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
- Butadienes * MeSH
- Mass Spectrometry MeSH
- Vitamin K 2 chemistry MeSH
- Publication type
- Journal Article 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
- Anticoagulants therapeutic use MeSH
- Administration, Oral MeSH
- Stroke * prevention & control etiology MeSH
- Atrial Fibrillation * drug therapy complications MeSH
- Risk Assessment methods MeSH
- Factor Xa Inhibitors * therapeutic use administration & dosage MeSH
- Humans MeSH
- Pyrazoles * therapeutic use MeSH
- Pyridones * therapeutic use adverse effects administration & dosage MeSH
- Randomized Controlled Trials as Topic methods MeSH
- Registries MeSH
- Rivaroxaban * administration & dosage therapeutic use MeSH
- Risk Factors MeSH
- Aged MeSH
- Vitamin K antagonists & inhibitors MeSH
- Patient Selection * MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study 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
- Cystic Fibrosis * blood MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Vitamin K Deficiency blood MeSH
- Nutritional Status MeSH
- Dietary Supplements MeSH
- Prothrombin * analysis MeSH
- Cross-Sectional Studies MeSH
- Vitamin K 1 * administration & dosage blood MeSH
- Vitamin K 2 * blood analogs & derivatives MeSH
- Vitamin K blood MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article 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
- Anticoagulants adverse effects MeSH
- Stroke * prevention & control complications MeSH
- Adult MeSH
- Atrial Fibrillation * complications diagnosis surgery MeSH
- Consensus MeSH
- Hemorrhage chemically induced prevention & control MeSH
- Physicians * MeSH
- Humans MeSH
- Atrial Appendage * surgery MeSH
- Thromboembolism * etiology prevention & control MeSH
- Left Atrial Appendage Closure MeSH
- Vitamin K MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Gastrointestinal Hemorrhage chemically induced therapy MeSH
- Hemophilia A complications MeSH
- Hemorrhage * therapy MeSH
- Humans MeSH
- Adolescent MeSH
- Protein C Deficiency complications MeSH
- Infant, Newborn MeSH
- Aged MeSH
- Vitamin K pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Infant, Newborn MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Newspaper Article MeSH
- MeSH
- Anticoagulants pharmacology therapeutic use MeSH
- Atrial Fibrillation etiology complications MeSH
- Platelet Aggregation Inhibitors pharmacology therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Heart Disease Risk Factors MeSH
- Heart Failure * drug therapy complications MeSH
- Thromboembolism * etiology physiopathology therapy MeSH
- Vitamin K antagonists & inhibitors MeSH
- Patient Education as Topic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review 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.
- Keywords
- hypervitaminóza,
- MeSH
- Avitaminosis etiology drug therapy physiopathology MeSH
- Humans MeSH
- Vitamin A Deficiency etiology drug therapy physiopathology MeSH
- Vitamin D Deficiency etiology drug therapy physiopathology MeSH
- Vitamin E Deficiency etiology drug therapy physiopathology MeSH
- Vitamin K Deficiency etiology drug therapy physiopathology MeSH
- Vitamin A physiology therapeutic use MeSH
- Vitamin D physiology therapeutic use MeSH
- Vitamin E physiology therapeutic use MeSH
- Vitamin K physiology therapeutic use MeSH
- Recommended Dietary Allowances MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review 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
- Clinical Laboratory Techniques methods MeSH
- Humans MeSH
- NAD metabolism MeSH
- Biomarkers, Tumor analysis MeSH
- Breast Neoplasms * diagnosis pathology MeSH
- Poly (ADP-Ribose) Polymerase-1 analysis metabolism MeSH
- Sirtuin 1 analysis metabolism MeSH
- Superoxide Dismutase analysis metabolism MeSH
- Vitamin K analysis MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
- MeSH
- Anticoagulants * adverse effects therapeutic use MeSH
- Atrial Fibrillation drug therapy MeSH
- Risk Assessment MeSH
- Clinical Studies as Topic MeSH
- Frail Elderly MeSH
- Humans MeSH
- Music Therapy * MeSH
- Infant, Newborn MeSH
- Pain, Postoperative MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Vitamin K antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Aged, 80 and over MeSH
- Aged MeSH
Matrix Gla protein (MGP) je cirkulující protein s nízkou molekulární hmotností, který působí jako přirozený inhibitor kalcifikace. Řadíme ho do skupiny proteinů označených jako vitamin K dependentní proteiny. Jeho hlavní funkcí je prevence ukládání vápníku do měkkých tkání. Pro správné fungování musí být MGP dostatečně karboxylován a fosforylován, což je proces, který vyžaduje vitamin K2 jako kofaktor gamma-glutamylkarboxylasy. Nedostatek vitaminu K se projevuje kardiovaskulárním onemocněním, nedostatečnou mineralizací kostní tkáně a vznikem kalcifikujících deposit v měkkých tkáních. Cílem práce bylo navržení metod pro sledování hladiny MGP a defosforylovaného nedostatečně karboxylovaného MGP (dp-uc MGP) za využití imunochemické detekce a aplikovat je na analýzu reálných pacientských vzorků pro použití v klinických laboratořích, kde by tyto markery mohly sloužit jako potencionální markery závažnosti kloubních onemocnění, kardiovaskulárních onemocnění a také jako markery vypovídající o stavu vitaminu K v organismu.
Matrix Gla protein (MGP) is a circulating protein with a low molecular weight that acts as a natural inhibitor of calcification. It belongs to the group of vitamin K‐dependent proteins. For its proper function, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Its main function is the prevention of soft-tissue calcification. It requires vitamin K2 as a cofactor for gamma glutamyl carboxylase. Vitamin K insufficiency is manifested by cardiovascular diseases, insufficient mineralization of bone tissue and the formation of calcifying deposits in soft tissues. The aim of this study was to design methods for monitoring the levels of MGP and dp-uc MGP by using immunochemical detection and to apply them to the analysis of real samples for use in clinical laboratories. These markers could serve as potential markers of the severity of joint diseases, cardiovascular diseases and also as markers indicating the status of vitamin K in organism.
