Thermophilic bacteria of four genera in contrast to the commonly used production strains such as Bacillus subtilis, produce homologs other than menaquinone (MK) with seven isoprene units. The number of isoprene units and the configuration of double bonds are essential factors for their biological activity. The goal was to obtain a strain of bacteria that produces a wide range of MK homologs and only all-trans geometrical isomers, which was the strain G. kaustophilus. Using off-line two-dimensional LC-tandem MS in columns with the RP18 phase and the COSMOSIL cholester phase (separation according to the geometric configuration of double bonds) it was shown that thermophilic bacteria grown at different temperatures produce only all-trans isomers of menaquinones from MK-5 (menaquinone with five isoprenyl units) to MK-15 (fifteen isoprenyl units). Therefore, G. kaustophilus appears to be a biotechnologically important strain produces only trans isomers and additionally homologs from 5 to 15 isoprene units.

• MeSH
• Bacteria * MeSH
• butadieny * MeSH
• hmotnostní spektrometrie MeSH
• vitamin K 2 chemie   MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry. METHODS: Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA. RESULTS: Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs. CONCLUSION: Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• aplikace orální MeSH
• cévní mozková příhoda * prevence a kontrola   etiologie   MeSH
• fibrilace síní * farmakoterapie   komplikace   MeSH
• hodnocení rizik metody   MeSH
• inhibitory faktoru Xa * terapeutické užití   aplikace a dávkování   MeSH
• lidé MeSH
• pyrazoly * terapeutické užití   MeSH
• pyridony * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• registrace MeSH
• rivaroxaban * aplikace a dávkování   terapeutické užití   MeSH
• rizikové faktory MeSH
• senioři MeSH
• vitamin K antagonisté a inhibitory   MeSH
• výběr pacientů * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, p < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, p = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.

• MeSH
• cystická fibróza * krev   MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nedostatek vitaminu K krev   MeSH
• nutriční stav MeSH
• potravní doplňky MeSH
• protrombin * analýza   MeSH
• průřezové studie MeSH
• vitamin K 1 * aplikace a dávkování   krev   MeSH
• vitamin K 2 * krev   analogy a deriváty   MeSH
• vitamin K krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

• MeSH
• antikoagulancia škodlivé účinky   MeSH
• cévní mozková příhoda * prevence a kontrola   komplikace   MeSH
• dospělí MeSH
• fibrilace síní * komplikace   diagnóza   chirurgie   MeSH
• konsensus MeSH
• krvácení chemicky indukované   prevence a kontrola   MeSH
• lékaři * MeSH
• lidé MeSH
• síňové ouško * chirurgie   MeSH
• tromboembolie * etiologie   prevence a kontrola   MeSH
• uzávěr ouška levé síně MeSH
• vitamin K MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• gastrointestinální krvácení chemicky indukované   terapie   MeSH
• hemofilie A komplikace   MeSH
• krvácení * terapie   MeSH
• lidé MeSH
• mladiství MeSH
• nedostatek proteinu C komplikace   MeSH
• novorozenec MeSH
• senioři MeSH
• vitamin K farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• novinové články MeSH

• MeSH
• antikoagulancia farmakologie   terapeutické užití   MeSH
• fibrilace síní etiologie   komplikace   MeSH
• inhibitory agregace trombocytů farmakologie   terapeutické užití   MeSH
• klinická studie jako téma MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• srdeční selhání * farmakoterapie   komplikace   MeSH
• tromboembolie * etiologie   patofyziologie   terapie   MeSH
• vitamin K antagonisté a inhibitory   MeSH
• vzdělávání pacientů jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

This article summarizes current information about the function, source, and bioavailability of fat-soluble vitamins A, D, E, and K. Furthermore, it shows dietary reference values stated by European Food Safety Authority for the adult population, lists hypovitaminosis high-risk groups and states potential complications that could arise from ingesting these compounds.

Článek podává shrnutí aktuálních informací o funkci, zdrojích a biologické dostupnosti liposolubilních vitaminů A, D, E a K. Dále uvádí výživové referenční hodnoty dle Evropského úřadu pro bezpečnost potravin pro dospělou populaci, důsledky, rizikové skupiny pro vznik hypovitaminóz a možné komplikace při vysokém příjmu těchto sloučenin.

• Klíčová slova
• hypervitaminóza,
• MeSH
• avitaminóza etiologie   farmakoterapie   patofyziologie   MeSH
• lidé MeSH
• nedostatek vitaminu A etiologie   farmakoterapie   patofyziologie   MeSH
• nedostatek vitaminu D etiologie   farmakoterapie   patofyziologie   MeSH
• nedostatek vitaminu E etiologie   farmakoterapie   patofyziologie   MeSH
• nedostatek vitaminu K etiologie   farmakoterapie   patofyziologie   MeSH
• vitamin A fyziologie   terapeutické užití   MeSH
• vitamin D fyziologie   terapeutické užití   MeSH
• vitamin E fyziologie   terapeutické užití   MeSH
• vitamin K fyziologie   terapeutické užití   MeSH
• výživové doporučené dávky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Cancer cells have a special energy metabolism that enables them to multiply quickly. Under normal oxygen conditions, the Warburg effect is a distinguishing aspect of cancer metabolism in which anaerobic glycolysis is favored. Enhanced glycolysis also helps to produce nucleotides, amino acids, lipids, and folic acid, all of which are necessary for cancer cell division. In a variety of metabolic processes, including glycolysis, the co-enzyme nicotinamide adenine dinucleotide (NAD) mediates redox reactions. NAD levels that are higher promote glycolysis and supply energy to cancer cells. NAD metabolism, like energy metabolism, is linked in cancer genesis and could be a potential therapeutic target for cancer treatment. In this research, NAD-consuming enzymes, poly(ADP-ribose) polymerase (PARP) and SIRT1, have been investigated in breast cancer patients, in addition to detect the levels of serum malondialdehyde (MDA), superoxide dismutase (SOD) and vitamin K levels. Sixty participants were enrolled in this study, 30 women with breast cancer and 30 controls. Serum were analysed for determination of the levels of PARP1, SIRT1, MDA, SOD, and vitamin K. The results showed a drop in the expression levels of PARP and that was concomitant with the elevation in the expression levels of SIRT1 and MDA, in addition to the drop in SOD and vitamin K levels. These findings suggest that SIRT1 might be the most NAD-consuming enzyme in cancerous cells rather than PARP (the DNA repair enzyme), and this increase in MDA with the drop in SOD and vitamin K might be associated with the increase in cell proliferation and a decrease in apoptotic cell death. Finally, this study could be used as a treatment option for patients with breast cancer. could be used as a treatment option for patients with breast cancer.

• MeSH
• klinické laboratorní techniky metody   MeSH
• lidé MeSH
• NAD metabolismus   MeSH
• nádorové biomarkery analýza   MeSH
• nádory prsu * diagnóza   patologie   MeSH
• poly(ADP-ribosa)polymerasa 1 analýza   metabolismus   MeSH
• sirtuin 1 analýza   metabolismus   MeSH
• superoxiddismutasa analýza   metabolismus   MeSH
• vitamin K analýza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

1, 4-naphthoquinone, a plant-based quinone derivative, has gained much attention for its effectiveness against several biofilm-linked diseases. The biofilm inhibitory effect of 1, 4-naphthoquinone against Staphylococcus aureus has already been reported in our previous study. We observed that the extracellular DNA (eDNA) could play an important role in holding the structural integrity of the biofilm. Hence, in this study, efforts have been directed to examine the possible interactions between 1, 4-naphthoquinone and DNA. An in silico analysis indicated that 1, 4-naphthoquinone could interact with DNA through intercalation. To validate the same, UV-Vis spectrophotometric analysis was performed in which a hypochromic shift was observed when the said molecule was titrated with calf-thymus DNA (CT-DNA). Thermal denaturation studies revealed a change of 8°C in the melting temperature (Tm) of CT-DNA when complexed with 1, 4-naphthoquinone. The isothermal calorimetric titration (ITC) assay revealed a spontaneous intercalation between CT-DNA and 1, 4-naphthoquinone with a binding constant of 0.95 ± 0.12 × 108. Furthermore, DNA was run through an agarose gel electrophoresis with a fixed concentration of ethidium bromide and increasing concentrations of 1, 4-naphthoquinone. The result showed that the intensity of ethidium bromide-stained DNA got reduced concomitantly with the gradual increase of 1, 4-naphthoquinone suggesting its intercalating nature. To gain further confidence, the pre-existing biofilm was challenged with ethidium bromide wherein we observed that it could also show biofilm disintegration. Therefore, the results suggested that 1, 4-naphthoquinone could exhibit disintegration of the pre-existing biofilm of Staphylococcus aureus through eDNA intercalation.

• MeSH
• biofilmy MeSH
• DNA farmakologie   MeSH
• ethidium farmakologie   MeSH
• lidé MeSH
• naftochinony * farmakologie   MeSH
• stafylokokové infekce * MeSH
• Staphylococcus aureus genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A series of 11-substituted 9-hydroxy-3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones 3.1-3.13 were synthesized via hetero-Diels-Alder reaction of 5-ene-4-thioxo-2-thiazolidinones and 5-hydroxy-1,4-naphthoquinone (juglone). The structure of newly synthesized compounds was established by means of spectral data and a single-crystal X-ray diffraction analysis. The synthesized compounds were tested on a panel of cell lines representing different types of cancer as well as normal and pseudonormal cells and peripheral human blood lymphocytes. Compound 3.10 was found to be the most active derivative, exhibiting a cytotoxic effect similar to doxorubicin's one (IC50 ranged from 0.6 to 5.98 μM), but less toxic to normal and pseudonormal cells. All synthesized compounds were able to interact with DNA, although their anticancer activity did not correlate with the potency of interaction with DNA. The status of p53 in colorectal cancer cells correlated with the activity of the synthesized derivatives 3.1, 3.7, and 3.10. Compound 3.10 did not have an acute toxic effect on the body of С57BL/6 mice, unlike the well-known anticancer drug doxorubicin, which was used as a positive control. The injection of 3.10 (20 mg/kg) to mice had no effect on the counts of leukocytes, erythrocytes, platelets and hemoglobin level in their blood, in contrast to doxorubicin, which caused anemia and leukopenia, indicating bio-tolerance of 3.10in vivo.

• MeSH
• doxorubicin farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• naftochinony * farmakologie   MeSH
• proliferace buněk MeSH
• protinádorové látky * chemie   MeSH
• screeningové testy protinádorových léčiv MeSH
• simulace molekulového dockingu MeSH
• thiazoly chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH