bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Studies on the Antithrombotic Action of Hirudin in Experimental Animals
Authors: Markwardt F , Hauptmann J , Nowak G , Kleßen Ch , Walsmann P 
Published: July 2018

SummaryThe pharmacodynamics and pharmacokinetics of hirudin were studied in dogs, rabbits and rats. Hirudin proved to be a well tolerated substance with low toxicity. After intravenous injection it was eliminated with a half time of 50 to 60 min. It was nearly completely excreted through the kidneys in biologically active form. The efficacy of hirudin in preventing venous thrombosis, vascular shunt occlusion and disseminated intravascular coagulation in rats was demonstrated.
Lipoprotein Fractions and Antithrombin III Consumption During Clotting
Authors: Winter J H , Bennett B , McTaggart F , Douglas A S 
Published: July 2018

SummaryPlasma and serum antithrombin levels were measured in functional (initial rate measurement) and immunological assays together with serum lipid levels in normal subjects and patients with coronary artery disease. Specific antithrombin activity in plasma showed a negative correlation with triglyceride levels. The consumption of antithrombin activity during blood clotting was negatively correlated with both serum total triglyceride and heparin precipitable lipoprotein and positively correlated with serum high density lipoprotein cholesterol. Different blood lipoprotein fractions may influence the activity of the antithrombin III molecule.
Determination of the Density Distribution of Human Platelets - Methodological Aspects and Comparison with Other Tests for Platelet Activation
Authors: Oost B A van , Hien-Hagg I H van , Veldhuyzen B F E , Timmermans A P M , Sixma J J 
Published: July 2018

SummaryStimulation of human platelets to release results in decreased buoyant density. This decreased density provides a tool to detect circulating platelets which have participated in a thrombotic process. Platelet density gradient centrifugation using Stractan was standardized and the effects of anticoagulation, temperature, and osmolarity were investigated. In 7 out of 32 patients with thrombotic disease less dense platelets were found. Platelet activation in the patient group was also indicated by spontaneous aggregation (10/32), decreased circulating platelet aggregate ratios (5/24) and elevated plasma β-thromboglobulin levels (2/11). Several of these tests were also abnormal in diabetes mellitus thrombocytosis, leukaemia and several systemic diseases with thrombotic complications. The platelet density test using Stractan is reproducible and independent of other tests for platelet activation and is therefore potentially a useful extension of platelet function testing in patients with thrombotic disease.
Alteration in Plasma Proteins and Platelet Functions with Aging and Cigarette Smoking in Healthy Men
Authors: Chao F C , Tullis J L , Alper C A , Glynn R J , Silbert J E 
Published: July 2018

SummaryBlood samples were obtained on four different occasions from 18 cigarette smoking and 34 non-smoking healthy men (age 4Hl9) and analped to assess age- and smoking-associated changes in plasma proteins, btood coagulation and platelet functions. C-ollagen-induced platele t aggregation was signifi cantly inclreased with agng in non-smokers. Significant gfuanges in chronic smokers were increases in platelet count and fibrinogen in plasma; elevation of platelet factor-3 (PF-3) activity in plateletpoor plasma (PPP); increase in serum levels of a1-antitr,?sin, orosomucoid, haptoglobin and properdin factor B; and sfoeftsning of the lag period of collagen-induced platelet aggregation. Filtration of PPP through Mllipore fiIters removed PF-3 membranes. The differen@s in PF-3 activities in fiItered plasma were no longer significant between smokers and non-smokers. Results suggest that chronic smokers have higher levels of acute phase proteins reflecting underlyrng inflammatory processes, and higher levels of PF-3 activity in plasma due to liberation of PF-3 membranes from platelets.
Functional Activities and Concentrations of Plasmin Inhibitors in Normal Subjects and D. I. C. Patients
Authors: Velasco F , Torres A , Andres P , Duran M I 
Published: July 2018

SummaryAlpha-2-macroglobulin and fast antiplasmin, the main inhibitors of the fibrinolytic system, and the presence of plasmin-antiplasmin complex (P-AP) were studied in 15 DIC patients and in 20 healthy individuals. There was a lack of correlation between immunological and chromogenic substrates alpha-2 antiplasmin levels when P-AP complex were found in DIC patients (in 6/15 cases). The levels of alpha-2-macroglobulin were within the normal range in most of these patients, confirm the secondary role of this inhibitor in fibrinolysis.
The Recovery of Platelet Malondialdehyde Production After a Single Intake of Aspirin - The Effect of Dosage
Authors: Takayama Hiroshi , Okuma Minoru , Uchino Haruto 
Published: July 2018

SummaryWe studied the recovery pattern of platelet malondialdehyde (MDA) formation after a single intake of various doses of aspirin (ASA). In normal subjects, there were striking differences in the recovery pattern between large doses (1,000 or 500 mg) and small doses (100 or 50 mg) of oral ASA. The 2 day lag phase was present in the large dose group which showed the complete inhibition of the circulating platelets 2 hr after oral ASA but not in the small dose group which showed the incomplete inhibition. The difference of recovery time between these two groups was about 2 days. These data suggest that ASA’s effect on megakaryocytes might affect the recovery pattern of MDA formation by the circulating platelets. In 2 patients with chronic idiopathic thrombocytopenic purpura, the 2 day lag phase was not observed in the recovery even after a large ASA dose.
“Lupus” Anticoagulant and Thrombosis – Possible Role of Inhibition of Prostacyclin Formation
Authors: Carreras L O , Vermylen J G 
Published: July 2018

SummaryA “lupus” anticoagulant was discovered in 14 patients over a one year period. Only three of them had systemic lupus erythematosus. Bleeding manifestations were only present in one patient with concomitant severe thrombocytopenia. In contrast, eight patients had a history of thrombosis; five of them presented repeated thrombotic episodes. Obstetrical complications (recurrent abortion, fetal death, or intrauterine growth retardation) were observed in six patients. An inhibitory effect of plasma on the production of prostacyclin by vascular tissue was detected in eight patients, six of whom had thrombosis. We suggest that inhibition of prostacyclin formation could play a major role in the pathogenesis of thrombosis and obstetrical problems in some patients with this type of anticoagulant, even in the absence of systemic lupus erythematosus.
Catabolism of Purified Rat Fibrin(ogen) Plasmin Degradation Products in Rats
Authors: Nieuwenhuizen W , Emeis J J , Vermond A 
Published: July 2018

SummaryThe blood clearance of purified plasmin degradation products (X, Y, D-dimer, Dcate, D EGTA, E-fibrin, Ecate and E EGTA) of rat fibrin(ogen) has been studied in a homologous system. Transcapillary flux rate constants, fractional catabolic rate constants and the ratios of intravascular and extravascular pools have been calculated. There are considerable differences in these constants between the two early fibrinogen degradation products X and Y. Also the differences between fibrinogen D and E fragments, derived from different parts of the fibrinogen molecule, are considerable. However, the differences between fibrin fragment D-dimer and fibrinogen fragment Dcate are relatively small. Also the differences between fragments E-fibrin, Ecate and EEGTA are small. The main fraction of all E-fragments is extravascular.
Degranulation of Rabbit Platelets with PAF-Acether: A New Procedure for Unravelling the Mode of Action of Platelet-Activating Substances
Authors: Vargaftig B Boris , Joseph Danielel , Marlas Guy , Chevance L-G 
Published: July 2018

SummaryAggregation and secretion of ATP induced by thrombin, collagen, the snake venom component convulxin and platelet-activating factor (PAF-acether) were studied after the exposure of rabbit platelets to 1 μM of PAF-acether. This concentration, which is around 6 orders of magnitude above the concentration needed to induce full aggregation, was required to remove most of the releasable ATP from the platelets. The depleted platelets aggregated to PAF-acether, to thrombin and to convulxin under conditions where only very low amounts of ATP were secreted, confirming that these agents do not require the release of dense body components to trigger aggregation. Furthermore, when exposure to PAF-acether was associated to inactivation of platelet cyclooxygenase with aspirin, aggregation to thrombin persisted, validating the claim that thrombin induces aggregation by a third pathway unrelated to ADP and to thromboxane A2. Aggregation by collagen was markedly reduced by exposure of the platelets to PAF-acether or to aspirin; when both procedures were associated, aggregation was suppressed. Failure to desensitize the rabbit platelets to PAF-acether upon exposure to high amounts of it indicates the absence of irreversible membrane changes due to PAF-acether, and allows its use as a depleting procedure for the dense body materials, which does not affect platelet membrane components as is the case for thrombin.
On the Reliability of the Use of Heparin Immobilized on Agarose for the Study of the Interactions among Heparin, Thrombin and Antithrombin
Authors: Fish Wayne W , Björk Ingemar 
Published: July 2018

SummaryThe extent of inhibition of thrombin was re-examined as a consequence of the sequence of addition of thrombin and antithrombin III to a column of heparin immobilized on agarose. With the use of pure enzyme, pure inhibitor, and a highly sensitive chromogenic substrate, no appreciable difference in the extent of thrombin inhibition was observed between the two sequences of addition. These observations, together with a demonstrated sensitivity of the method to variations in experimental protocol, challenge the conclusions reached in an earlier work (Hatton and Regoeczi, Thromb. Res. 1977; 10:645) which utilized this experimental approach but which employed larger quantities of reactants and a less sensitive substrate.
Response of Factor VIII/Von Willebrand Factor to Intranasal DDAVP in Healthy Subjects and Mild Haemophiliacs (with Observations in Patients with Combined Deficiency of Factors V and VIII)
Authors: Garcia V Vicente , Silva I Alberca , Borrasca A Lopez 
Published: July 2018

SummaryThe effect of a single standard dose of intranasal DDAVP (260 μg) was investigated in healthy subjects and in patients with mild deficiencies of VIII:C. Changes in FVIII/VWF activities were measured from baseline after 30, 60, 120 and 360 min of administration of the drug. Intranasal DDAVP was followed by a two-fold increase of VIII:C in both groups studied. VIIIR : AG and VIIIR:RCo increased to a lesser extent. Even though FVIII/VWF activities reached their maximum after 60–120 min, a significant increase over baseline was still observed after 360 min. The rise of VIII:C was unrelated to the body weight of the patients and was proportional to the baseline levels of this factor. In two sisters with combined deficiencies of FV/FVIII, the responses in all activities of FVIII/VWF were similar to those seen in mild hemophiliacs. Factor V did not undergo any variation. No alteration in serum osmolarity and no consistent variation in blood pressure or pulse rate were noted. It is concluded that the i.n. administration of a single high dose of DDAVP might be adopted to provide an emergency aid in bleeding patients with mild to moderate haemophilia A and to yield higher VIII:C levels in blood donors.
Bleeding Time in Rats: A Comparison of Different Experimental Conditions
Authors: Dejana Elisabetta , Villa Silvia , de Gaetano Giovanni 
Published: July 2018

SummaryThe tail bleeding time (BT) in rats definitely varies according to the method applied. Of the various variables that may influence BT, we have evaluated the position (horizontal or vertical) of the tail, the environment (air or saline), the temperature (4°, 23° or 37° C) and the type of anaesthesia. Transection of the tail tip cannot be used to screen drugs active on platelet function since it is sensitive to coagulation defects. Template BT in contrast is not modified by heparin and is sensitive to defects of platelet number and function (“storage pool disease”, dipyridamole-like drugs, exogenous prostacyclin). In contrast the test fails to detect aspirin-induced platelet dysfunction. The evidence reported indicates that thromboxane A2-prostacyclin balance is not a factor regulating BT. Aspirin treatment however may be a precipitating factor when associated with other abnormalities of platelet function.Template BT is a valid screening test for platelet disorders and for antiplatelet drugs.
Platelet Hyperaggregability in Ischemic Cerebrovascular Disease and Effects of Aspirin
Authors: Kusunoki M , Kimura K , Nagatsuka K , Isaka Y , Uyama O , Yoneda S , Abe H 
Published: July 2018

SummaryPlatelet aggregation was studied in 24 patients in the chronic stage of ischemic cerebrovascular disease (CVD), with cerebral affluent and effluent blood, i.e., carotid arterial and internal jugular venous blood, and also with peripheral venous blood. Aggregation tests were performed at various final concentrations of sodium arachidonate (A.A.) and ADP. In 17 patients, not taking aspirin, platelet aggregability in jugular venous blood was significantly accentuated compared with that in arterial and peripheral venous blood. This tendency was more marked in the patients with cerebral artery stenosis and/or occlusion than in those with normal cerebral angiogram. In 7 patients taking 500 mg or more oral aspirin, aggregation differences across the brain were not observed and A.A. aggregation and the second phase of ADP aggregation were completely suppressed. These results suggest that a prophylactic administration of aspirin may be beneficial for patients in chronic stage of CVD.
In Vivo Platelet Activation Following Myocardial Infarction and Acute Coronary Ischaemia
Authors: Hughes A , Daunt S , Vass G , Wickes J 
Published: July 2018

SummaryForty-seven patients presenting with acute chest pain had in vivo platelet activity assessed by measuring plasma levels of the platelet-specific protein beta thromboglobulin (BTG), and by screening for the presence of circulating platelet aggregates. Nineteen patients with transmural myocardial infarction (MI), 21 patients with acute coronary ischaemia (CI), and 7 patients with non-cardiac chest pain (NCCP) were investigated in a serial study and compared with a normal control group. The means of all BTG determinations in the MI (34, ± SD = 21-57) and CI (33, ± SD = 19-57) groups were significantly higher than those in the NCCP group (24, ± SD = 17-34; p Ã0.01) and normal subjects (22,5, ± SD = 14-37; p Ã0.001). There was no difference in BTG between those with MI or CI, nor between the NCCP group and normal subjects. Raised numbers of circulating platelet aggregates could not be detected in either MI or CI. The mean BTG levels in both MI and CI patients were significantly raised, compared to normal subjects, on the first day of admission to hospital and remained so on each of the subsequent nine days. Neither heparin plus warfarin nor sulphinpyrazone had any significant effect in lowering BTG levels. 15/40 patients (37.5%) following MI and CI had repeatedly raised BTG levels throughout the study period, and it is suggested that these patients represent an “at risk” group that may benefit from anti-platelet therapy in secondary prevention studies.
Human Plasminogen Variant Chicago III
Authors: Wohl R C , Summaria L , Chediak J , Rosenfeld S , Robbins K C 
Published: July 2018

SummaryA new abnormal, variant, plasminogen Chicago III has been isolated from a patient with recurring deep vein thrombosis. Studies on the plasma fibrinolytic system of four family members showed no inheritance pattern. Kinetics of activation parameters of Chicago III plasminogen with different activators showed lowered catalytic rate constants from 159fold with urokinase, to 3fold with light (B) chain ‧ streptokinase complex, to 1.3fold with streptokinase. The Michaelis constants of activation of Chicago III plasminogen were 16fold higher with streptokinase, 6fold higher with light (B) chain ‧ streptokinase complex, and similar with urokinase. Each of the three activators exhibited different interaction characteristics with this variant zymogen, as they did with variant Chicago I and Chicago II plasminogens (previously reported). However, the latter variants were characterized by having normal catalytic rate constants of activation, with higher than normal apparent Michaelis constants of activation. Chicago III plasminogen, as well as Chicago I and II plasminogens, has a homogeneous population of molecules; the interpretation of the kinetic data was possible only in terms of a single population of molecules. The plasmins derived from Chicago I plasminogen, and also Chicago II and Chicago III plasminogens, have 100% active sites with normal amidase parameters. Basically, a single population of normal isoelectric forms were found in the Chicago III plasma, with three minor forms, about 11% of the total.The kinetic parameters have permitted us to classify the four known plasminogen variants into three different classes. The Class A homozygote (Tochigi) has both an active center defect and a charge mutation difference with normal cleavage of the Arg560-Val peptide bond; the Class B homozygote (Chicago I and Chicago II) has a Km of activation defect with impaired activator binding and normal cleavage of the Arg560-Val peptide bond; and, the Class C homozygote (Chicago III) has both a Km of activation defect with impaired activator binding and a kcat of activation defect, and impaired Arg560-Val peptide bond cleavage.
Effects of Cigarette Smoking on the Ultrastructure of Rat Thoracic Aorta and Its Ability to Produce Prostacyclin
Authors: Pittilo R M , Mackie I J , Rowles P M , Machin S J , Woolf N 
Published: July 2018

SummaryFollowing exposure of rats to graded doses of fresh cigarette smoke, the aortic endothelium examined by scanning electron microscopy regularly showed alterations. These essentially consisted of areas of blebbing and microvillus-like projections from the luminal surface, and the presence in the majority of cases, of micro-thrombi in the low shear areas just proximal to intercostal branches. Aortas from rats exposed to smoke showed a reduction in prostacyclin production in vitro and platelets from these animals aggregated more readily than did those of controls.
Side Effects of Thrombolytic Treatment with Porcine Plasmin and Low Dose Streptokinase
Authors: Marbet G A , Eichlisberger R , Duckert F , Ritz R , da Silva M A , Biland L , Widmer L K , Schmitt H E 
Published: July 2018

SummaryIn the sequential thrombolytic therapy with porcine plasmin and low dose streptokinase side effects are mainly due to bleeding, intolerance reactions are less important. Treatment had to be prematurely stopped in 42 (37%) of 114 DVT cases because of severe bleeding and in 12 (10%) due to intolerance reactions. The corresponding figures for the 45 cases with arterial occlusions are 15 (33%) and 2 (4%) respectively. The intensity of systemic proteolysis as represented by the thromboplastin time is significantly correlated with haemorrhagic manifestations. Macrohaematuria and bleeding from puncture sites are the most frequent haemorrhagic complications followed by spontaneous bleeding into skin and muscles. Non-fatal intracranial bleeding occurred in 1 DVT case (0.9%) and in 2 patients with arterial occlusions (4.4%). The benefit of this potent thrombolytic regimen would greatly improve if a strong reduction of premature treatment stop could be achieved.
Functional Fractionation of Platelets: Aggregation Kinetics and Glycoprotein Labeling of Differing Platelet Populations
Authors: Haver V M , Gear A R L 
Published: July 2018

SummaryPlatelet heterogeneity has been studied with a technique called functional fractionation which employs gentle centrifugation to yield subpopulations (“reactive” and “less-reactive” platelets) after exposure to small doses of aggregating agent. Aggregation kinetics of the different platelet populations were investigated by quenched-flow aggregometry. The large, “reactive” platelets were more sensitive to ADP (Ka = 1.74 μM) than the smaller “less-reactive” platelets (Ka = 4.08 μM). However, their maximal rate of aggregation (Vmax, % of platelets aggregating per sec) of 23.3 was significantly lower than the “less-reactive” platelets (Vmax = 34.7). The “reactive” platelets had a 2.2 fold higher level of cyclic AMP.Platelet glycoproteins were labeled using the neuraminidase-galactose oxidase – [H3]-NaBH4 technique. When platelets were labeled after reversible aggregation, the “reactive” platelets showed a two-fold decrease in labeling efficiency (versus control platelets). However, examination of whole cells or membrane preparations from reversibly aggregated platelets revealed no significant difference in Coomassie or PAS (Schiff) staining.These results suggest that the large, “reactive” platelets are more sensitive to ADP but are not hyperaggregable in a kinetic sense. Reversible aggregation may cause a re-orientation of membrane glycoproteins that is apparently not characterized by a major loss of glycoprotein material.
Diagnosis of Heterozygotes in Glanzmann’s Thrombasthenia
Authors: Stormorken H , Gogstad G O , Solum N O , Pande H 
Published: July 2018

SummaryA study of a family with a propositus suffering from classical thrombasthenia type I has shown that the new immunochemical methods detect heterozygotes with high reliability. There was no overlapping between heterozygotes and normals, and the concentration of the glycoprotein IIb-IIIa-complex is remarkably constant around 50–60% in the heterozygotes. Furthermore, heterozygotes as a group show an increased bleeding tendency.
Esterification of the Carboxyl Groups in Fibrinogen by the Application of a Highly Specific Methylating Agent
Authors: Osbahr A J 
Published: July 2018

SummaryThe trimethyl oxonium ion specifically modified the free carboxyl groups of fibrinogen. This esterification process resulted in the polymerization of the modified fibrinogen molecule with the production of a polymeric material that resembled the physiologically formed fibrin clot. The extent of methylation of fibrinogen was evaluated by methoxyl determination at each step of the polymerization process. The modified fibrinogen polymerized in approximately ten min with a minimum number of methyl groups being incorporated into the fibrinogen molecule. In this manner, it was shown that modification of carboxyl groups in the fibrinogen by a group-specific methylating agent results in polymerization of the fibrinogen.The sites of methylation were ascertained by chromatographic analysis which resulted in the identification of β-methyl aspartic acid and γ-methyl glutamic acid derivatives of the fibrinogen. The analytical methods applied were not able to detect the methylation of any additional amino acid residues in the polymerized-methylated fibrinogen. Based on this experimental data, it was formulated that the methylation of fibrinogen involved the esterification of the carboxyl groups of aspartic and glutamic acid with the resultant reduction of negative repulsion between the fibrinogen molecules and thereby culminated in the polymerization of the modified fibrinogen.