scholarly journals No evidence for vitamin K-dependent carboxylation of canine surfactant apoproteins, 28-36 kDa

1988 ◽  
Vol 252 (3) ◽  
pp. 851-856 ◽  
Author(s):  
R Wallin ◽  
M Seaton ◽  
L F Martin

Recent research has shown that rat surfactant apoproteins (26-38 kDa) are vitamin K-dependent [Rannels, Gallaher, Wallin & Rannels (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5952-5956]. We have investigated the effect of the vitamin K antagonist warfarin on this family of apoproteins in surfactant from dog lung. Our data suggest that warfarin does not interfere with synthesis and secretion of these proteins into dog lung surfactant. Abnormal surfactant apoproteins, produced in response to warfarin treatment of the dog, were also not found in lung surfactant. 4-Carboxyglutamic acid analysis of purified dog apoproteins also failed to detect the vitamin K-modification. When vitamin K-dependent 14C labelling of precursors of vitamin K-dependent proteins was carried out, fluorography of these precursors, when electrophoresed into SDS/polyacrylamide gels, revealed 14C-labelled proteins of apparent molecular mass 74, 46, 42, 34, 31 and 23 kDa. Antibodies produced against purified dog surfactant apoproteins recognized precursors of the surfactant apoproteins in lung microsomes but did not recognize any 14C-labelled carboxylase substrates. These precursors appeared on immunoblots with apparent molecular mass 29, 32, 33 and 50 kDa. Our data suggest that there are significant differences between this class of surfactant apoproteins in the rat and the dog.

2020 ◽  
Vol 68 (2) ◽  
Author(s):  
Silvio Romano ◽  
Elisa Salustri ◽  
Antonio G. Robles ◽  
Leonardo Calò ◽  
Maria Penco ◽  
...  

2020 ◽  
Vol 26 (23) ◽  
pp. 2686-2691 ◽  
Author(s):  
Ioannis Doundoulakis ◽  
Christina Antza ◽  
Haralambos Karvounis ◽  
George Giannakoulas

Background: Anticoagulation in patients with pulmonary embolism. Objective: To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism. Methods: We performed a systematic search of systematic reviews via multiple electronic databases from inception to August 19th, 2019, without language restriction. Two authors independently extracted data and assessed the methodological quality of the included systematic reviews using the ROBIS tool. Results: We found twelve systematic reviews. Eleven SRs collected their data from randomized clinical trials and one from observational studies. All the included studies were published between 2014 and 2019 in English. The methodological quality of the 12 systematic reviews was low to high. None of the systematic reviews, which are included in our overview of systematic reviews, has evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. Conclusion: This is the first effort to summarize evidence about non-vitamin K antagonist oral anticoagulants in an overview of systematic reviews focusing exclusively on patients with pulmonary embolism. The evidence suggests that the non-vitamin K antagonist oral anticoagulants seem to be more effective and safer than a dualdrug approach with LMWH- VKA.


2021 ◽  
Vol 80 (5) ◽  
pp. 598-604
Author(s):  
Cindy G Boer ◽  
Ingrid Szilagyi ◽  
N Long Nguyen ◽  
Tuhina Neogi ◽  
Ingrid Meulenbelt ◽  
...  

ObjectivesVitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.MethodsWe investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association.ResultsAcenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94–3.20), both for knee (OR=2.34, 95% CI=1.67–3.22) and hip OA (OR=2.74, 95% CI=1.82–4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69–6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78–1.33).ConclusionsThese findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Manzo-Silberman ◽  
T Chouihed ◽  
L Fraticelli ◽  
A Peiretti ◽  
C Claustre ◽  
...  

Abstract Introduction Atrial Fibrillation (AF) is the most common arrythmia, especially in older adults. AF represents 1% of emergency department (ED) visits a third of which are de novo or recurrent. While the diagnosis is given quickly by reading the electrocardiogram (ECG), its management both remains complex. European guidelines have been published in 2016. Purpose Our study aimed to investigate guidelines implementation in French ED. Methods Prospective national multicenter study (clinical trials NCT 03836339) and core interpretation of ECG. Consecutive patients admitted in 32 French ED for AF confirmed by ECG were prospectively included. Clinical characteristics at admission were recorded by the physician. The 3-months telephone follow-up was ensured by one operator. Results From 1/10/2018 to 30/11/2018, 1369 patients with AF were included, of whom 295 (21.55%) had a de novo AF. Patients were 80 [65; 87] years old, 51.17% of men, 71.53% self-ruling, 91.53% living at home, 65.42% transported by firemen or by ambulances and 4,07% by a mobile intensive care unit. Twenty-six (8.84%) patients had a history of stroke or transient ischemic stroke and none of them on anticoagulants. CHA2DS2-VASC score was performed in 66.78% of patients and was 0 in 14 (7.11%) patients. HAS-BLED score = 2 [1; 3]. At admission 50.17% of patients received anticoagulants, of whom 49.32% a non-vitamin K antagonist oral anticoagulant, 0.68% Vitamin K antagonists, 50.68% UFH or LMWH. Beta-blockers were administered in 102 (24.01%) patients and amiodarone in 38 (12.89%). Cardiac echography has been performed in 20.34% of patients. Atrial fibrillation was the primary diagnosis in 42.71% of patients. It has been associated to a pneumopathy in 25.17% of patients, a pulmonary embolism in 4.76% and acute alcoholism in 1.36% of them. Precipitating factor was often undetermined. The discharge to the home concerned 18.64% of patients, 26.78% of patients were hospitalized in ED hospitalization unit, 23.05% in cardiology or intensive care unit. At 3 months, 49% of patients were on anticoagulants, of whom 90% on non-vitamin K antagonist oral anticoagulants, 95% of them didn't report any bleeding event and 41.77% of them were able to have a cardiology consultation within three months. Three-months mortality was about 22.09%, and rehospitalization rate about 22.89%. Conclusion It seems to be a reticence to initiate anticoagulation of patients admitted to ED with a de novo AF. It could be explained by both the advanced age of the patients and the lack of an organized access to a systematic cardiology consultation at discharge. Patients with chronic AF are subject to high mortality at 3 months and a significant risk of readmission. The application of the guidelines could be optimized by a better training program and the implementation of a dedicated pathway of care. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer


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