Inhibition of NF-κB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol)

French maritime pine bark extract (Pycnogenol(®)) displays a variety of anti-inflammatory effects in vivo. Aim of this study was to determine whether human plasma after oral intake of Pycnogenol contains sufficient concentrations of active principles to inhibit key mediators of inflammation. Blood samples from seven healthy volunteers were obtained before and after five days administration of 200 mg Pycnogenol per day. Plasma samples statistically significantly inhibited matrix metalloproteinase 9 (MMP-9) release from human monocytes and NF-κB activation. Thus, we provide evidence that bioavailable active principles of Pycnogenol exert anti-inflammatory effects by inhibition of proinflammatory gene expression which is consistent with documented clinical observations. We suggest that our ex vivo method is suitable to substantiate molecular pharmacological mechanisms of complex plant extracts in a more focussed and rational way compared to in vitro studies by taking into account the processes of absorption and metabolism

The impact of probiotics and vitamin C on the prevention of upper respiratory tract symptoms in two preschool children cohorts

BACKGROUND/OBJECTIVES The efficacy of Lab4 probiotic and vitamin C combination on the prevention of upper respiratory tract infections (URTIs) was investigated in two studies with children. Our objective was to pool dataset of 57 preschool children from the PROCHILD study (ISRCTN28722693) and the dataset of 50 preschool matched cohort from the PROCHILD-2 study (ISRCTN26587549) to evaluate the impact of probiotic/vitamin C combination on the prevention of upper respiratory tract symptoms and provide a more robust assessment of effect using detailed individual level data. SUBJECTS/METHODS The children were supplemented daily for 6 months with either the multistrain probiotic (1.25×1010 cfu/tablet consisting of two strains of Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) plus 50 mg vitamin C or a placebo. RESULTS In the pooled analysis of the individual participant data (per protocol population), significant reductions were observed for the incidence (−25%; 95% confidence interval [CI], 0.66, 0.85; P < 0.0001) and duration (−14.9 days; 95% CI, −24.8, −5.1; P = 0.0030) of typical URTI symptoms in the active group compared with the placebo. The incidence rates of absenteeism from preschool (IR ratio, 0.75; 95% CI, 0.66, 0.86; P < 0.0001), paediatric visits (IR ratio, 0.56; 95% CI, 0.47; 0.68; P < 0.0001) and antibiotic usage (IR ratio, 0.53; 95% CI, 0.39, 0.71; P < 0.0001) were also significantly reduced. CONCLUSION The pooled analysis findings of comparable preschool cohorts from two studies indicate that the supplementation with probiotic and vitamin C combination is beneficial in the prevention and management of URTI symptoms

The kynurenine and serotonin pathway, neopterin and biopterin in depressed children and adolescents: an impact of omega-3 fatty acids, and association with markers related to depressive disorder. A randomized, blinded, prospective study

Depressive disorder is a severe mental condition. In addition to genetic factors, immunological-inflammatory factors, oxidative stress, and disturbances in neurotransmitter metabolism, kynurenine and serotonin pathways may play a role. The exact mechanisms, especially in depressed children and adolescents, are not fully understood. Our primary hypothesis was whether the metabolites of tryptophan degradation in children and adolescents with depressive disorder might be influenced by omega-3 FAs compared to omega-6 FAs during a 12-week supplementation. A secondary hypothesis was to investigate whether tryptophan metabolites in children and adolescents are associated with markers of inflammatory response, oxidative stress, cortisol, and the serum omega-6/omega-3 FA ratio. Metabolites of tryptophan degradation and pteridines, neopterin, and biopterin in urine were analyzed with an HPLC system. Surprisingly, omega-3 FAs stimulated both kynurenine (kynurenine/tryptophan ratio) and serotonin (5-hydroxytryptophan) pathways, whereas omega-6 FAs only increased the kynurenine/tryptophan ratio. Neopterin and biopterin were not different from the healthy controls. Biopterin increased after omega-3 FA supplementation. Serotonin was positively correlated with lipoperoxidation and a marker of oxidative protein damage. Of the monitored tryptophan metabolites, only 5-hydroxyindolacetic acid was positively correlated with the severity of depression, total cholesterol, and negatively with brain-derived neurotrophic factor and glutathione peroxidase. In conclusion, in children and adolescents, both supplemented FAs stimulated the kynurenine pathway (kynurenine/tryptophan ratio) and kynurenine formation. However, the serotonin pathway (5-hydroxytryptophan) was stimulated only by omega-3 FA. Tryptophan metabolism is associated with oxidative stress, inflammation, total cholesterol, and cortisol. We are the first to point out the association between the kynurenine pathway (KYN/TRP ratio) and the omega-6/omega-3 FA ratio. The metabolite 5-HIAA could play a role in the pathophysiology of depressive disorder in children and adolescents.Clinical Trial Registrationhttps://www.isrctn.com/ISRCTN81655012, identifier ISRCTN81655012

Heme oxygenase-1 may affect cell signalling via modulation of ganglioside composition

Heme oxygenase 1 (Hmox1), a ubiquitous enzyme degrading heme to carbon monoxide, iron, and biliverdin, is one of the cytoprotective enzymes induced in response to a variety of stimuli, including cellular oxidative stress. Gangliosides, sialic acid-containing glycosphingolipids expressed in all cells, are involved in cell recognition, signalling, and membrane stabilization. Their expression is often altered under many pathological and physiological conditions including cell death, proliferation, and differentiation. The aim of this study was to assess the possible role of Hmox1 in ganglioside metabolism in relation to oxidative stress. The content of liver and brain gangliosides, their cellular distribution, and mRNA as well as protein expression of key glycosyltransferases were determined in Hmox1 knockout mice as well as their wild-type littermates. To elucidate the possible underlying mechanisms between Hmox1 and ganglioside metabolism, hepatoblastoma HepG2 and neuroblastoma SH-SY5Y cell lines were used for in vitro experiments. Mice lacking Hmox1 exhibited a significant increase in concentrations of liver and brain gangliosides and in mRNA expression of the key enzymes of ganglioside metabolism. A marked shift of GM1 ganglioside from the subsinusoidal part of the intracellular compartment into sinusoidal membranes of hepatocytes was shown in Hmox1 knockout mice. Induction of oxidative stress by chenodeoxycholic acid in vitro resulted in a significant increase in GM3, GM2, and GD1a gangliosides in SH-SY5Y cells and GM3 and GM2 in the HepG2 cell line. These changes were abolished with administration of bilirubin, a potent antioxidant agent. These observations were closely related to oxidative stress-mediated changes in sialyltransferase expression regulated at least partially through the protein kinase C pathway. We conclude that oxidative stress is an important factor modulating synthesis and distribution of gangliosides in vivo and in vitro which might affect ganglioside signalling in higher organisms

Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol) after oral administration to healthy volunteers

BACKGROUND: Since plant extracts are increasingly used as phytotherapeutics or dietary supplements information on bioavailability, bioefficacy and safety are warranted. We elucidated the plasma kinetics of genuine extract components and metabolites after single and multiple ingestion of the standardized maritime pine bark extract Pycnogenol (USP quality) by human volunteers. METHODS: Eleven volunteers received a single dose of 300 mg pine bark extract, five volunteers ingested 200 mg daily for five days to reach steady state concentrations. Plasma samples were obtained before and at defined time points after intake of the extract. Samples were analyzed by HPLC with ion-pair reagents and simultaneous UV and electrochemical detection. RESULTS: We quantified total plasma concentrations of catechin, caffeic acid, ferulic acid, taxifolin and the metabolite M1 (δ-(3,4-dihydroxy-phenyl)-γ-valerolactone). Additionally, we describe plasma time courses and steady state appearance of ten so far unknown compounds, U1 to U10. After single ingestion, compounds derived from the extract were rapidly absorbed and the majority of them were detectable over whole experimental period of 14 h. The analysis of steady state plasma samples revealed significant phase II metabolism. CONCLUSION: We present the first systematic pharmacokinetic analysis of compounds derived from maritime pine bark extract. Beyond the known constituents and metabolites we uncovered the plasma time courses of ten unknown compounds. In concert with our previous detection of anti-inflammatory bioefficacy of these plasma samples ex vivo we suggest that constituents and metabolites of Pycnogenol bear potential for disclosure of novel active principles

HR strategy in ČD Cargo, a.s.

Import 26/06/2013Personální strategie ve společnosti ČD Cargo, a.s. Úspěch podnikání závisí na lidech, kteří ve společnosti pracují. Lidský kapitál je největší bohatství společnosti. Společnost, která si chce zajistit přežití a růst musí do tohoto kapitálu investovat. Personální plánování patří mezi nejdůležitější část řízení lidských zdrojů. Diplomová práce se zabývá odhady potřeby zaměstnanců a pokrytí jejich potřeby ve společnosti. Cílem diplomové práce je zhodnotit současnou personální situaci ve společnosti ČD Cargo, a.s. a za využití tří vybraných metod vytvořit personální strategii společnosti. Diplomová práce s názvem „Personální strategie ve společnosti ČD Cargo,a.s.“ vznikla ve vzájemné spolupráci se zaměstnanci odboru Lidských zdrojů.HR strategy in ČD Cargo, a.s. Being successful in enterprise depends on people working for a particular company. Human capital is the fortune of companies. The company that wants to survive and grow has to make investment into it. Personnel planning makes one of the most important part of Human resources strategies. The thesis deals with the estimation of the number of employess needed by a company and meeting their needs. The aim of the thesis is to evaluate a contemporary situation in the Cargo company making a use of three methods of developing a company´s personnel strategy. The thesis named „HR strategy in ČD Cargo, a.s.“ has been produced with the mutual cooperation with the employees of the Human Resources department.152 - Katedra podnikohospodářskádobř

The current business environment of Austria

Hlavním tématem bakalářské práce je analýza současného podnikatelského prostředí Rakouska, které se po vstupu do Evropské unie stalo hlavním zájmem dalších členských států a srovnat toto podnikatelské prostředí s českým. Úvod je věnován definici pojmu podnikatelské prostředí z pohledu různých autorů. Následně je podnikatelské prostředí analyzováno pomocí PESTLE a SWOT analýzy. Závěr práce je věnován vývoji obchodních vztahů obou zemí, komparace jejich obchodních bilancí, komoditních struktur a následně rozbor bariér rozvoje vzájemných obchodních vztahů.Main topic of the bachelor thesis is the analysis of the current business environment in Austria, which, after joining the European Union, became the main interest of other member states. The business environment of Austria is compared with the business environment in the Czech Republic.The introduction is devoted to the definition of business environment from the point of views of various authors. Furthemore, the Austrian business environment is analysed using PESTLE and SWOT analysis and aligned with the Czech one. The conclusion of the thesis is dedicated to the development of trade relations between the two countries, comparison of Austria and the Czech Republic from the point of views of the trade balance, and commodity structure, and then to the analysis of barriers to the development of mutual trade relations

Remuneration of the employees in catering businesses

The topic of this diploma thesis is the remuneration of the employees in catering businesses in the Czech Republic with specific focus on the tipping component. The thesis itself is structured into 3 main chapters of which 2 of them are theoretical and the last one is practical. The theoretical parts investigate the explanation of the issue of remuneration as such for employees and its individual components and deals with the issue of tips as one of the main components of remuneration for employees in the catering businesses. Practical part of the thesis deals with research of importance of tips for employees in catering facilities. It contains description of methodology used in the research, results of the questionnaire survey as well as the interpretation of research results. Thesis reaches the conclusion that tips for employees in catering facilities represent very important part of their remuneration. Main findings of the theses are information on the real share of tips in the overall remuneration of employees as well as information on preferences of different tip payments methods by different social group of employees.Tématem diplomové práce je odměňování zaměstnanců stravovacích zařízení v České republice se specifickým zaměřením na složku spropitného. Samotná práce je strukturována do 3 hlavních kapitol, z čehož 2 kapitoly jsou teoretickou částí a 1 kapitola je částí práce. Teoretické části se zabývají vysvětlením problematiky odměňování jako takového u zaměstnanců a jeho jednotlivými složkami a poté se zabývá také problematikou spropitného jako jednou z hlavních složek odměňování u zaměstnanců stravovacích zařízení. Praktická část se potom věnuje výzkumu významu spropitného pro zaměstnance ve stravovacích zařízeních. Obsahuje použitou metodiku, výsledky dotazníkového šetření a interpretaci výsledků výzkumu. Práce dochází k závěru, že spropitné je velmi důležitou složkou mzdy zaměstnanců stravovacích zařízení. Hlavními zjištěními jsou informace o podílu spropitného na celkovém příjmu zaměstnance a o vztahu jednotlivých sociálních skupin zaměstnanců ke způsobu jeho výplaty