Structure and Functions of Human Serum Albumin in Normal Conditions and in Patients with Liver Cirrhosis

The aim: to highlight the main points of albumin synthesis, posttranslational modifications and functions in normal conditions and in patients with liver cirrhosis.Key points. Albumin is the most abundant protein in blood plasma. Along with oncotic properties, albumin performs transport, antioxidant, immunomodulatory and endothelioprotective functions. Serum albumin in patient with liver cirrhosis undergoes modifications, leading to functional impairment. Human serum albumin is a compaund of human mercaptalbumin with cysteine residues having a reducing ability, and oxidized human non-mercaptalbumin. The proportion of irreversibly oxidized non-mercaptalbumin-2 with impaired functional activity increases in liver cirrhosis.Conclusion. The conformational structure of the albumin molecule plays an important role in maintaining its non-oncotic functions. Non-oncotic functions depend on albumin conformation. Further investigation of albumin conformation and albumin functions in patients with hepatic insufficiency can serve as an additional criterion for assessing the severity of cirrhosis and predictor of complications may become an additional criterion to new clinical applications and treatment strategies of liver failure

The Role of Correcting Structural and Functional Albumin Properties in Ascites Control in Decompensated Cirrhotic Patients

Аim: to study the structural and functional characteristics of albumin in patients with decompensated cirrhosis, their relationship with ascites; to identify the relationship between improvement in albumin characteristics and regression of ascites.Materials and methods. Fifty patients with decompensated liver cirrhosis and ascites were divided into groups. The first group received standard treatment for cirrhosis, the second — standard treatment and replacement therapy with 20 % human albumin solution at a dose of 200 mL per week for 3 months.Results. The value of the native conformation of albumin and the functional parameters of albumin were significantly lower than in the group of healthy individuals (p < 0.001). With the severity of ascites, the native conformation index (DR), which characterizes the structural usefulness of the albumin molecule, decreased. Median DR for ascites stage I (IAC) was –1.69, II grade — –2.28, III grade — –2.42 (p < 0.05). Replacement therapy with albumin allowed to achieve regression of ascites in 48.4 % of patients, compared with 7.1 % in the standard treatment group. Along with clinical improvement, restoration of albumin structural and functional properties was observed in the albumin group. The mean serum albumin level at which ascites remained in remission for 3 months was 42.11 g/L (p < 0.001).Conclusions and discussion. The structural and functional characteristics of albumin were impaired in patients with decompensated cirrhosis and ascites. The severity of changes in the structural and functional properties of albumin depended on the severity of ascites. The regression of ascites was accompanied by the restoration of the functional and structural usefulness of albumin against the backdrop of albumin replacement therapy. The criterion for stopping transfusion therapy with albumin can be the achievement of a serum albumin level of 42.11 ± 7.04 g/L, DR — 1.05, BE — 73.51 %, RTQ — 75.10 %, DTE — 72.71 %

Changes in the Structural and Functional Albumin Properties in Patients with Decompensated Liver Cirrhosis

Аim: to conduct a comparative analysis of serum albumin's structural and functional properties in decompensated cirrhotic patients by means of spin prob EPR spectroscopy.Materials and methods. The main study group included 70 patients with decompensated liver cirrhosis and ascites. The control group consisted of 12 healthy volunteers, comparable in gender and age, without liver diseases. To assess the structural and functional ability, serum albumin was analyzed by EPR spectroscopy.Results. Albumin levels within reference intervals were found in 37 patients (59.8 %). The native albumin index decrease in cirrhotic patients as the disease progressed with the lowest values in the Child – Pugh C group (p < 0.001). The binding efficiency of albumin decreased in accordance with the severity of cirrhosis with minimal albumin binding capacity in the Child – Pugh C (Me = 25.43 %; n = 30; p < 0.001). The transport activity of RTQ albumin decreased in patients with decompensated cirrhosis, the lowest transport ability was observed in the Child – Pugh C group (Me = 26.09 %). In patients with decompensated disease the detoxification potential was significantly reduced: Child – Pugh B — Me = 44.03 %; Child – Pugh C — Me =17.16 %. Despite the normal values of serum albumin in 72.5% of patients with cirrhosis B and in 26.7% in the cirrhosis C group, only 12.3% in the cirrhosis B group had normal albumin function and in cirrhosis C nо patients had normal albumin function.Conclusion. There were not only serum concentration depletion in cirrhotic patients, but also albumin physiological non-oncotic properties were violated. The severity of these changes increased with the progression of cirrhosis. Our data allow us to raise the question of the need to use the EPR test to determine indications for albumin replacement therapy in patients with cirrhosis and the presence of ascites, even at normal values of its serum concentration

Soluble CD44 Interacts with Intermediate Filament Protein Vimentin on Endothelial Cell Surface

CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12–37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells

Catching-up in the global factory: analysis and policy implications

MNEs shape the location of activities in the world economy, linking diverse regions in what has been called the global factory. This study portrays the evolution of incomes and employment in the global factory using a quantitative input–output approach. We find emerging economies forging ahead relative to advanced economies in income derived from fabrication activities, handling the physical transformation process of goods. In contrast, convergence in income derived from knowledge-intensive activities carried out in pre- and post-fabrication stages is much slower. We discuss possible barriers to catching-up and policy implications for emerging economies in developing innovation capabilities, stressing the pivotal role of MNEs

FDI and regional development policy

The transformations in the worldwide division of labour brought about by globalisation and technological change have shown an unintended negative effect, particularly evident in advanced economic systems: uneven spatial distribution of wealth and rising within-country inequality. Although the latter has featured prominently in recent academic and policy debates, in this paper we argue that the relevance of connectivity (here proxied by foreign capital investments, FDI) for regional economic development is still underestimated and suffers from a nation-biased perspective. As a consequence, the relationship between the spatial inequality spurred by the global division of labour and the changes in the structural advantages of regions remains to be fully understood in its implications for economic growth, territorial resilience and industrial policy. Furthermore, even though connectivity entails bi-directional links – i.e. with regions being simultaneously receivers and senders – attractiveness to foreign capital has long been at the centre of policy attention whilst internationalisation through investment abroad has been disregarded, and sometimes purposely ignored, in regional development policy agendas. We use three broad-brushed European case-studies to discuss some guiding principles for a place-sensitive regional policy eager to integrate the connectivity dimension in pursuing local economic development and territorial equity

Changing perspectives on the internationalization of R&D and innovation by multinational enterprises: a review of the literature

Internationalization of R&D and innovation by Multinational Enterprises (MNEs) has undergone a gradual and comprehensive change in perspective over the past 50 years. From sporadic works in the late 1950s and in the 1960s, it became a systematically analysed topic in the 1970s, starting with pioneering reports and “foundation texts”. Our review unfolds the theoretical and empirical evolution of the literature from dyadic interpretations of centralization versus decentralization of R&D by MNEs to more comprehensive frameworks, wherein established MNEs from Advanced Economies still play a pivotal role, but new players and places also emerge in the global generation and diffusion of knowledge. Hence views of R&D internationalization increasingly rely on concepts, ideas and methods from IB and other related disciplines such as industrial organization, international economics and economic geography. Two main findings are highlighted. First, scholarly research pays an increasing attention to the network-like characteristics of international R&D activities. Second, different streams of literature have emphasized the role of location- specific factors in R&D internationalization. The increasing emphasis on these aspects has created new research opportunities in some key areas, including inter alia: cross-border knowledge sourcing strategies, changes in the geography of R&D and innovation, and the international fragmentation of production and R&D activities

Comparative assessment of various composite materials and natural natural tooth tissue translucencies

Objectives: The aim of this study was to compare the translucency levels of various composite materials that are positioned by their manufacturers as 'dentin,' 'opaque,' 'body,' and 'enamel' in relation to natural tooth tissues. Methods: Sixteen commercial composite materials and 10 natural tooth tissue samples (enamel and dentin) were studied. The differences in color of dried and hydrated samples were measured on a black-and-white background using CIELab coordinates. Analysis of variance (ANOVA) and Kruskal-Wallis tests were used to compare the translucency parameter (TP) values of the different materials (P < 0.05), and t test was used to compare the TP values for the dried and hydrated samples, with the significance set at P < 0.001. Results: The TP values of opaque shades for the.studied composite materials ranged from 1.5 to 3.9, and those of enamel shades from 3.9 to 10.9. According to the obtained results, a body shade sample had a high level of translucency, comparable with some enamel shades of the materials studied (TP = 4.489 +/- 0.505 after polymerization, and 3.916 +/- 0.566 after 48 h of water storage). The translucency levels of dry composite samples and samples after hydration were not significantly different, while significant changes were observed for dentin and enamel (P < 0.05). Significance: Choosing a composite material that is suitable for different clinical situations is a major challenge in everyday dental practice. Information about the relative translucency of various composites on the market and their compliance with natural tissues can help dentists to choose optimal restorative materials. [GRAPHICS]