bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological Activrty and Safety of the Subcutaneous Administration of High Doses of Low Molecular Weight Heparin for 8 Days in Human Volunteers
Authors: Harenberg J , Giese Ch , Dempfle C E , Stehle G , Heene D L 
Published: July 2018

SummaryThis study reports on the biological activity and safety of high dose low molecular weight (LMW) heparin therapy administered by two subcutaneous (s.C.) injections daily for 8 days in healthy human volunteers. Group 1 received 2 × 30 aPTT units LMW heparin/kg bodyweight, and group 2 received 2 × 50 aPTT units/kg per day.In group 1, activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) were uniformly prolonged by 3-5 sec 4 hrs after s.c. administration of heparin. Heptest coagulation time values were prolonged consistently as well by 57 sec on day 1 to 68 sec on day 8. Factor Xa inhibition measured by the S 2222 chromogenic substrate method continuously increased from 0.16 units/ml on day 1 to 0.28 units/ml on day 8.In group 2 prolongation of a aPTT and TCT values increased from 6 sec on day 1 to 15 sec on day 8 and of Heptest time from 70 sec on day 1 to 110 sec on day 8. S 2222 method showed factor Xa inhibitory activity which increased from 0.5 units/ml on day 1 to 0.75 units/ml on day 8. The clinical tolerance of the treatment was good. No changes in clinical chemistry parameters were detected, except for a reversible increase of serum transaminases.The coagulation studies demonstrate accumulation of LMW heparin when high doses are given twice daily. The half life of LMW heparin of factor Xa inhibition increases with increasing doses.Heptest coagulation values were prolonged to 4-6 times the normal values during administration of heparin. S 2222 chromogenic substrate values were in the same range as upon application of high doses of unfractionated heparin. aPTT and thrombin clotting time values ranged from 1.2 to 1.5 times the starting values.
The Inhibitory Effect of GR32191, a Thromboxane Receptor Blocking Drug, on Human Platelet Aggregation, Adhesion and Secretion
Authors: Hornby E J , Foster M R , McCabe P J , Stratton L E 
Published: July 2018

SummaryGR32191, a potent selective thromboxane receptor antagonist, has been shown to inhibit completely prostaglandin endoperoxide and thromboxane A2 (TxA2)-induced platelet aggregation, [14C]-serotonin secretion and β-thromboglobulin secretion. Deposition of human platelets onto damaged rabbit aorta in vitro is reduced in the presence of GR32191 which appears to inhibit aggregation of platelets but not direct adhesion of platelets to subendothelium. The effects of non-prostanoid platelet activating agents whose mode of action requires the biosynthesis of TxA2 are also inhibited by GR32191. Prostanoids which inhibit platelet function, such as prostacyclin or PGD2, retain their inhibitory properties in the presence of GR32191 which does not inhibit phospholipase A2, prostaglandin cyclooxygenase, thromboxane synthase, 12-lipoxygenase or cAMP phosphodiesterase activity. The inhibitory action of GR32191 on platelet aggregation, mural thrombus formation and platelet protein storage granule secretion suggests that it has potential in treatingthrombotic disease in man.
Effect of a Moderate Fish Intake on Haemostatic Parameters in Healthy Males
Authors: Muller A D , Houwelingen A C v , van Dam-Mieras M C E , Bas B M , Hornstra G 
Published: July 2018

SummaryThis article describes the results of a dietary intervention study performed in three different centers. In the study the effect of a diet enriched with fish on the coagulation tendency of blood was investigated. Two groups of 40 volunteers were given a dietary supplement consisting of 135 g of canned mackerel or meat paste (control) for a 6 weeks period.Compliance, monitored by measuring the urinary excretion of lithium, added to the supplements, was about 80%. Before, during and at the end of the experimental period a number of hemostatic parameters, reflecting the coagulation tendency of blood and the procoagulant activity of monocytes, were measured.The fish supplement did not cause a significant effect on the prothrombin time and on the levels of factor VII, activated factor VII, antithrombin III, von Willebrand factor, fibrinogen, plasminogen and a2-antiplasmin. A slight but transient prolongation in the activated partial thromboplastin time was observed as well as a significant increase in the factor X level, which became more pronounced with prolongation of the experimental period; no activated factor X was found.A tendency towards a stimulation of monocyte procoagulant activity was noticed.
The Effect of Lipopolysaccharides (LPS) on Generation of Thromboxane A2 and Thromboplastin Activity in Whole Blood of Males, Females and Females on Oral Contraceptives
Authors: Hansen John-Bjarne , Wilsgård Line , Olsen Jan Ole , Svensson Birgit , Østerud Bjarne 
Published: July 2018

SummaryHeparinized blood sample taken from 81 healthy persons, 40 men and 41 women of whom 17 were on combined oral contraceptives, were incubated with 2 ng lipopolysaccharides (LPS)/ml blood. Quantitation of thromboxane B2 (TxB2) in the resultant plasma revealed a significantly (p <0.001) higher generation of TxB2 in men than in women. No sexual differences were observed in thromboplastin activity in unstimulated and LPS stimulated monocytes. Addition of liposomes together with LPS enhanced the synthesis of thromboplastin 2-10 fold and unveiled a higher synthesis of thromboplastin among men. No differences were observed in TxB2 and thromboplastin synthesis in blood collected from females or females using oral contraceptives. A significant correlation between TxB2 and the thromboplastin activity exists within the male (r = 0.46, p = 0.003) and the oral contraceptive (r = 0.57, p = 0.016) group after exposure to LPS. This study suggests that males exposed to LPS may generate more thromboxane A2 than females and thus be at higher risk of developing thrombosis.The production of thromboxane A2 (TxA2) in platelets upon stimulation may influence the tendency to thrombosis by its proaggregating and vasoconstrictor effect. Although lipopolysaccharides (LPS) lack the ability to induce platelet aggregation in humans (10), Schwartz et al. have reported that mononuclear cells preincubated with LPS induce platelet aggregation most probably through thrombin generation at the surface of monocytes as a result of thromboplastin expression (11).The purpose of this study was to investigate possible differences in the reactivity of whole blood to a weak stimuli of LPS between males, females and females using oral contraceptives.
The Nucleated Thrombocytoid Cells. I. Electron Microscopic Studies on Chicken Blood Cells
Authors: Janzarik H , Morgenstern E 
Published: July 2018

SummaryBy analyses of electron micrographs it was investigated whether nucleated thrombocytes of chickens described in the literature can be differentiated from lymphoid cells with sufficient certainty as an independent cell system. The result was negative. The mixture of lymphoid cells and so-called thrombocytes investigated was extremely polymorphous and, unlike mammalian platelets, proved to be one cell system containing younger and more mature cells. In the literature cells with signs of overmaturity or activation are designated as thrombocytes. Our studies suggest that a genuine thrombocyte system of chickens and other birds is not existent. The cells hitherto considered as nucleated thrombocytes seem to belong to the lymphoid system.
Effect of Glycosaminoglycans on Thrombin- and Atroxin-Induced Fibrin Assembly and Structure
Authors: Carr Marcus E , Powers Patrick L 
Published: July 2018

SummaryThis study was performed to quantitate the impact of several glycosaminoglycans (GAG) on fibrin assembly and structure. Gel formation was monitored as the increase in optical density at 633 nm subsequent to thrombin (2 NIH u/ml) or atroxin (0.10 mg/ml) addition to solutions of buffered fibrinogen (1 mg/ml) or plasma. Gel absorbance was measured as a function of wavelength (400 to 800 nm) and gel fiber diameter and mass/length ratio (μ) were calculated. Chondroitin sulfate A (CSA)shortened the lag phase, enhanced the maximal rate of turbidity increase, and increased the final gel turbidity of fibrin gels formed by thrombin or atroxin. CSA (16 mg/ml) increased fiber μ from 1.3 to 3.1 × 1013 dalton/cm and fiber radius from 6.0 to 8.6 × 10-6 cm in thrombin-induced gels. μ increased from 0.7 to 2.7 × 1013 dalton/cm and fiber radius from 4 to 7.8 × 10-6 cm for atroxin-induced gels. Above 16 mg/ml, CSA caused fibrinogen precipitation in purified solutions but not in plasma. CSA inhibited thrombin-induced plasma clotting of plasma but effects in atroxin-mediated plasma gels paralleled those seen in purified solutions. Chondroitin sulfate B (CSB)-induced changes in fibrin were similar but slightly less dramatic than those seen with CSA. μ increased from 0.9 to 2.0 × 1013 dalton/cm for thrombin-induced fibrin gels and from 0.8 to 2.3 × 1013 dalton/cm for atroxininduced gels. Low molecular weight heparin (Mr = 5100) slowed fibrin assembly and reduced fiber size by 50% in thrombininduced gels. Changes in μ of atroxin-induced gels were much less pronounced (<20%). This study documents pronounced GAGinduced changes in fibrin structure which vary with GAG species and may mediate significant physiologic functions.
Functional Properties of Factor VIIa/Tissue Factor Formed with Purified Tissue Factor and with Tissue Factor Expressed on Cultured Endothelial Cells
Authors: Almus Fanny E , Mohan Rao L Vijaya , Rapaport Samuel I 
Published: July 2018

SummaryFactor VIIa (F. VIIa)/tissue factor (TF) function was examined using purified human TF reconstituted into mixed phospholipid vesicles and TF expressed on cultured human umbilical vein endothelial cells (HUVEC) treated with thrombin. In reaction mixtures containing either type of TF, F. VIIa, 10 nM, either 3H-factor X or 3H-factor IX, 88 nM, and Ca2+, 5 mM, F. VIIa/TF activated factor X (F. X) several fold faster than it activated factor IX (F. IX). Adding heparin, 1 U/ml, increased rates of activation of both substrates and F. X remained the preferred substrate. Adding plasma at concentrations of 5%;or above inhibited factor VIIa/TF catalytic activity. Inhibition was shown to require F. Xa as a cofactor, was prevented by antibodies to extrinsic pathway inhibitor (EPI), and was reversible by decalcification. Thus, with factor VIIa/TF formed with both types of TF, EPI appeared responsible for inhibition induced by plasma. Our data indicate that functional properties of factor VIIa/TF as delineated in reaction mixtures made with purified TF reconstituted into mixed phospholipid vesicles also hold for factor VIIa/TF activity on the surface of cultured HUVEC.
Alpha-2-Macroglobulin Is an Important Progressive Inhibitor of Thrombin in Neonatal and Infant Plasma
Authors: Schmidt Barbara , Mitchell Lesley , Ofosu Frederick A , Andrew Maureen 
Published: July 2018

SummaryAntithrombin III (ATIII) is the main inhibitor of thrombin in adult plasma; α2-macroglobulin (α2M) and heparin cofactor II (HCII) are of lesser importance. The relative contributions of these inhibitors to the inactivation of thrombin may differ during the neonatal period and infancy, when plasma concentrations of α2M are about twice as high as those of ATIII. We therefore compared the relative importance of these anti-proteases for the inhibition of 125I-thrombin in defibrinated pooled adult and neonatal plasma. Observations were also made in pooled plasma of 6 months old infants. 125I-thrombin-inhibitor complexes were quantitated after SDS-PAGE and autoradiography by scanning densitometry. Thrombin (2.5 NIH U/ml) was inhibited more slowly in neonatal than in adult plasma. However, both plasmas inhibited 88% of the added thrombin by 5 minutes. α2M inhibited consistently a larger fraction of thrombin in neonatal than in adult plasma. Consequently, the ratio of thrombin bound to ATIII over thrombin bound to α2M was significantly lower in neonatal (<2.5) than in adult plasma (>4.5; p <0.0001). In infant plasma, this ratio was <2.0. Upon addition of therapeutic amounts of heparin (0.4 U/ml), differences between the contributions of ATIII and α2M to the inhibition of thrombin were no longer apparent, as over 90% of complexed thrombin was bound to ATIII in heparinized plasmas of all age groups. We conclude that α2M is an important progressive inhibitor of thrombin in young infants. This finding may explain why healthy newborns rarely suffer from thrombosis, despite their low plasma ATIII levels.
Plasminogen Interactions with Immobilized Fibrinogen
Authors: Adelman Burt , Ouynn Patricia 
Published: July 2018

SummaryThis report describes the binding of plasminogen to fibrinogen adsorbed onto polystyrene wells. Binding was determined by enzyme linked immunosorbent assay. Both glu- and lys-plasminogen bound to immobilized fibrinogen in a dose-dependent fashion. However, more lys- than glu-plasminogen bound when equal concentrations of either were added to immobilized fibrinogen. Plasminogen binding was inhibited by epsilon aminocaproic acid indicating that binding was mediated via lysine-binding regions of plasminogen. Soluble fibrinogen added in excess of immobilized fibrinogen did not compete for plasminogen binding but fibrinogen fragments produced by plasmin digestion of fibrinogen did. Treatment of immobilized fibrinogen with thrombin caused a small but significant (p <0.01) increase in plasminogen binding. These studies demonstrate that immobilized fibrinogen binds both glu- and lys-plasminogen and that binding is mediated via lysine-binding regions. These interactions may facilitate plasminogen binding to fibrinogen adsorbed on to surfaces and to cells such as platelets which bind fibrinogen.
Elimination of Native and Carbohydrate-Modified Tissue Plasminogen Activator in Rabbits
Authors: Einarsson Monica , Häggroth Lena , Mattsson Christe 
Published: July 2018

SummaryThe elimination of native and carbohydrate-modified tissue type plasminogen activator (t-PA) after an i. v. bolus injection was studied in rabbits. t-PA with a low content of mannose (mant-PA) was obtained by treatment with α-mannosidase, which cleaves terminal mannose from the carbohydrate side chains of the molecule. About 50% of the total mannose was removed from the native t-PA.Clearance of t-PA in rabbits was followed by measurements of both the fibrinolytic activity of the activators and the radioactivity of the iodine-labelled compounds. A biphasic mode of elimination of the fibrinolytic activity as well as of the radioactivity was found with both the native and the carbohydrate modified t-PA. The initial half-life (t½α) was the same, about 1.5 minutes, for both compounds, irrespective of method of analysis. The late half-life (t½β) was also the same, about 15 minutes, for both compounds. However, the β-elimination of native t-PA could only be determined accurately from radioactivity data in the dosages tested, i.e. up to 2 mg of t-PA. No dose dependency in the elimination pattern was observed.In gel filtration experiments, with plasma from the rabbits, it was demonstrated that in addition to fibrinolytically active t-PA and man-t-PA, both fibrinolytically inactive high molecular weight complexes and low molecular weight degradation products of the activators were present in plasma after injection of the compounds.The second phase of elimination .(β) was much more pronounced after mannosidase treatment of the t-PA. The proportion of molecules eliminated with a longer half-life was increased 6-7 times, from about 4% for native t-PA to about 25% for carbohydrate-modified t-PA.Thus, a simple reduction of terminal mannose in the carbohydrate side chains of t-PA does not result in altered half-lives. However, a significantly greater proportion of molecules were eliminated in the late β-phase after the carbohydrate modification. The data also support our recent finding that the mannose receptor on the liver cells is at least in part responsible for the clearance of t-PA.
Eicosapentaenoic Acid Interferes with U46619-Stimulated Formation of Inositol Phosphates in Washed Rabbit Platelets
Authors: Chetty N , Vickers J D , Kinlough-Rathbone R L , Packham M A , Mustard J F 
Published: July 2018

SummaryEicosapentaenoic acid (EPA) inhibits platelet responsiveness to aggregating agents. To investigate the reactions that are affected by EPA, we examined the effect of preincubating aspirintreated rabbit platelets with EPA on stimulation of inositol phosphate formation in response to the TXA2 analogue U46619. Stimulation of platelets with U46619 (0.5 μM) caused aggregation and slight release of dense granule contents; aggregation and release were inhibited by preincubation of the platelets with EPA (50 μM) for 1 h followed by washing to remove unincorporated EPA. Incubation with EPA (50 μM) for 1 h did not cause a detectable increase in the amount of EPA in the platelet phospholipids. When platelets were prelabelled with [3H]inositol stimulation with U46619 of control platelets that had not been incubated with EPA significantly increased the labelling of mos1tol phosphates. The increases in inositol phosphate labelling due to U46619 at 10 and 60 s were partially inhibited by premcubat10n of the platelets with 50 μM EPA. Since the activity of cyclo-oxygenase was blocked with aspirin, inhibition of inositol phosphate labelling in response to U46619 indicates either that there may be inhibition of signal transduction without a detectable change in the amount of EPA in platelet phospholipids, that changes in signal transduction require only minute changes in the fatty acid composition of membrane phospholipids, or that after a 1 h incubation with EPA, activation of phospholipase C is affected by a mechanism that is not directly related to incorporation of EPA.
Purified Human Plasma Kallikrein Does Not Stimulate but Primes Neutrophils for Superoxide Production
Authors: Zimmerli Werner , Huber Isabelle , Bouma Bonno N , Lämmle Bernhard 
Published: July 2018

SummaryIn patients with septicemia and septic shock the contact phase of blood coagulation is activated. It has been suggested that polymorphonuclear leukocytes (PMN) are directly activated by purified plasma kallikrein. This has been recently questioned because granulocytic elastase release induced by recalcification of normal and prekallikrein-deficient plasma was similar. We studied the interaction of different preparations of purified human plasma kallikrein with PMN. Cytosolic calcium shifts were measured with the quin2 method, PMN aggregation was assayed in an aggregometer, and superoxide production was quantitated as superoxide dismutase inhibitable cytochrome c reduction in a continuous assay. No increase of cytosolic free calcium was found during at least 5 min after adding 10 μg/ml plasma kallikrein to PMN. Similarly, highly purified plasma kallikrein from two different sources did not induce PMN aggregation at all, nor did it stimulate superoxide production. However, sequential exposure of PMN to plasma kallikrein and formylpeptide increased the superoxide production compared to stimulation with formylpeptide alone. This phenomenon which is called priming was observed at plasma kallikrein concentrations ≥7 μg/ml. The active site of the molecule was required for the priming, because plasma prekallikrein, active site-inactivated plasma kallikrein, and soybean trypsin inhibitor treated kallikrein did not prime PMN. This indicates that the contact activation system may play a role in host defence against bacterial infection.
A Method for Blood Platelet Homogenization Using the Aminco-French Pressure Cell
Authors: French Paul C. , Holme Randi 
Published: July 2018

SummaryA rapid effective method for platelet homogenization using a pressure cell is described. With this method, almost complete homogenization of human platelets occurred without excessive solubilization of enzymes as compared to a pestle homogenization procedure where there was incomplete homogenization. Electron microscopy of pressure homogenates and fractions revealed well preserved organelles.
Patterns of Incorporation of 75Se-Methionine into Fibrinogen and Other Plasma Proteins in Rabbits Stimulated by Different Test Conditions
Authors: Seligsohn Uri , Rapaport Samuel I. , Zivelin Ariella 
Published: July 2018

SummaryRabbits were injected with 75Se-Methionine (75SeM) 4-8 hr after being subjected to a variety of experimental conditions: injection of ACTH, growth hormone, glucagon, adrenalin, endotoxin, turpentine, hydrocortisone and laparotomy. All of these experimental conditions except injection of glucagon were associated with increased incorporation of 75SeM into fibrinogen. Three patterns of incorporation of 75SeM into plasma proteins were recognized: 1. the pituitary pattern, which was observed in animals injected with ACTH, growth hormone or endotoxin, and which was characterized by increased incorporation of 75SeM only into fibrinogen and by a delayed incorporation of 75SeM into α2 and β1 globulins; 2. the tissue injury pattern, which was characterized by a markedly increased incorporation of 75SeM into fibrinogen and no alteration in incorporation of 75SeM into α2 or β1 globulins; and 3. the pharmacologic corticosteroid pattern, which was characterized by a moderately increased incorporation of 75SeM into fibrinogen and a strikingly increased incorporation of 75SeM into α2 and β1 globulins.
Experimental Study of Rabbit Fibrinogen Degradation Products
Authors: Soria J , Soria C , Vairel E , Prost R. J , Warneson G 
Published: July 2018

SummaryAn experimental study of human and rabbit fibrinogen degradation products, carried out with a parallel assay of plasma plasminogen has allowed us to show that in rabbits the absence, or only slight increase, of serum fibrinogen degradation products during experimental intravascular coagulations was only the consequence of the lower plasminogen level in rabbits than in human beings.
Effects “in Vitro” of Some Cardiovascular Drugs and Other Agents on Human Platelet Aggregation
Authors: Sacchetti G , Bellani D , Montanari C , Gibelli A 
Published: July 2018

SummaryThe in vitro effect of the following substances on human platelet aggregation is studied: K 4423 (a ß-blocking drug), isoproterenol, phentolamine, papaverine, methamidoline (a myolytic agent).None of these substances causes aggregation. All inhibit aggregation induced by ADP or noradrenaline, except for phentolamine, which is active only on noradrenaline- induced aggregation.Hypothesis on the mechanism of action of the compounds tested are proposed.
Insulin and Blood Fibrinolytic Activity
Authors: Hedlin Anne M 
Published: July 2018

SummaryThe effect of insulin on fibrinolysis was studied in hospital patients who were subjected to an insulin tolerance or glucose tolerance test. Blood samples were obtained at frequent intervals over a 2-3 hour period and fibrinolytic activity determined by the dilute whole blood lysis test. Normal control subjects were tested in both fasting and in non-fasting states. A marked increase in fibrinolytic activity was produced during the insulin tolerance test. However, as this increase did not appear until the blood glucose had been reduced to 30-40 mg % it was considered to be due, not to the insulin which had been administered, but rather to the action of those hormones which would be released in response to the hypoglycemia. On the other hand, the results of the glucose tolerance test demonstrated a gradual increase in fibrinolysis during the test period. Again this increased activity could not be attributed to the action of insulin because a similar effect was apparent in the samples obtained from the control subjects. Therefore, it was concluded that the enhancement of fibrinolysis observed in both test and control subjects was not due to the action of insulin.