Возможности праксеологии в банковской сфере

Статья посвящена исследованию сущности и возможностей использования основных постулатов и концептов праксеологии в банковской сфере. Изучаются особенности взаимодействия праксеологии как философско-логической сферы, с одной стороны, и банковского бизнеса как практической сферы деятельности – с другой. Проанализированы возможности внедрения в банковский сектор таких понятий, как «элементарные действия», «инициатор», а также использования критериев праксеологических оценок. Определены условия применимости «техники борьбы» для успешного функционирования коммерческого банка на рынке финансовых услуг.Статтю присвячено дослідженню сутності та можливостей використання основних постулатів і концептів праксеології в банківській сфері. Вивчаються особливості взаємодії праксеології як філософськологічної сфери, з одного боку, і банківського бізнесу як практичної сфери діяльності – з другого. Проаналізовано можливості впровадження в банківський сектор таких понять,як «елементарні дії», «ініціатор», а також використання критеріїв праксеологічних оцінок. Визначено умови застосування «техніки боротьби» для успішного функціонування комерційного банку на ринку фінансових послуг.The article is investigates the nature and possibilities of using the basic tenets and concepts of praxeology in the banking sector. We study the peculiarities of interaction of praxeology as a philosophical-logical sphere, on the one hand, and the banking business – both the practical scope of the other.The possibilities of implementation in the banking sector such concepts as «basic action», «initiator» as well as the use of criteria prakseologicheskih ratings. Indicated by the conditions of applicability «fighting techniques» for the successful operation of a commercial bank in the financial services market

High yield production of human invariant chain CD74 constructs fused to solubility-enhancing peptides and characterization of their MIF-binding capacities

The HLA class II histocompatibility antigen gamma chain, also known as HLA-DR antigen-associated invariant chain or CD74, has been shown to be involved in many biological processes amongst which antigen loading and transport of MHC class II molecules from the endoplasmic reticulum to the Golgi complex. It is also part of a receptor complex for Macrophage Migration Inhibitory Factor (MIF), and participates in inflammatory signaling. The inhibition of MIF-CD74 complex formation is regarded as a potentially attractive therapeutic target in inflammation, cancer and immune diseases. In order to be able to produce large quantities of the extracellular moiety of human CD74, which has been reported to be unstable and protease-sensitive, different constructs were made as fusions with two solubility enhancers: the well-known maltose-binding domain and Fh8, a small protein secreted by the parasite Fasciola hepatica. The fusion proteins could be purified with high yields from Escherichia coli and were demonstrated to be active in binding to MIF. Moreover, our results strongly suggest that the MIF binding site is located in the sequence between the transmembrane and the membrane-distal trimerisation domain of CD74, and comprises at least amino acids 113-125 of CD74

E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cells

Activated endothelial cells play a pivotal role in the pathology of inflammatory disorders and thus present a target for therapeutic intervention by drugs that intervene in inflammatory signaling cascades, such as rapamycin (mammalian target of rapamycin (mTOR) inhibitor). In this study we developed anti-E-selectin immunoliposomes for targeted delivery to E-selectin over-expressing tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3.; hosphocholine (DPPC), Cholesterol, and 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleimide (DSPE-PEG- Mal) were loaded with rapamycin via lipid film hydration, after which they were further functionalized by coupling N-succinimidyl-S-acetylthioacetate (SATA)-modified mouse anti human E-selectin antibodies to the distal ends of the maleimidyl (Mal)-PEG groups. In cell binding assays, these immunoliposomes bound specifically to TNF-alpha activated endothelial cells. Upon internalization, rapamycin loaded immunoliposomes inhibited proliferation and migration of endothelial cells, as well as expression of inflammatory mediators. Our findings demonstrate that rapamycin-loaded immunoliposomes can specifically inhibit inflammatory responses in inflamed endothelial cells

PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium

Dactolisib (NVP-BEZ235, also referred to as: 'BEZ235' or 'BEZ') is a dual mTOR/PI3 K inhibitor that is of potential interest in the treatment of inflammatory disorders. This work focuses on formulation of BEZ-loaded polymeric nanoparticles composed of a blend of poly(D, L-lactide-co-glycolide) (PLGA) and poly(D, L-lactide-coglycolide)- poly(ethylene glycol)-2000 (PLGA-PEG). The nanoparticles were prepared by an oil/water emulsion solvent evaporation method, and were subsequently characterized for yield, encapsulation efficiency, morphology, particle size, drug-polymer interaction and in vitro drug release profiles. A targeted formulation was developed by conjugation of a S-acetyl-thioacetyl (SATA)-modified mouse-anti human E-selectin antibody to the distal end of PLGA-PEG-SPDP containing nanoparticles. Our results show the successful preparation of spherical PLGA/PLGA-PEG nanoparticles loaded with BEZ. The particle size distribution showed a range from 250 to 360 nm with a high (> 75%) BEZ encapsulation efficiency. Approximately 35% of the loaded BEZ was released within 10 days at 37 degrees C in a medium containing 5% bovine serum albumin (BSA). Evaluation of efficacy of anti E-selectin decorated BEZ-loaded nanoparticles was carried out in tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Confocal microscopy analysis showed that cellular uptake of the targeted nanoparticles and subsequent internalization. Cell functional assays, including migration assay and phosphowestern blot analysis of the mTOR and pI3K signaling pathways, revealed that the E-selectin targeted nanoparticles loaded with BEZ had a pronounced effect on inflammation-activated endothelial cells as compared to the non-targeted BEZloaded nanoparticles. In conclusion, E-selectin targeted nanoparticles have a high potential in delivering the potent mTOR/pI3K inhibitor dactolisib to inflamed endothelial cells and are an interesting nanomedicine for anti-inflammatory therapy

Rapid hepatic clearance of full length CCN-2/CTGF: a putative role for LRP1-mediated endocytosis

CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min). Immunosorbent assay and immunostaining showed that CCN-2 distributed mainly to the liver and was taken up by hepatocytes. Steady state clearance in rats, determined by continuous infusion of CCN-2, was fast (45 mL/kg/min). Renal CCN-2 clearance, determined by arterial and renal vein sampling, accounted for only 12 % of total clearance. Co-infusion of CCN-2 with receptor-associated protein (RAP), an antagonist of LDL-receptor family proteins, showed that RAP prolonged CCN-2 half-life and completely prevented CCN-2 internalization by hepatocytes. This suggests that hepatic uptake of CCN-2 is mediated by a RAP-sensitive mechanism most likely involving LRP1, a member of the LDL-receptor family involved in hepatic clearance of various plasma proteins. Surface plasmon resonance binding studies confirmed that CCN-2 is an LRP1 ligand. Co-infusion of CCN-2 with an excess of the heparan sulphate-binding protamine lowered the large initial distribution volume of CCN-2 by 88 % and reduced interstitial staining of CCN-2, suggesting binding of CCN-2 to heparan sulphate proteoglycans (HSPGs). Protamine did not affect clearance rate, indicating that RAP-sensitive clearance of CCN-2 is HSPG independent. In conclusion, unlike its amino-terminal fragment which is cleared by the kidney, fu

Paternal inflammatory arthritis is associated with a higher risk of miscarriage:results of a large multicentre study (iFAME-Fertility)

OBJECTIVES: Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA.METHODS: We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA.RESULTS: In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = &lt;0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015].CONCLUSIONS: This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.</p

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics

Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [ C max], area under the curve [AUC], distribution volume [ V d], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured C max ( n = 27) and AUC ( n = 33), and to a lesser extent V d and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy