The Disappearance of Heparin Activity with Liver Globulins and Determinations of Heparinase

1963 ◽  
Vol 10 (01) ◽  
pp. 071-080 ◽  
Author(s):  
L. B Jaques ◽  
C Mary Jaques
Keyword(s):  
Anticoagulant Activity ◽  
Rabbit Liver ◽  
Dissociation Curve ◽  
Ph Values ◽  
Phenol Extraction ◽  
Progressive Loss ◽  
Heparin Activity

SummaryPreparations were made of rabbit liver globulin by the method of Jaques for heparinase and their effect on heparin studied. The results confirmed the observations of a progressive loss of anticoagulant activity with globulin in 0.9% saline, of a loss of metachromatic activity after phenol extraction and the reversal of the latter by alkali. The latter observations were due to the solubility in phenol of heparin on combination with protein. With suitable preparations, a decrease in anticoagulant activity without decrease in metachromatic activity was observed, i.e. conversion of heparin to uroheparin. Loss of heparin due to combination with protein and resulting precipitation, solubility in phenol, etc. followed a protein pH-dissociation curve. Loss of heparin anticoagulant activity due to heparinase was maximal at pH 5.4. No loss of heparin occurred at pH values more acid than 5 or more alkaline than 7.

The Measurement of Heparin and Other Therapeutic Sufphated Polysaccharides in Plasma, Serum and Urine

1985 ◽  
Vol 54 (03) ◽  
pp. 630-634 ◽  
Author(s):  
J Dawes ◽  
C V Prowse ◽  
D D Pepper
Keyword(s):  
Biological Fluids ◽  
Anticoagulant Activity ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Heparin Therapy ◽  
Competitive Binding Assay ◽  
First Order Kinetics ◽  
Activity Measurements ◽  
Heparin Activity ◽  
Dose Dependent

SummaryThe competitive binding assay described will specifically and accurately measure concentrations of administered heparin in biological fluids with a sensitivity of 60 ng ml-1. Neither endogenous glycosaminoglycans, nor plasma proteins such as ATIII and PF4 interfere in the assay. Semi-synthetic highly sulphated heparinoids and LMW heparin can also be measured. Using this assay heparin clearance followed simple first-order kinetics over the dose range 100-5,000 units, but the half-life was strongly dose-dependent. There was good correlation with heparin activity measurements by APTT and anti-Xa clotting assays. Plasma concentrations were measurable for at least 5 h following subcutaneous injection of 10,000 units of heparin. Excretion in the urine could be followed after all but the lowest intravenous dose. This assay, used in conjunction with measurements of heparin anticoagulant activity, will be valuable in the elucidation of mechanisms of action of heparin and the heparinoids, and in the assessment and management of problems related to heparin therapy.

Disappearance Rate ot the Anticoagulant Effect of Heparin

1975 ◽  
Author(s):  
C.A.M. de Swart ◽  
A. Nijmeijer ◽  
J. W. N. Akkerman ◽  
J. J. Sixma
Keyword(s):  
Simple Technique ◽  
Single Injection ◽  
Anticoagulant Activity ◽  
Accurate Determination ◽  
Anticoagulant Effect ◽  
Disappearance Rate ◽  
Heparin Activity ◽  
Large Single Dose ◽  
Plasma Heparin

The disappearance of the anticoagulant activity of a intravenously administered well-defined commercial heparin was followed in human and dogs utilizing a diluted activated partial thromboplastin time (Marder) and an anti-Xa-assay (Tin). The anticoagulant activity was followed after the injection of a large single dose. More accurate determination of the relation between heparin level and disappearance rate was achieved by continuous infusion with different heparin dosages. The anticoagulant effect was linearly related with dosage administered above a certain minimum threshold. This is in agreement with disappearance curves obtained after a single injection that can be described by the formula:(in which S represents the heparin activity, K1 and K2 represent constants and K3 is the integration constant). References: Marder, V. J.: A simple technique for the measurement of plasma heparin concentration during anticoagulant therapy. Thromb. Diath. Haemorrh. 24, 230–239, 1970.Yin, E. T., Wessler, S.: Plasma heparin: A unique, practical, submicrogram sensitive assay. J. Lab. Clin. Med. 81, 298-310, 1973.

NEUTRALIZATION OF HEPARIN-LIKE SACCHARIDES BY COMPLEMENT S PROTEIN/VITRONECTIN

1987 ◽  
Author(s):  
D A Lane ◽  
A M Flynn ◽  
G Pejler ◽  
U Lindahl ◽  
K Preissner
Keyword(s):  
Heparan Sulfate ◽  
Anticoagulant Activity ◽  
Protein A ◽  
Membrane Attack Complex ◽  
Factor Xa ◽  
Molar Ratio ◽  
Platelet Factor ◽  
S Protein ◽  
Heparin Activity ◽  
Heparin Fractions

S protein, a major inhibitor of the assembly of the membrane attack complex of complement, has recently been shown to be identical to the serum spreading factor vitronectin. It has also been demonstrated to have anti-heparin properties. We have studied the heparin neutralizing properties of S protein/vitronectin using heparin, heparan sulfate and heparin oligosaccharides with high affinity for antithrombin. The ability of heparin fractions, Mr 7300-18800, and of the International Heparin Standard, to accelerate the inactivation of thrombin and Factor Xa by anti thrombin was readily neutralized by S protein/vitronectin. Addition of the protein to the various saccharide fractions at a molar ratio 1-3/1 produced 50/ neutralization, while complete neutralization was achieved at a molar ratio of <10/1. Moreover, S protein/vitronectin efficiently neutralized oligosaccharides of Mr 2400-7200, unlike the two other physiologically occur ing heparin neutralizing proteins histidine-rich glycoprotein <HRG) and platelet factor 4 < PF4) <Lane et al (1986) J. Biol. Chem.261, 3980; Lane et al (1984) Biochem. J. 218, 725). Like PF4, but unlike HRG, S protein/vitronectin readily neutralized the anticoagulant activities of heparan sulfate of Mr ˜20000. These findings indicate that S protein/vitronectin requires little more than the antithrombin-binding pentasaccharide with which to interact in order to express its anti-heparin activity. Furthermore, the results suggest that S protein/vitronectin may be a physiological1y important modulator of the anticoagulant activity of heparin-like material on or near the vascular endothelium.

High Affinity Binding of Heparin by Necrotic Tumour Cells Neutralises Anticoagulant Activity

2001 ◽  
Vol 86 (08) ◽  
pp. 616-622 ◽  
Author(s):  
Sumihito Morita ◽  
Milena Gebska ◽  
Ajay Kakkar ◽  
Michael Scully
Keyword(s):  
Ribosomal Proteins ◽  
Anticoagulant Activity ◽  
Heparan Sulphate ◽  
Live Cells ◽  
Affinity Binding ◽  
Heparin Binding ◽  
Pancreatic Carcinoma Cell Line ◽  
High Affinity Binding ◽  
High Affinity ◽  
Heparin Activity

SummaryWe have observed a striking neutralisation of the anticoagulant activity of unfractionated heparin in the presence of a pancreatic carcinoma cell line (MIA PaCa-2) due to binding of around 9 g of heparin per 107 cells (apparent Kd, 30 nM). The loss of anticoagulant activity was less marked in the presence of low molecular weight forms of heparin. Binding to the cell blocked acceleration of the thrombin:anti-thrombin interaction by heparin. Neutralisation of heparin activity was also shown to occur in the presence of a number of other tumour cell lines. FACS analysis demonstrated that live cells did not bind heparin and high affinity binding only occurred to dead MIA PaCa-2 cells. Heparin binding proteins accumulating in cell medium were identified as histone and ribosomal proteins that will become exposed during necrosis. The release of these proteins from cells within the necrotic core of a tumour or from cells killed during chemotherapy may abrogate the heparan sulphate/antithrombin system and possibly contribute to the idiopathic thromboembolism often associated with cancer (Trousseau’s syndrome). The findings also suggest a reason for the reported advantage of LMWH over UFH in treating venous thromboembolism in cancer patients and in improving patient survival.

Ultrastructural investigation of an adenoma of the pituitary post mortem

1987 ◽  
Vol 45 ◽  
pp. 622-623
Author(s):  
Shirley Siew ◽  
W. C. deMendonca
Keyword(s):  
Deleterious Effect ◽  
Anterior Lobe ◽  
Definitive Diagnosis ◽  
Pars Intermedia ◽  
Post Mortem ◽  
Close Apposition ◽  
Autopsy Material ◽  
Progressive Loss ◽  
Transmission Electron ◽  
Means Of Transmission

The deleterious effect of post mortem degeneration results in a progressive loss of ultrastructural detail. This had led to reluctance (if not refusal) to examine autopsy material by means of transmission electron microscopy. Nevertheless, Johannesen has drawn attention to the fact that a sufficient amount of significant features may be preserved in order to enable the establishment of a definitive diagnosis, even on “graveyard” tissue.Routine histopathology of the autopsy organs of a woman of 78 showed the presence of a well circumscribed adenoma in the anterior lobe of the pituitary. The lesion came into close apposition to the pars intermedia. Its architecture was more compact and less vascular than that of the anterior lobe. However, there was some grouping of the cells in relation to blood vessels. The cells tended to be smaller, with a higher nucleocytoplasmic ratio. The cytoplasm showed a paucity of granules. In some of the cells, it was eosinophilic.

Evaluation of dissolution properties of silymarin capsules at different pH values

Planta Medica ◽  
2013 ◽  
Vol 79 (13) ◽  
Author(s):  
A Uzunovic ◽  
S Pilipovic ◽  
A Elezovic ◽  
A Sapcanin ◽  
O Rahic
Keyword(s):  
Ph Values ◽  
Dissolution Properties

Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

1999 ◽  
Vol 82 (11) ◽  
pp. 1462-1468 ◽  
Author(s):  
José Fernández ◽  
Jari Petäjä ◽  
John Griffin
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Protein C ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor V ◽  
Factor Va ◽  
Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

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