- The Pharmacologic Management of Osteoporosis in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis. [Journal Article]
- JCJ Clin Densitom 2019 May 10
- CONCLUSIONS: There is a lack of high-quality evidence supporting the efficacy of any treatment of osteoporosis in PBC. This may be explained by lack of power in the included studies. However, our current understanding of PBC-related osteoporosis indicates that it results from decreased bone formation, which may explain the attenuated effect of traditional antiresorptive agents. Future studies should investigate newer anabolic bone agents.
- [Determination of vitamin K in animal foods]. [Journal Article]
- WSWei Sheng Yan Jiu 2019; 48(3):468-473
- CONCLUSIONS: The proposed method is successfully applied for the determination of vitamin K in animal foods. A variety of vitamin K are distributed differently in distinct animals.
- Quantitation of vitamin K1 in serum using online SPE-LC-MS/MS and the challenges of working with vitamin K. [Journal Article]
- JCJ Chromatogr B Analyt Technol Biomed Life Sci 2019 Jun 01; 1117:41-48
- Vitamin K1 (phylloquinone) is one of the vitamin Ks. Several studies have previously investigated the role of vitamin K1 status in respect to disease, but without consistent results. Since vitamin K …
Vitamin K1 (phylloquinone) is one of the vitamin Ks. Several studies have previously investigated the role of vitamin K1 status in respect to disease, but without consistent results. Since vitamin K deficiency has been associated with different disease states it is important to develop a biochemical analysis with sufficient sensitivity and a low limit of quantitation (LOQ). The vitamin Ks are very fat-soluble. This non-polar nature has given rise to several challenges during the method development, because vitamin K1 sticks to materials used during the process and is lost during evaporation. We found that reducing the sample preparation as much as possible offline, instead using online SPE-LC-MS/MS improves recovery and gives satisfactory chromatograms. An Protein BEH C4 column, 300 Å (50 × 2.1 mm, 1.7 μm particle size) was used as trap column and a Phenyl-Hexyl-LC-column, 100 Å (100 × 2.1 mm, 2.6 μm particle size) was used as analytical column. The mobile phases consisted of 30 μmol/L NH4F in water and 30 μmol/L NH4F in MeOH. A triple quadrupole tandem mass spectrometer with atmospheric pressure chemical ionization (APCI) ion source, positive ion mode, was used to perform the mass spectrometric measurements. The method is simple, highly sensitive and fast. The method was validated for vitamin K1 with good analytical performance. With a LOQ of 0.05 nmol/L it is to our knowledge the vitamin K1 method with lowest LOQ reported to date in the literature. It can easily be automated and applied in a routine diagnostic laboratory. Blood collection tubes with different additives were tested and showed no difference. Stability of vitamin K1 in serum was tested at different temperatures (-20 °C, 4 °C and in light and dark at 20 °C over a period of 30 days) and showed that vitamin K1 is light sensitive in serum even after only one day.
- Modelling electron transfer in photosystem I: limits and perspectives. [Journal Article]
- PPPhysiol Plant 2019; 166(1):73-87
- Uncovering the parameters underlying the electron transfer (ET) in photosynthetic reaction centres is of importance for understanding the molecular mechanisms underpinning their functionality. The re…
Uncovering the parameters underlying the electron transfer (ET) in photosynthetic reaction centres is of importance for understanding the molecular mechanisms underpinning their functionality. The reductive nature of most cofactors involved in photosynthetic ET makes the direct estimation of their properties difficult. Photosystem I (PSI) operates in a highly reducing regime, making the assessment of cofactor properties even more difficult. Kinetic modelling coupled to a non-adiabatic description of ET is a useful approach in overcoming this hindrance. Here we review the theory and modelling approaches that have been used in assessing parameters associated with ET reactions in PSI, with particular attention to ET reactions involving the phylloquinones and the iron-sulphur clusters. In most modelling studies, the goal is to estimate the driving force of ET, which is usually associated with the cofactor midpoint potentials. The driving force is sensitive to many factors, which define the ET rate, i.e. the reorganisation energy, the coupling with nuclear modes and the electronic matrix elements, which are explored and discussed here. The importance of an inclusive modelling of both forward and reverse ET processes is discussed and highlighted. It is shown that although estimates are indeed sensitive to the exact parameter sets employed in the modelling, a general consensus is still attained, pointing to a scenario where Δ G A 1 A → F X 0 / Δ G A 1 B → F X 0 is weakly endergonic/exergonic, respectively. It is emphasised that to further refine those estimates, it will require a joint effort between computational modelling and more wide-ranging experimental studies.
- Routine Use of Vitamin K in the Treatment of Cirrhosis-Related Coagulopathy: Is it A-O-K? Maybe Not, We Say. [Journal Article]
- P TP T 2019; 44(3):131-136
- Historically, coagulopathy related to cirrhosis has been managed primarily as a bleeding disorder. However, several recent studies have shown that patients with cirrhosis have an increased risk of bo…
Historically, coagulopathy related to cirrhosis has been managed primarily as a bleeding disorder. However, several recent studies have shown that patients with cirrhosis have an increased risk of both bleeding and clotting. These coagulopathic changes are a result of the decreased synthetic capabilities of the cirrhotic liver. Vitamin K is often given to correct prolonged prothrombin times (PT) in patients with cirrhosis. However, this practice is not well defined and its effectiveness is questionable. The objective of our literature review is to determine the effectiveness of vitamin K to correct coagulopathy in cirrhosis. This report evaluates data published between 1981 and 2017. Published articles relevant to vitamin K use in cirrhotic patients were reviewed and summarized. The available literature regarding the use of vitamin K in cirrhosis is limited, and the research published so far does not appear to support its use. The routine uses of vitamin K to correct PT/international normalized ratio in hepatic cirrhosis should be avoided unless further studies can demonstrate true clinical benefit.
- Effects of Obesity on Warfarin Reversal With Vitamin K. [Journal Article]
- CAClin Appl Thromb Hemost 2019 Jan-Dec; 25:1076029618824042
- Phytonadione (vitamin K1, VK) is fat soluble and may be sequestered by adipose tissue, thus potentially altering drug distribution in obese patients requiring warfarin reversal. This single-center re…
Phytonadione (vitamin K1, VK) is fat soluble and may be sequestered by adipose tissue, thus potentially altering drug distribution in obese patients requiring warfarin reversal. This single-center retrospective cohort study aimed to determine the effects of obesity (defined as body mass index [BMI] ≥ 30 kg/m2) on warfarin reversal following administration of VK in adult patients. The primary outcome was complete or partial warfarin reversal (defined as an international normalized ratio [INR] ≤ 2.0) within 72 hours post-VK administration. Of 688 identified patients, 215 were included in primary INR analysis. Mean BMIs for obese (n = 84) and nonobese (n = 131) patients were 37.3 and 24.3 kg/m2 (P < .001), and mean baseline INRs were 4.73 and 4.42 (P = .534), respectively. Within 72 hours post-VK administration, 70% and 69% of the obese and nonobese groups, respectively, achieved complete or partial warfarin reversal (P = .904). Multiple logistic regression determined baseline INR and concomitant fresh frozen plasma administration to be factors influencing warfarin reversal. These findings do not suggest obesity is significantly associated with a decreased likelihood of warfarin reversal within 72 hours post-VK administration.
- Direct-Acting Oral Anticoagulants and Warfarin-Associated Intracerebral Hemorrhage Protocol Reduces Timing of Door to Correction Interventions. [Journal Article]
- JNJ Neurosci Nurs 2019; 51(2):89-94
- CONCLUSIONS: Study findings support the hypothesis that the new protocol was associated with lower door-to-treatment times for eligible patients.
- Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. [Review]
- IJInt J Mol Sci 2019 Feb 19; 20(4)
- Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and m…
Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.
- Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. [Journal Article]
- AJAm J Clin Nutr 2019 Feb 01; 109(2):392-401
- CONCLUSIONS: The present study does not suggest that vitamin K intake influences the occurrence of total and advanced prostate cancer in the general US population.
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- Initial Assessment of Variability of Responses to Toxicants in Donor-Specific Endothelial Colony Forming Cells. [Journal Article]
- FPFront Public Health 2018; 6:369
- There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-formin…
There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-forming cells (ECFCs) isolated from blood would be highly useful for this purpose because these cells are involved in neonatal and adult vasculogenesis. We characterized the cytotoxicity of four known toxic chemicals (NaAsO2, CdCl2, tributyltin [TBT], and menadione) and their four relatively nontoxic counterparts (Na2HAsO4, ZnCl2, SnCl2, and phytonadione, respectively) in eight ECFC clones representing four neonatal donors (2 male and 2 female donors, 2 clones per donor). ECFCs were exposed to 9 concentrations of each chemical in duplicate; cell viability was evaluated 48 h later using the fluorescent vital dye fluorescent dye 5-Carboxyfluorescein Diacetate (CFDA), yielding concentration-effect curves from each experiment. Technical (day-to-day) variability of the assay, assessed from three independent experiments, was low: p-values for the differences of results were 0.74 and 0.64 for the comparison of day 2 vs. day 1 and day 3 vs. day 1, respectively. The statistical analysis used to compare the entire concentration-effect curves has revealed significant differences in levels of cytotoxicity induced by the toxic and relatively nontoxic chemical counterparts, demonstrating that donor-specific ECFCs can clearly differentiate between these two groups of chemicals. Partitioning of the total variance in the nested design assessed the contributions of between-clone and between-donor variability for different levels of cytotoxicity. Individual ECFC clones demonstrated highly reproducible responses to the chemicals. The most toxic chemical was TBT, followed by NaAsO2, CdCl2, and Menadione. Nontoxic counterparts exhibited low cytotoxicity at the higher end of concentration ranges tested. Low variability was observed between ECFC clones obtained from the same donor or different donors for CdCl2, NaAsO2, and TBT, but for menadione, the between-donor variability was much greater than the between-clone variability. The low between-clone variability indicates that an ECFC clone may represent an individual donor in cell-based assays, although this finding must be confirmed using a larger number of donors. Such confirmation would demonstrate that an in vitro ECFC-based testing platform can be used to characterize the inter-individual variability of neonatal ECFCs exposed to drugs and/or environmental toxicants.