scholarly journals On the relationship between the sulphur content and the anticoagulant activity of heparin preparations

1939 ◽  
Vol 33 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Erik Jorpes ◽  
Sune Bergström

1987 ◽  
Author(s):  
G Celia ◽  
M Prosdocimi ◽  
A A Sasahara

Anti-heparin substances, like PF4 or PS, have been studied largely in reference to their ability to neutralize the anticoagulant activity of heparin. On the other hand, few data are available concerning the relationship between GAGs and anti-heparin proteins clearance. We studied the action of PS on human PF4 kinetics in anesthetized rabbits pre-treated with heparin (H, 1000 I.U.), heparan sulphate (HS, 30 mg) and derma tan sulphate (DS, 30 mg). PF4 (given at a dose of 45 μgAg) disappearance reflected its different affinity for the GAGs, with the following half lives (min): control 2.09±0.28, H 14.80±1.47, HS 10.90±1.91, DS 6.87±0.68. Moreover, circulating PF4 (ng/ml) at 1 min was as follows: control 109±8, H 873±134, HS 751±34 and DS 473±15. In another group of H pre-treated rabbits, a bolus injection of PS (10 or 20 mg) caused an immediate disappearance in th.e circulating plasma PF4, from 900±23 ng/ml (1 min after PF4) to 75±11 ng/ml (1 min after 10 mg PS). However, a subsequent H injection 10 min after PS induced a peak release of PF4 (520±21 ng/ml). In a further group of animals pre-treated with HS, the interaction between PS and PF4 was similar to that observed after H treatment. In the last group, pre-treated with DS, the interaction between PF4 and PS was also similar, however, unexpectedly, when 20 mg of PS were given a subsequent bolus of H did not produce any increase of circulating PF4We suggest that PS displaces PF4 from its binding sites on H or HS, thus allowing its uptake by the storage sites in the body, from where it can be harvested again after the subsequent H administration. In the presence of DS again PS is able to displace PF4, however the remaining excess of PS could neutralize the subsequent H injection, thus rendering it unable to induce PF4 release.



Blood ◽  
1948 ◽  
Vol 3 (10) ◽  
pp. 1197-1212 ◽  
Author(s):  
L. B. JAQUES ◽  
ANN G. RICKER

Abstract 1. The relationship between clotting time and heparin dosage has been studied in the dog. 2. On the addition of heparin to blood in vitro, a linear relation is found between heparin dosage and the logarithm of the clotting time obtained. The sensitivity of the blood sample to the action of added heparin is influenced both by the individual (coagulability of the blood before withdrawal) and by the technics of withdrawal and of determination of the clotting time. It is indicated that alterations in the latter may be used to extend the range of measurable hypocoagulability due to heparin. Incubation of heparin with blood for ten minutes increases its anticoagulant effect. 3. When moderate doses of heparin are injected intravenously, five to fifteen minutes are required for the clotting time to reach a maximum. No evidence of a biphasic response was obtained. The maximum clotting time obtained is greater than it is with the same amount of heparin added to the blood in vitro, due to the effect of incubation of heparin with blood on its anticoagulant activity. The in- terval required for the clotting time to return to normal is quite short, and with a given dosage is constant with different animals. Factors influencing the relation between duration of hypocoagulability and dosage are discussed. 4. A test has been devised to determine the sensitivity of the animal to the anticoagulant action of heparin. The clotting time response to certain concentrations of heparin added to the blood in vitro is determined. A fixed dose of heparin is then injected intravenously and the clotting time response is again determined. The response in vitro measures the sensitivity of the clotting system to heparin, while the in vivo response, when interpreted in the light of the in vitro response, measures the ability of the body to remove heparin from the circulation. 5. By means of this test, it has been determined that anesthesia with pentobarbital decreased the coagulability of the blood, urethane had no effect on coagulability, while the effect of ether was variable. The injection of india ink and evisceration caused a hypercoagulability, while removal of the kidneys had little effect. 6. When the sensitivity of the blood to the anticoagulant action of heparin was tested during these procedures, pentobarbital and nephrectomy had no effect, ether caused an increase in sensitivity, urethane a decrease. The injection of india ink and also evisceration markedly decreased the sensitivity of the blood to the anticoagulant action of heparin. 7. Anesthesia with pentobarbital, ether or urethane, the injection of india ink, removal of the kidneys, or removal of the gastrointestinal tract, had no effect on the duration of heparin action in the body.



2007 ◽  
Vol 342-343 ◽  
pp. 721-724
Author(s):  
Byung Won Kang ◽  
T. Yoshida ◽  
Jong Baek Lee ◽  
S.J. Jeon ◽  
H.D. Choi

In order to elucidate the relationship between the structure and biological activity such as anti-HIV and blood anticoagulant activity, sulfonated polysaccharides and amino-polysaccharides having pentofuranosidic structures were synthesized. These sulfonated polysaccharides had potent anti-HIV activity in spite of low molecular weights, and which was dependent on the degree of sulfonation. For the blood anticoagulant activity, the conformation of polymer backbone and sulfamide group plays an important role on the interactions with the blood anticoagulant factor.



2020 ◽  
Vol 120 (09) ◽  
pp. 1270-1281
Author(s):  
Martine Alhenc-Gelas ◽  
Geneviève Plu-Bureau ◽  
Laetitia Mauge ◽  
Sophie Gandrille ◽  
Isabelle Présot ◽  
...  

AbstractInherited protein C (PC) deficiency caused by mutations in the PROC gene is a well-known risk factor for venous thromboembolism. Few studies have investigated the relationship between PROC genotype and plasma or clinical phenotypes. We addressed this issue in a large retrospective cohort of 1,115 heterozygous carriers of 226 PROC pathogenic or likely pathogenic mutations. Mutations were classified in three categories according to their observed or presumed association with type I, type IIa, or type IIb PC deficiency. The study population comprised 876 carriers of type I category mutations, 55 carriers of type IIa category mutations, and 184 carriers of type IIb category mutations. PC anticoagulant activity significantly influenced risk of first venous thrombosis (p trend < 10−4). No influence of mutation category on risk of whole or unprovoked thrombotic events was observed. Both PC anticoagulant activity and genotype significantly influenced risk of venous thrombosis. Effect of detrimental mutations on plasma phenotype was ambiguous in several carriers, whatever the mutation category. Altogether, our findings confirm that diagnosing PC inherited deficiency based on plasma measurement may be difficult but show that diagnosis can be improved by PROC genotyping.



1967 ◽  
Vol 20 (1) ◽  
pp. 153 ◽  
Author(s):  
PJ Reis ◽  
DA Tunks ◽  
OB Williams ◽  
AJ Williams

The sulphur content of wool from 66 Peppin Merino wethers maintained together at pasture was measured in midside staples representing 49 weeks growth. The distribution of sulphur values was normal with a mean of 3�43 % and a range of 3�08-3�92 %. The sulphur content of the wool was inversely related to wool production among these sheep. There were no significant differences in the relationship when wool production was expressed as fleece weight index (F.W.I.), i.e. clean fleece weight/body weight (r = -0�48), as clean fleece weight (r = -0�42), or as wool growth per unit area of skin (r = - 0�37). The mean sulphur content of wool from sheep with the 10 highest values for F.W.I. was 3�27%, compared with a mean of 3 �55% sulphur for wool from sheep with the 10 lowest values for F.W.I.





1977 ◽  
Author(s):  
C. Raby ◽  
H. Bertrand

Thirty five patients with severe evolutive arteriopathy were selected since following the advent of their first accident and although they received classical treatment they experienced at least one or sometimes several relapses of thrombosis. These patients were subjected to discontinuous subcutaneous ambulatory heparin treatment. This treatment consisted of two daily injections of 5,000–10,000 IU calcium-heparin (Calciparine) depending on each patient’s weight, during 30 days every three months. A backward survey of nine years for the patients first treated and of over two years for those most recently examined indicated that such patients never underwent recurrence of the disease and were considerably functionally improved. Experimentally in the animal and after subcutaneous injection of low doses of using 35s labeled heparin we have shown that heparin remains bound both on arterial and venous endothelium at least 15 hours after all anticoagulant activity has disappeared from circulating blood. As a rule and depending on individuals the relationship between the dose and the persistence of heparin bound on the wall is much more constant than that existing between the dose and the duration of the anticoagulant effect. Low doses (100-150 IU/kg in man) repeated twice a day will suffice to ensure the persistence of an endothelial coating. This coating could account for the excellent clinical results obtained.



Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1771-1777 ◽  
Author(s):  
P Sie ◽  
D Dupouy ◽  
C Caranobe ◽  
M Petitou ◽  
B Boneu

Abstract The relationship between the antithrombotic activity of dermatan sulfate (DS) in vivo and its catalytic effect on the inhibition of thrombin by heparin cofactor II (HC II) in vitro was investigated. DS was depolymerized by Smith degradation and the fragments obtained were separated by gel filtration. The fragment of minimal size with full catalytic activity was a hexadecasaccharide, which was further fractionated by affinity for immobilized HC II. Only a small proportion by weight (6.7%) was recovered in the high-affinity fraction, which had about 10 times more catalytic activity than the unfractionated oligosaccharide; the change in activity was primarily caused by the removal of inert materials, recovered in the low-affinity fraction. 1H- NMR spectra indicated strengthening of the signal given by Ido A (2S04) in the high-affinity fraction compared with that of the low-affinity fraction. The anticoagulant activity of the high-affinity fraction was exclusively HC II-dependent. The antithrombotic potency was evaluated in rabbits using the Wessler-thromboplastin model. Half-maximal prevention of thrombosis was obtained after injection of 250 micrograms/kg DS, of 500 micrograms/kg hexadecasaccharide, or of 60 micrograms/kg of its high-affinity fraction. The low-affinity fraction was ineffective at the highest dose tested (1,200 micrograms/kg) and did not potentiate the effect of the high-affinity fraction. These results show that the antithrombotic effect of DS is essentially dependent on HC II binding and activation and that HC II is therefore a suitable target for antithrombotic drugs.



1966 ◽  
Vol 19 (6) ◽  
pp. 1179 ◽  
Author(s):  
LR Piper ◽  
CHS Dolling

The sulphur content of wool may be influenced by a number of factors. Copper deficiency has been shown to reduce sulphur content (Marston 1946), while the administration of sulphur-containing amino acids or casein directly into the abomasum has been shown to increase substantially both the sulphur content of wool and the rate of wool growth (Reis and Schinckel1961, 1963, 1964). Variation in the nutritional status of both pen-fed (Reis 1965) and grazing (Reis and Williams 1965) sheep, associated with variation in either the amount or the composition of the diet, has also been shown to influence sulphur content; wool growth and sulphur content have both increased as nutrition has been improved, and vice versa. Variation in the sulphur content of wool from grazing sheep has also been reported by Ross (1961, 1964) who suggested that there was an inverse relationship between rate of wool growth and its sulphur content. The sheep observed by Ross were Romney ewes and Reis and Williams (1965) have cast some doubt on the relationship suggested by Ross on the grounds that the seasonal variation in wool growth may have been affected by factors other than nutrition.



1968 ◽  
Vol 70 (2) ◽  
pp. 111-116 ◽  
Author(s):  
J. M. Doney ◽  
C. C. Evans

SUMMARYSulphur content, expressed as a percentage of clean dry wool weight, was measured at monthly intervals in two breeds of sheep, Cheviot and Merino x Cheviot backcross (¾ Merino, ¼ Cheviot), offered an equivalent annual amount of feed in three ways—constant level, natural grazing cycle and reversed grazing cycle. The relationships between S content and wool growth rate or nutrient intake differed with both breed and nutrient cycle, but all the results could be explained satisfactorily on the basis of a constant optimum composition for each individual with sulphur impoverishment related to lack of balance between follicle activity rate and high-S substrate availability.The difference in mean maximum S content between breeds (3·87% and 3·81% for Cheviot and ‘Merino’ respectively) was much smaller than the difference between individuals within the breeds (4·05·3·72% and 3·92·3·66%). The seasonal depression within individuals varied with nutrition and wool growth rate, Cheviot sheep showing the greatest depression and lowest values (2·89 and 3·28% for Cheviot and 'Merino, respectively in the reversed cycle group). There was no consistent seasonal trend in the relationship between clean and unscoured wool weight.



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