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During the last decades several new drug formulations were developed to target the central nervous system (CNS) from the nasal cavity. However, in these studies less attention was paid to the possible drug-drug interactions in case of multi-drug therapy. In our pilot study first we compared a nasal solution and a nasal gel to demonstrate their distribution in the nasal cavity (3D printed rat skull model and histology). Due to the aspiration induced high mortality at administration of nasal solution the study was continued only with the gel formulation of quinidine. The aim of our experiments was to identify the possible functional role of P-glycoprotein (P-gp) in the drug absorption in nasal cavity and to test drug-drug interactions at nose-to-brain delivery. Therefore, a P-gp substrate model drug, quinidine was tested by intranasal (IN) administration in presence of PSC-833 (specific P-gp inhibitor) given intravenously (IV) or IN and adrenaline (IN) at low (50 ng) or high (20 μg) dose. In control animals the brain penetration of quinidine was at the level of detection limit, but in combination therapy with IV PSC-833 the brain levels increased dramatically, similarly to high dose IN adrenalin, where due to vasoconstriction peripheral distribution was blocked. These results indicate that P-gp has an important role in drug absorption and efflux at nasal cavity, while adrenaline is also able to modify the penetration profile of the P-gp substrate model drug at nasal application as it decreases nose-to-blood absorption, letting more quinidine to reach the brain along with the nasal nerves.

Differences in regional economic growth trajectories and the multiple regional effects of the economic crisis have revived studies dedicated to the subject of resilience. The main goal of this paper is to measure the resilience of the Romanian regions, seeking to answer two basic questions: What was the regional impact of the global crisis from 2008 onwards? How have the Romanian regions recovered following the crisis? We focus our analysis on the region with the highest economic growth in the post-crisis period (South-East) in order to understand the main drivers of economic recovery. The methodology of the study involves a multi-dimensional understanding of resilience. This means that we have extended our focus from economic indicators towards a more inclusive methodology related to the measurement of regional well-being. Our main finding is that productivity growth was a critical driver of economic recovery, having a significant impact on income and jobs, as well as influencing non-material elements of well-being.

Our paper focuses on the spatial differentiation of economic development in Romania. We use spatial econometric methods (spatial autocorrelation) in order to determine the differentiation of the country in core regions and peripheries. The analysis is carried out on the regional spatial scale (NUTS 3 units or counties) and covers the period 2000-2011. The main results show a pronounced spatial polarization and spatial autocorrelation of economic development (proxied by GDP per capita) in Romania in some core regions (the capital Bucharest), while an extended periphery, comprising the eastern part of Transylvania, Moldova and northern Muntenia is lagging behind. The analysis of the multidimensional development (Human Development Index) has revealed the existence of some regional polarizing centres (Iași, Constanța), while the spatial configuration of cores and peripheries shows a different picture: beside the capital region, there is a second core area in the central part of Transylvania, while the eastern periphery is centred on the county Brăila.

The paper discusses the post-communist development and evolution of the regionalization process in Romania. In the frst part, we distin-guish between two periods of regionalization: the preparation period for the EU accession, and the post-accession period. It turns out that the process of regionalization was oriented to EU criteria and expectations, which are in turn low in what it concerns the establishment of regional development institutions and of different territori-al levels of the NUTS system. A radical change into this question was introduced very recently, at the beginning of 2013, when different region-alization projects have been launched by politi-cal parties and academics as well. Therefore, in the second part of the paper our main aim is to analyze the latest regionalization projects and scenarios, emphasizing one of the most contro-versial questions of this process related to the ethno-cultural diversity of the country and to the question of Székelyland.