Antithrombotic and Anticoagulant Activities of a Low Molecular Weight Fucoidan by the Subcutaneous Route

1999 ◽  
Vol 81 (03) ◽  
pp. 391-395 ◽  
Author(s):  
S. Colliec Jouault ◽  
S. Mauray ◽  
J. Theveniaux ◽  
C. Sternberg ◽  
Boisson Vidal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Subcutaneous Injection ◽  
Thrombin Generation ◽  
Sulfated Polysaccharides ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Antithrombotic Activity ◽  
Single Subcutaneous Injection ◽  
Chemical Structures

SummaryFucoidans (high-molecular-weight sulfated polysaccharides extracted from brown seaweeds) have anticoagulant and antithrombotic effects. They inhibit thrombin by catalyzing both serpins (antithrombin and heparin cofactor II) according to their chemical structures and origins. In this study, a low-molecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant activities of this new compound were compared to those of a low-molecular-weight heparin (LMWH), dalteparin, following subcutaneous administration to rabbits. This LMW fucoidan exhibited dose-related venous antithrombotic activity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection. Its activity was comparable to that of dalteparin (close to 200 anti-Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but disappeared by 8 h. The antithrombotic activity was not associated with either a prolongation of the thrombin clotting time (TCT) or an increase in anti-Xa activity, contrary to dalteparin. A slight prolongation of APTT occurred with both compounds. This venous antithrombotic activity was associated with a decrease in ex vivo thrombin generation and with a significant increase in the lag phase in a thrombin generation test. LMW fucoidan thus has potent antithrombotic activity and a potentially weaker haemorrhagic effect (i.e. a smaller effect on coagulation tests and a smaller prolongation of the bleeding time) than dalteparin.

INFLUENCE OF THE SULFATION PATTERN ON CERTAIN BIOLOGICAL PROPERTIES OF GALACTOSAMINOGLYCANS

1987 ◽  
Author(s):  
B Casu ◽  
L Marchese ◽  
A Naggi ◽  
G Torri ◽  
J Fareed ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Chlorosulfonic Acid ◽  
Biological Properties ◽  
Sulfated Polysaccharides ◽  
Low Molecular Weight ◽  
Antithrombotic Activity

In order to investigate the influence of charge distribution and chain length on the biological properties of sulfated polysaccharides, additional sulfate groups were introduced into the galactosaminoglycans, chondriotin sulfate and dermatan sulfate. Using a flexible method (with sulfuric acid and chlorosulfonic acid) for concurrent sulfation and controlled depolymerization, numerous products were obtained and characterized by chemical, enzymatic and nuclear magnetic resonance spectroscopic methods. The biologic actions of these products were profiled in both in vitro and in vivo assays for antithrombotic activity. Despite a weaker in vitro anticoagulant activity, low molecular weight over sulfated galactosaminoglycans produced significant dose-dependent antithrombotic actions in animal models which were similar to the actions observed with oversulfated low molecular weight heparins. These results suggest that a significant antithrombotic activity can be elicited through non-specific interactions of polysulfates with cellular and plasma components, and that clusters of sulfate groups such as the 4-6 disulfate group on D-galactosaminoglycan residues may be important for these interactions. Furthermore, these results, also suggest that supersulfation of glycosaminogly-cans results in products with biologic activity distinct from the native material.

FRACTIONATION OF LIVER SOMATOMEDIN ACTIVITY BY ULTRAFILTRATION

1974 ◽  
Vol 62 (2) ◽  
pp. 355-361 ◽  
Author(s):  
JENNIFER M. DEHNEL ◽  
P. D. McCONAGHEY ◽  
M. J. O. FRANCIS
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Weight Fraction ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Cartilage Growth ◽  
The Relationship ◽  
Somatomedin Inhibitors

SUMMARY Plasma somatomedin is the intermediary through which growth hormone (GH) exerts its effects on the growing skeleton. Somatomedin activity may be produced in vitro by perfusion of the liver and kidneys of rats with Waymouth's medium containing GH. The relationship between the activity of plasma somatomedin and somatomedin of hepatic and renal origin has yet to be clarified. Somatomedin from plasma can be separated into active fractions of both high and low molecular weight. Similarly, ultrafiltration of medium containing somatomedin of hepatic origin indicates the existence of two active fractions, one of high molecular weight (greater than 50000) and one of low molecular weight (less than 1000). The latter can be attributed to the release of amino acids, such as serine and glutamine, by the perfused tissue. The high molecular weight fraction is believed to represent GH-dependent somatomedin. Fractions that inhibit production of cartilage matrix are present in liver perfusates as well as in plasma. These results provide further evidence that the liver is a source of GH-dependent somatomedin in vivo. Furthermore, cartilage growth may be controlled not only by the GH-stimulated release of somatomedin by the liver, but also by its release of acid-labile somatomedin inhibitors.

Four Heparin Preparations: Anti-Xa Potentiating Effect of Heparin after Subcutaneous Injection

1976 ◽  
Vol 35 (03) ◽  
pp. 586-591 ◽  
Author(s):  
E. A Johnson ◽  
T. B. L Kirkwood ◽  
Yvonne Stirling ◽  
J. L Perez-Requejo ◽  
G. I. C Ingram ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Randomized Trial ◽  
High Molecular Weight ◽  
Subcutaneous Injection ◽  
Low Molecular Weight ◽  
Mean Values ◽  
Sodium Heparin ◽  
Calcium Heparin ◽  
Mean Molecular Weight ◽  
Plasma Heparin

SummaryFour different heparin preparations - sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m. w. 9,000) and high molecular weight sodium heparin (mean m. w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i. u./ml) at 3-4 hours after the injection. With sodium heparin (m. w. 15,000) the highest values (0.135 i. u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0. 072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 1. u./ml at 3-4 hours after injection).These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

scholarly journals Enoxaparin is a low-molecular-weight heparin with a complex chemical structure and various non-anticoagulant properties

2016 ◽  
Vol 88 (12) ◽  
pp. 109-115
Author(s):  
S K Zyryanov ◽  
E A Ushkalova
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Chemical Structure ◽  
Complex Structure ◽  
Low Molecular Weight ◽  
Antithrombotic Activity ◽  
Complex Chemical ◽  
Chemical Structures ◽  
Standard Distribution

The paper discusses the non-anticoagulant properties of unfractionated heparin and enoxaparin and their relation to their chemical structures. It is emphasized that enoxaparin has multiple, often interrelated, non-anticoagulant effects that can complement its antithrombotic activity and enhance the efficiency of therapy in patients receiving the drug for various indications. The realization of these effects requires the complex structure with the standard distribution of molecular weight (Mw) (average Mw, about 4500 Da, as well as Mw of less than 2000 Da (68%), and more than 8000 Da (

scholarly journals Molluscicidal Polyphenols from Species of Fucaceae

2008 ◽  
Vol 3 (2) ◽  
pp. 1934578X0800300
Author(s):  
Asmita V. Patel ◽  
David C. Wright ◽  
Maricela Adrian Romero ◽  
Gerald Blunden ◽  
Michael D. Guiry
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Algal Species ◽  
Weight Fraction ◽  
The Other ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Bifurcaria Bifurcata ◽  
Marine Algal ◽  
Molluscicidal Activity

The aqueous fractions of the dry methanol extracts (500 ppm) of sixty marine algal species were screened for molluscicidal activity against Biomphalaria glabrata, which is an important host of the bilharzia-causing Schistosoma species. The majority of the extracts tested were inactive at the concentration used, but those of Fucus serratus, F. vesiculosus, Pelvetia canaliculata, Ascophyllum nodosum, Halidrys siliquosa, Bifurcaria bifurcata, Dictyota dichotoma and Halopithys incurva all showed significant molluscicidal activity. Treatment with polyvinylpolypyrrolidone (PVPP) either removed or drastically reduced the activity of the extracts of F. serratus, F. vesiculosus, P. canaliculata, A. nodosum, Halidrys siliquosa and Halopithys incurva, which suggested that the active compounds in the extracts of these species were polyphenolic in nature. The active extracts of the other two seaweed species did not appear to be affected by treatment with PVPP. Dialysis of the active extracts against distilled water separated them into high and low molecular weight fractions. In the case of the two Fucus species, P. canaliculata and A. nodosum, the activity resided in the high molecular weight fraction, whereas with all the other species, the activity was found in the low molecular weight fraction. 1H NMR spectroscopic examination of the active extracts confirmed that the molluscicidal components of the extracts of the Fucus species, P. canaliculata and A. nodosum were high molecular weight polyphenols.

Cartilage fucoproteins with sites for cross-linking by transglutaminase

1987 ◽  
Vol 65 (4) ◽  
pp. 280-285 ◽  
Author(s):  
J. Michael Bowness
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
High Performance ◽  
Specific Activity ◽  
Weight Fraction ◽  
Dry Weight ◽  
Insoluble Fraction ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Collagen Iii

Slices of various types of cartilage were incubated with either L-[6-3H]fucose or [1,4-3H(N)]putrescine. Homogenization of the slices and fractionation of the homogenates showed for both labels that an insoluble collagenase-resistant fraction had the highest specific activity (dpm/mg dry weight). Examination of an exhaustive proteolytic digest of this insoluble fraction by ion-exchange high performance liquid chromatography showed the presence of γ-glutamyl[3H]putrescine. Chromatography of solubilized [3H]fucoprotein fractions showed the presence of several low molecular weight peaks, as well as high molecular weight material. Incubation of [3H]fucoprotein extracts with transglutaminase increased the high molecular weight peaks and decreased the low molecular weight ones. Incubation of the cartilage slices with L-[3H]fucose plus 0.5 mM dansylcadaverine, an inhibitor of transglutaminase, caused a decrease in the insoluble and high molecular weight fraction relative to the low molecular weight peaks. It is hypothesized that this is due to inhibition of cross-link formation between fucoprotein components of the cartilage which are transglutaminase substrates. One major low molecular weight peak, which labels with both fucose and putrescine, corresponds in size with the 15 000 subunit of collagen III aminopropeptide, which is known to be a substrate for transglutaminase.

scholarly journals The Antiproliferative Activity of Sclerotia ofLignosus rhinocerus(Tiger Milk Mushroom)

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
M. L. Lee ◽  
N. H. Tan ◽  
S. Y. Fung ◽  
C. S. Tan ◽  
S. T. Ng
Keyword(s):  
Molecular Weight ◽  
Cancer Cells ◽  
High Molecular Weight ◽  
Antiproliferative Activity ◽  
Human Lung ◽  
Weight Fraction ◽  
Low Molecular Weight ◽  
Cytotoxic Action ◽  
High Molecular Weight Fraction ◽  
Human Breast

Lignosus rhinocerus, the tiger milk mushroom, is one of the most important medicinal mushrooms used by the indigenous people of Southeast Asia and China. It has been used to treat breast cancer. A cold water extract (LR-CW) prepared from the sclerotia ofL. rhinoceruscultivar was found to exhibit antiproliferative activity against human breast carcinoma (MCF-7) and human lung carcinoma (A549), withIC50of 96.7 μg/mL and 466.7 μg/mL, respectively. In comparison, LR-CW did not show significant cytotoxicity against the two corresponding human normal cells, 184B5 (human breast cell) and NL 20 (human lung cell). DNA fragmentation studies suggested that the cytotoxic action of LR-CW against cancer cells is mediated by apoptosis. Sephadex G-50 gel filtration fractionation of LR-CW yielded a high-molecular-weight and a low-molecular-weight fraction. The high-molecular-weight fraction contains mainly carbohydrate (68.7%) and small amount of protein (3.6%), whereas the low-molecular-weight fraction contains 31% carbohydrate and was devoid of protein. Only the high-molecular-weight fraction exhibited antiproliferative activity against cancer cells, withIC50of 70.0 μg/mL and 76.7 μg/mL, respectively. Thus, the cytotoxic action of the LR-CW is due to the high-molecular-weight fraction, either the proteins or protein-carbohydrate complex.

Tumor Uptake of High and Low Molecular Weight Fractions from 67Ga-Citrate Labelled Blood Plasma

1984 ◽  
Vol 23 (02) ◽  
pp. 59-61 ◽  
Author(s):  
M. C. Crone ◽  
P. Thouvenot ◽  
F. Brunotte ◽  
C. Marchai ◽  
J. Robert ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Blood Plasma ◽  
High Molecular Weight ◽  
Gel Filtration ◽  
Weight Fraction ◽  
Blood Protein ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
67Ga Citrate

SummaryBlood plasma from tumor-bearing rats was incubated with 67Ga-citrate, and two fractions of high molecular weight (proteins) and low molecular weight were isolated by dialysis and by gel-filtration chromatography. Both fractions showed a different in vivo uptake by DS-sarcoma-bearing animals, the high molecular weight fraction being accumulated to a lesser extent. Compared to 67Ga-citrate the low molecular weight fraction showed a different uptake which for most tissues was significatively higher. This behavior suggests the presence of 67Ga in chemical forms other than citrate in the low molecular weight fraction. The lower uptake of the blood protein fraction is discussed.

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