôle de la fibronectine autocrine dans l assemblage de la matrice subendothéliale et l intégrité des jonctions adhérentes, permettant ainsi un strict contrôle à la fois spatial et temporel de la plasticité endothéliale au cours du remodelage des vaisseaux sanguins nécessaire à l angiogénese.Cellular fibronectin (cFN) variants containing extra FN Type III repeats, including Extra Domains B and A, are major constituents of the extracellular matrix (ECM) surrounding newly forming blood vessels during development and angiogenesis. Their expression is regulated by angiogenic stimuli, and their assembly into fibrillar networks is driven by a5b1 integrin and cytoplasmic partners such as Integrin Linked Kinase (ILK) and tensin1. During my thesis J examined the role and potential functional redundancy of the different cFN variants in cultured bovine aortic endothelial (BAE) cells, using isoform-selective RNA interference. The results show that cFN-depleted cultures fail to assemble a subendothelial matrix indicating that FN fibrillogenesis is a cell autonomous process in endothelial cells in which basal secretion of cFN is coupled to integrin-dependent assembly. Isoform-specific cFN silencing alters integrin usage and impacts on downstream signalling events that regulate cytoskeletal organization, cell motility, proliferation and capillary morphogenesis on a basement membrane matrix. Silencing of cFN causes a shift of ILK and tensin 1 from a5b1-containing fibrillar adhesions to avb3-based adhesive structures. This integrin switch is accompanied by a Src-regulated disruption of adherens junctions. Altogether, these results highlight a novel role for autocrine FN in subendothelial matrix assembly and junctional integrity thus providing a spatially and temporally restricted control of endothelial plasticity during angiogenic blood Bessel remodelling.NICE-BU Sciences (060882101) / SudocSudocFranceF

Angiogenic Sprouting Requires the Fine Tuning of Endothelial Cell Cohesion by the Raf-1/Rok-α Complex

Sprouting angiogenesis, crucial for the development of new blood vessels, is a prime example of collective migration in which endothelial cells migrate as a group joined via cadherin-containing adherens junctions (AJ). The actomyosin apparatus is connected to AJ and generates contractile forces, which, depending on their strength and duration, increase or decrease cell cohesion. Thus, appropriate spatiotemporal control of junctional myosin is critical, but the mechanisms underlying it are incompletely understood. We show that Raf-1 is an essential component of this regulatory network and that its ablation impairs endothelial cell cohesion, sprouting, and tumor-induced angiogenesis. Mechanistically, Raf-1 is recruited to VE-cadherin complexes by a mechanism involving the small G protein Rap1 and is required to bring the Rho effector Rok-α to nascent AJs. This Raf-1-mediated fine tuning of Rok-α signaling allows the activation of junctional myosin and the timely maturation of AJ essential for maintaining cell cohesion during sprouting angiogenesis