Metabolic Studies of Vitamin K1-14C and Menadione-14C in the Normal and Hepatectomized Rats

1968 ◽  
Vol 19 (03/04) ◽  
pp. 383-388 ◽  
Author(s):  
R Losito ◽  
C. A Owen ◽  
E. V Flock ◽  
Keyword(s):  
Enzymatic Hydrolysis ◽  
Oral Anticoagulants ◽  
Urinary Metabolites ◽  
The Other ◽  
Vitamin K1 ◽  
Vitamin K3 ◽  
Metabolic Studies ◽  
Intact Rats

SummaryThe metabolism of vitamin K1- 14C and menadione-14C (vitamin K3-14C) was studied in normal and hepateetomized rats. After the administration of menadione, about 70% of the 14C was excreted in the urine in 24 hrs in both types of rats. Two urinary metabolites were identified by enzymatic hydrolysis: one a glucuronide and the other a sulfate of reduced menadione. Thus, the liver is not necessary for the metabolism of menadione. In the vitamin K1 studies, the intact rats excreted only 10% of the 14C and the hepatectomized rats excreted less than 0.5%. The retention of vitamin K1 may explain its superiority over menadione as an antidote for overdosages of oral anticoagulants.

Multi-Center Study of Thromboplastin Calibration Precision – Influence of Reagent Species, Composition, and International Sensitivity Index (ISI)

1993 ◽  
Vol 69 (01) ◽  
pp. 035-040 ◽  
Author(s):  
A M H P van den Besselaar ◽  
R M Bertina
Keyword(s):  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
The Other ◽  
World Health ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Bovine Plasma ◽  
Significant Difference ◽  
The Mean ◽  
International Sensitivity Index

SummaryFour thromboplastin reagents were tested by 18 laboratories in Europe, North-America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W. H. O.).The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)?The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest interlaboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.The mean ISI values calculated with OBT/79 and CRM 149R were practically identical, indicating that there is no bias in the ISI of these reference preparations and that these reference preparations have been stable since their original calibration studies in 1979 and 1987, respectively.International Normalized Ratio (INR) equivalents were calculated for a lyophilized control plasma derived from patients treated with oral anticoagulants. There were small but significant differences in the mean INR equivalents between the bovine and rabbit thromboplastins. There were no differences in the interlaboratory variation of the INR equivalents, when the four thromboplastins were compared.

Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

2009 ◽  
Vol 297 (6) ◽  
pp. C1358-C1367 ◽  
Author(s):  
Gerald J. Atkins ◽  
Katie J. Welldon ◽  
Asiri R. Wijenayaka ◽  
Lynda F. Bonewald ◽  
David M. Findlay
Keyword(s):  
Bone Formation ◽  
Vitamin K ◽  
Type I Collagen ◽  
Vitamin K2 ◽  
Type I ◽  
Vitamin K1 ◽  
Vitamin K3 ◽  
Positive Effect

The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that γ-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-κB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.

NOTES ON THE PREPARATION AND USE OF 14C-LABELLED VITAMIN K1 AND VITAMIN K3

1957 ◽  
Vol 35 (8) ◽  
pp. 941-943 ◽  
Author(s):  
R. J. Woods ◽  
J. D. Taylor
Keyword(s):  
Vitamin K1 ◽  
Vitamin K3

not available

scholarly journals Two Types of Prothrombin in Vitamin K Deficiency

1970 ◽  
Vol 23 (03) ◽  
pp. 633-637 ◽  
Author(s):  
H. C Hemker ◽  
Annemarie D. Muller ◽  
E. A Loeliger
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Coagulation Factors ◽  
The Other ◽  
Vitamin K Deficiency ◽  
Two Stage ◽  
K Deficiency

SummaryIn vitamin K deficiency (either absolute or induced by oral anticoagulants) two types of prothrombin occur. One is not distinguishable from normal prothrombin. It generates thrombin quickly in a medium in which the factors V, VII and X, thromboplastin and Ca++ are present in sufficient amounts. The other is converted into thrombin much more slowly under the same conditions. In the onestage prothrombin assay only the first form is measured, in a two-stage prothrombin assay both forms are estimated. This accounts for the well-known discrepancy between these two tests in vitamin K deficiency. The abnormal prothrombin can be considered one of the Proteins Induced by Vitamin K Absence. The occurrence of this kind of proteins fits in the concept of the action of vitamin K as a co-factor in a system that converts polypeptide-precursors into coagulation factors.

THE EFFECT OF ADRENALECTOMY, DIHYDROERGOTAMINE, AND DIBENZYLINE ON THE SENSITIVITY OF RATS TO TOLBUTAMIDE

1963 ◽  
Vol 41 (10) ◽  
pp. 2189-2195 ◽  
Author(s):  
Rosemary D. Hawkins ◽  
R. E. Haist
Keyword(s):  
Blood Glucose ◽  
The Other ◽  
Compensatory Mechanisms ◽  
Blood Samples ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Significant Difference ◽  
Tail Blood ◽  
Adrenalectomized Rats ◽  
Intact Rats

In the rat, the magnitude of the hypoglycaemic response to a dose of tolbutamide (50 mg/kg per os) which does not depress blood glucose levels to the point where adrenal compensatory mechanisms are stimulated is unaffected by adrenalectomy. On the other hand, when a dose is given which induces a greater hypoglycaemia (100 mg/kg per os) a very significant difference between adrenalectomized and sham-operated animals is observed, the adrenalectomized rats displaying a far greater sensitivity to the hypoglycaemic action of this compound. In intact rats, the hypoglycaemia induced by tolbutamide (100 mg/kg per os) is lessened by pretreatment of the animals with Dibenzyline (4 mg/kg) but enhanced by the prior injection of dihydroergotamine (2 mg/kg). Larger doses of dihydroergotamine alone cause a reduction in glucose levels of tail blood which is greater than that found in carotid blood samples withdrawn at the same times.

scholarly journals Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

2016 ◽  
Vol 5 (2) ◽  
pp. 102 ◽  
Author(s):  
Marco Alings ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
The Other ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Phase Iii Clinical Trials ◽  
Dosing Regimens

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACs: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACs offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACs should be considered in at-risk patient populations.

scholarly journals Familial protein S deficiency with a variant protein S molecule in plasma and platelets

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 213-221 ◽  
Author(s):  
HP Schwarz ◽  
MJ Heeb ◽  
R Lottenberg ◽  
H Roberts ◽  
JH Griffin
Keyword(s):  
Gene Expression ◽  
Family Member ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Protein S ◽  
The Other ◽  
Protein S Deficiency ◽  
Functional Protein ◽  
S Deficiency ◽  
Variant Protein

Abstract A protein S deficient family presenting a variant protein S molecule in plasma and platelets is described. The propositus, age 20, and two brothers suffered from venous thrombotic disease. The propositus, the only family member studied while taking oral anticoagulants, had a protein S antigen (ag) level of 17% and undetectable activity. As demonstrated by immunoblotting both the propositus and one clinically affected brother (42% ag, 7% activity) presented variant protein S molecules of 65,000 molecular weight (mol wt) while the other clinically affected brother (64% ag, 11% activity) had only protein S with normal electrophoretic mobility of 70,000 mol wt. The mother had normal protein S levels (93% ag, 100% activity) but had both normal and variant protein S molecules and based on her functional protein S data a normal anticoagulant activity of the variant molecule is suggested. One asymptomatic but protein S deficient sister (68% ag, 9% activity) as well as the asymptomatic protein S deficient father (59% ag, 10% activity) had only protein S molecules of 70,000 mol wt. The variant protein S bound to C4b-binding protein in plasma, and differed from normal protein S in carbohydrate content. Platelets of each family member contained the same immunoblotting pattern of normal and variant protein S forms as found in plasma, consistent with the hypothesis that protein S gene expression involves codominant expression of two alleles that is similar in cells that control the synthesis of both platelet and plasma forms of protein S.

METABOLISM OF [4-14C]LYNESTRENOL IN MAN

1968 ◽  
Vol 42 (2) ◽  
pp. 337-343 ◽  
Author(s):  
SORAYA KAMYAB ◽  
K. FOTHERBY ◽  
A. I. KLOPPER
Keyword(s):  
Phenolic Compounds ◽  
Enzymatic Hydrolysis ◽  
Half Life ◽  
Human Subjects ◽  
Free Fraction ◽  
Urinary Metabolites ◽  
Polar Compounds ◽  
Mean Value ◽  
Biological Half Life ◽  
Chromatographic Evidence

SUMMARY After the administration of [4-14C]lynestrenol (17α-ethynyl-19-nor-androst-4-en-17β-ol) to 7 human subjects 31·–57·6% of the dose, whether administered orally or i.v., was excreted in the urine within 5 days. The biological half-life of radioactivity was 26·5 hr. After acid and enzymatic hydrolysis, 58·7 and 45·6% respectively of the urinary radioactivity was extractable. About 10% of the urinary metabolites were excreted as sulphate conjugates. A mean value of 1·75% of the administered dose was converted to phenolic compounds. The metabolites in the free fraction and enzymehydrolysed extract of urine were almost entirely polar compounds, whereas 70% of the metabolites in the sulphate fraction were much less polar. The chromatographic evidence showed that hydroxylation of lynestrenol must have occurred at two points in the molecule. Plasma radioactivity decreased more rapidly than after administration of norethisterone.

scholarly journals Metabolic studies on CS-359, a new .BETA.-adrenergic blocking agent. I. Isolation and identification of the urinary metabolites of CS-359.

1975 ◽  
Vol 23 (6) ◽  
pp. 1173-1183
Author(s):  
RYOZO HAYASHI ◽  
MINORU OKADA ◽  
TADAMASA NAKAZAWA ◽  
YORIHISA TANAKA ◽  
YASUO SHIMOJI ◽  
...  
Keyword(s):  
Urinary Metabolites ◽  
Blocking Agent ◽  
Isolation And Identification ◽  
Beta Adrenergic ◽  
Metabolic Studies ◽  
Adrenergic Blocking

METABOLISM OF OESTRIOL-3-SULPHATE-16-GLUCOSIDURONATE IN PREGNANT WOMEN

1968 ◽  
Vol 59 (4) ◽  
pp. 595-610 ◽  
Author(s):  
U. Goebelsmann ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Gastrointestinal Tract ◽  
Urinary Excretion ◽  
General Scheme ◽  
Urinary Metabolites ◽  
The Other ◽  
Missed Abortion ◽  
Pregnancy Urine ◽  
Relationship Of ◽  
The Relationship ◽  
Important Constituent

ABSTRACT A combination of 3H-labelled oestriol-3-sulphate-16-glucosiduronate (OE3-3S,16Gl) and 14C-labelled oestriol-16-glucosiduronate (OE3-16Gl) was infused over a 6 hour period to one woman at midpregnancy and to another woman with missed abortion in the 4th month of gestation. The urinary metabolites were isolated and identified. Sixty-four per cent of the 3H- and about 80 % of the 14C-labelled material was excreted in the urine within 24 hours. Some 20 % of the 3H-labelled, but only 2–3 % of the 14C-labelled material recovered was OE3-3S,16Gl. Approximately one half of the 3H-, but less than one-third of the 14C-labelled material was oestriol-3-glucosiduronate (OE3-3Gl). On the other hand, more than two-thirds of the 14C-labelled material, but less than one-third of the 3H-labelled was OE3-16Gl. The urinary elimination of OE3-3S,16Gl was much slower than that of OE3-16Gl and resembled closely the behaviour of oestriol-3-sulphate (OE3-3S) in this respect. The amounts of endogenous OE3-3S,16Gl and OE3-16Gl reaching the circulation each hour were calculated from their urinary excretion and from the relationship of infused and excreted labelled OE3-3S,16Gl and OE3-16Gl. On the basis of these estimates it is concluded that OE3-3S,16Gl is a quantitatively important constituent of pregnancy plasma, but not of pregnancy urine. It is suggested that OE3-3S,16Gl is formed mainly, if not entirely from OE3-16Gl, most probably in the liver and perhaps also in the gastrointestinal tract. A general scheme is presented, describing the over-all metabolism of conjugated oestriol.

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