scholarly journals In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga Fucus evanescens

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 577
Author(s):  
Natalia V. Krylova ◽  
Artem S. Silchenko ◽  
Anastasia B. Pott ◽  
Svetlana P. Ermakova ◽  
Olga V. Iunikhina ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Vero Cells ◽  
Low Molecular Weight ◽  
Focus Formation ◽  
Adsorption Activity ◽  
Fucus Evanescens ◽  
Virus Attachment ◽  
Main Component ◽  
Molecular Weight Fractions

The Hantaan orthohantavirus (genovariant Amur–AMRV) is a rodent-borne zoonotic virus; it is the causative agent of haemorrhagic fever with renal syndrome in humans. The currently limited therapeutic options require the development of effective anti-orthohantavirus drugs. The ability of native fucoidan from Fucus evanescens (FeF) and its enzymatically prepared high-molecular-weight (FeHMP) and low-molecular-weight (FeLMP) fractions to inhibit different stages of AMRV infection in Vero cells was studied. The structures of derivatives obtained were determined using nuclear magnetic resonance (NMR) spectroscopy. We found that fucoidan and its derivatives exhibited significant antiviral activity by affecting the early stages of the AMRV lifecycle, notably virus attachment and penetration. The FeHMP and FeLMP fractions showed the highest anti-adsorption activity by inhibiting AMRV focus formation, with a selective index (SI) > 110; FeF had an SI of ~70. The FeLMP fraction showed a greater virucidal effect compared with FeF and the FeHMP fraction. It was shown by molecular docking that 2O-sulphated fucotetrasaccharide, a main component of the FeLMP fraction, is able to bind with the AMRV envelope glycoproteins Gn/Gc and with integrin β3 to prevent virus–cell interactions. The relatively small size of these sites of interactions explains the higher anti-AMRV activity of the FeLMP fraction.

scholarly journals Anticoagulant Activities of Lung and Mucosal Heparin

1977 ◽  
Author(s):  
T. W. Barrowcliffe ◽  
E. A. Johnson ◽  
C. A. Eggleton ◽  
D. P. Thomas
Keyword(s):  
Molecular Weight ◽  
Antithrombin Iii ◽  
Gel Filtration ◽  
High Ratio ◽  
Low Molecular Weight ◽  
Multiple Role ◽  
Heparin Activity ◽  
Molecular Weight Fractions

Interaction with antithrombin III is thought to be the main mechanism whereby heparin exerts an anticoagulant effect, but measurements of this specific heparin activity by an anti-Xa assay do not always agree with measurements made by ‘multiple role’ assays, such as APTT or pharmacopoeial assays. Two batches of lung heparin had APTT activities in vitro about 1.4 times those found by anti-Xa, whereas in several batches of porcine mucosal heparin this ratio was about 0.8. All assays by both methods were carried out against the 3rd International Standard for heparin. After gel filtration, lung heparin maintained a high ratio of APTT to anti-Xa activity in all except the low molecular weight fractions, where the two activities were both about 60 i. u./mg. In contrast, low molecular weight mucosal fractions had negligible APTT activity, but high (120 i. u./mg) activity by anti-Xa assay. A nominal 1000 units of lung heparin injected I. V. into volunteers gave peak anti-Xa levels of about 0.2 i. u./ml; a comparable injection of mucosal heparin gave peak levels of about 0.3 i. u./ml. The resulting ratio agreed with the anti-Xa activities of these two batches in vitro. However, in vivo, APTT levels with both heparins were less than half the anti-Xa levels, and 50 mins. after injection there was virtually no effect on the APTT, while heparin levels by anti-Xa remained about 0.1 i. u./ml. Although their APTT activities were comparable, lung heparin had much less anti-Xa potentiating effect than mucosal heparin, both in vitro and in vivo; this has important implications for the assay and clinical use of heparin.

scholarly journals Studies with High and Low Molecular Weight Tritium-Labelled Heparin in Vivo and in Vitro

1977 ◽  
Author(s):  
J. N. Shanberge ◽  
S. Ambegaonkar ◽  
T. Kitani ◽  
M. Gruhl ◽  
J. Kambayashi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Anticoagulant Activity ◽  
Lower Molecular Weight ◽  
Low Molecular Weight ◽  
Clotting Time ◽  
Platelet Poor Plasma ◽  
Antithrombin Activity ◽  
Molecular Weight Fractions

When defibrinated platelet-poor plasma 1s chromatographed on Sephadex G-200, fractions with antithrombin-heparin cofactor activity are found 1n only one area. When platelet-poor plasma treated with a tritium-labelled heparin is chromatographed on Sephadex G-200, radioactivity, signifying the presence of heparin, is spread across all of the protein fractions, whereas immediate antithrombin activity is located in two. main areas. Tritiated heparin produced from porcine intestinal mucosa was fractionated on a Sephadex G-200 column with separation of the higher and lower molecular weight fractions. These fractions were added to platelet-poor plasma which was then rechromatographed on Sephadex G-200.With the higher molecular weight, heparin radioactivity appeared in fractions which usually have immediate antithrombin activity, whereas, with the lower molecular weight heparin, it did not. A comparison of the activities of the higher and lower molecular weight material was made after intravenous injection into rats. The higher molecular weight heparin gave higher concentrations of radioactivity in the liver and blood. In addition, the anticoagulant activity as measured by a whole blood recalcification clotting time was maintained for a much longer period. The lower molecular weight heparin was excreted more rapidly in the urine. It is concluded that only the higher molecular weight heparins have anticoagulant activity 1n combining with antithrombin whereas lower molecular weight heparins do not combine with antithrombin but are eliminated in the urine.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

The Effect of Dextran of Various Molecular Weight on the Coagulation in Dogs

1961 ◽  
Vol 06 (01) ◽  
pp. 015-024 ◽  
Author(s):  
Sven Erik Bergentz ◽  
Oddvar Eiken ◽  
Inga Marie Nilsson
Keyword(s):  
Molecular Weight ◽  
Body Weight ◽  
High Molecular Weight ◽  
Bleeding Time ◽  
Factor Vii ◽  
Low Molecular Weight ◽  
Factor V ◽  
Coagulation Mechanism ◽  
Coagulation Defects

Summary1. Infusions of low molecular weight dextran (Mw = 42 000) to dogs in doses of 1—1.5 g per kg body weight did not produce any significant changes in the coagulation mechanism.2. Infusions of high molecular weight dextran (Mw = 1 000 000) to dogs in doses of 1—1.5 g per kg body weight produced severe defects in the coagulation mechanism, namely prolongation of bleeding time and coagulation time, thrombocytopenia, pathological prothrombin consumption, decrease of fibrinogen, prothrombin and factor VII, factor V and AHG.3. Heparin treatment of the dogs was found to prevent the decrease of fibrinogen, prothrombin and factor VII, and factor V otherwise occurring after injection of high molecular weight dextran. Thrombocytopenia was not prevented.4. In in vitro experiments an interaction between fibrinogen and dextran of high and low molecular weight was found to take place in systems comprising pure fibrinogen. No such interaction occurred in the presence of plasma.5. It is concluded that the coagulation defects induced by infusions of high molecular weight dextran are due to intravascular coagulation.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

Applications of Algal Polysaccharides and Derivatives in Therapeutic and Agricultural Fields

2019 ◽  
Vol 25 (11) ◽  
pp. 1187-1199 ◽  
Author(s):  
Soukaina Bouissil ◽  
Guillaume Pierre ◽  
Zainab El Alaoui-Talibi ◽  
Philippe Michaud ◽  
C. El Modafar ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Wound Dressing ◽  
Chemical Processes ◽  
Bioactive Molecules ◽  
Present Review ◽  
Agricultural Fields ◽  
Low Molecular Weight ◽  
Molecular Weight Fractions ◽  
Algal Polysaccharides ◽  
Agricultural Fertilizer

Background: Recently, researchers have given more and more consideration to natural polysaccharides thanks to their huge properties such as stability, biodegradability and biocompatibility for food and therapeutics applications. Methods: a number of enzymatic and chemical processes were performed to generate bioactive molecules, such as low molecular weight fractions and oligosaccharides derivatives from algal polysaccharides. Results: These considerable characteristics allow algal polysaccharides and their derivatives such as low molecular weight polymers and oligosaccharides structures to have great potential to be used in lots of domains, such as pharmaceutics and agriculture etc. Conclusion: The present review describes the mains polysaccharides structures from Algae and focuses on the currents agricultural (fertilizer, bio-elicitor, stimulators, signaling molecules and activators) and pharmaceutical (wound dressing, tissues engineering and drugs delivery) applications by using polysaccharides and/or their oligosaccharides derivatives obtained by chemical, physical and enzymatic processes.

INDUCTIVE AND INHIBITORY ACTIONS OF A LOW MOLECULAR WEIGHT SERUM FACTOR ON IN VITRO MATURATION OF OOCYTES OF THE MEDAKA

1987 ◽  
Vol 8 (5) ◽  
pp. 313-322 ◽  
Author(s):  
TAKASHI IWAMATSU ◽  
SUSUMU Y. TAKAHASHI ◽  
NORIYOSHI SAKAI ◽  
KAORI ASAI
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Serum Factor

Novel concatameric heparin-binding peptides reverse heparin and low-molecular-weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1356-1363 ◽  
Author(s):  
Barbara P. Schick ◽  
David Maslow ◽  
Adrianna Moshinski ◽  
James D. San Antonio
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Tandem Repeats ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
High Affinity ◽  
Binding Peptides

Abstract Patients given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for prophylaxis or treatment of thrombosis sometimes suffer serious bleeding. We showed previously that peptides containing 3 or more tandem repeats of heparin-binding consensus sequences have high affinity for LMWH and neutralize LMWH (enoxaparin) in vivo in rats and in vitro in citrate. We have now modified the (ARKKAAKA)n tandem repeat peptides by cyclization or by inclusion of hydrophobic tails or cysteines to promote multimerization. These peptides exhibit high-affinity binding to LMWH (dissociation constant [Kd], ≈ 50 nM), similar potencies in neutralizing anti–Factor Xa activity of UFH and enoxaparin added to normal plasma in vitro, and efficacy equivalent to or greater than protamine. Peptide (ARKKAAKA)3VLVLVLVL was most effective in all plasmas from enoxaparin-treated patients, and was 4- to 20-fold more effective than protamine. Several other peptide structures were effective in some patients' plasmas. All high-affinity peptides reversed inhibition of thrombin-induced clot formation by UFH. These peptides (1 mg/300 g rat) neutralized 1 U/mL anti–Factor Xa activity of enoxaparin in rats within 1 to 2 minutes. Direct blood pressure and heart rate measurements showed little or no hemodynamic effect. These heparin-binding peptides, singly or in combination, are potential candidates for clinical reversal of UFH and LMWH in humans.

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