Innovation of costing system in metallurgical companies

Innovation means creating and implementing new ideas in theory and practice. Generally speaking, companies in the Czech Republic that don’t have a foreign owner behave very conservatively as far as the used costing system is concerned. This also applies to metallurgical companies and foundries. The decision on method of costing calculations should be included in the sphere of strategic decision-making. The strategy must also define how to use method so as to obtain new orders which, as a result, should lead to an increase in production volume, and thereby to higher capacity utilization and also to higher overall sales. The article discusses the innovation of costing system in metallurgical companies

Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = −0.94; P = 0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism

Background: The marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA?+?DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin.Methods: In a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA?+?DHA concentrate (5 g/day, containing ~2.8 g EPA?+?DHA; Omega-3), or (iv) pioglitazone and EPA?+?DHA concentrate (Pio&amp; Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA?+?DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers.Results: Omega-3 and Pio&amp; Omega-3 increased EPA?+?DHA content in serum phospholipids. Pio and Pio&amp; Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio&amp; Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio&amp; Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio&amp; Omega-3.Conclusion: Besides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA?+?DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy.Trial registration: EudraCT number 2009-011106-42.<br/

Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV) Based Delivery System

Francisella tularensisis a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA), chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensisSchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100) doses of F. tularensisLVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensisantigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensisproteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens

In-situ characterization of growth of isothermal ω phase in metastable β-Ti alloy TIMETAL LCB

Metastable β-Ti alloys exhibit various solid-solid phase transitions. Our study is focused on the characterization of the diffusion controlled β→ωiso phase transition. The particles of ω phase play an important part in thermomechanical treatment since they serve as heterogeneous nucleation sites for precipitation of finely dispersed particles of hexagonal α phase. The in-situ observation of the growth of particles of ω phase could be difficult by conventional techniques. However, it was shown recently that the ω phase significantly influences the elastic constants of the material, and the different forms of ω phase have different effects on the elastic anisotropy, as well as on the internal friction coefficients. Therefore, the β→ω phase transformation could be in-situ observed by the precise measurement of the tensor of elastic constants. In this contribution, we present the study of the kinetics of the β→ωiso phase transformation by resonant ultrasound spectroscopy. The polycrystalline samples of TIMETAL LCB alloy were in-situ examined by this technique during isothermal and non-isothermal ageing at temperatures up to 300 °C

Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: The effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids

Aims. The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle. Methods. L6 myotubes were cultured with PA, DHA or LA (0.4 mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured. Results. PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA. Conclusions. PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance