bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect Of Aspirin On The Production Of PGI2 By Various Blood Vessels And Mda By Platelets
Authors: Takada M , Tsukada H , Tanaka H , Gonmori H , Kobayashi N , Maekawa T 
Published: July 2018

This study was desinged to determine whether the differential inhibition of prostacyclin(PGI2) production by vessel wall and malondialdehyde(MDA) production by platelet might be possible by oral administration of aspirin(ASA). Rabbits weghing 2-3kg were used. MDA production by platelet was measured by the Stuart’s method with minor modification. The PGI2 production by vessel wall was assessed by the Moncada’s method with minor modification.The PGI2 production by caval vein, pulmonary artery, pulmonary vein,femoral artery, femoral vein and coronary artery was 148±55%, 136±56%, 153±55%, 134±56%, 123±64%, 103±55% to that of aorta, respectively. The PGI2 production by these vessels was inhibited to 20-40% to their initial level 6h after the single oral administration of 0.3g ASA, and restored to the initial level by 24h, while the MDA production was inhibited more conspicuously and remained at less than 50% of the initial level even 48h.The effect of daily oral administration of ASA on production of PGI2 by aorta and MDA by platelet was investigated. PGI2 production was suppressed to about 10% of the initial level 24h after the last dose of 3 to 7 daily administration of 0,3g of ASA. This indicates that the daily ASA administration results in the cummulative inhibition of PGI2 production. On the other hand, when administered every other day, the same amount of ASA exerted significantly less inhibition of PGI2 production, being at about 50% of initial level 24h after the last dose. MDA production was nearly completely inhibited over the observation periods.These results suggests that the differential inhibition of vascular PGI2 production and platelet aggregation may be possible by the administration of ASA at an appropriate amount and proper interval.
The Effect Of Low Dose Aspirin On Human Venous Prostacyclin Production And Platelet Thromboxane Synthesis
Authors: Hanley S P , Bevan J , Cockbill S , Heptinstall S 
Published: July 2018

This study vas undertaken to determine if there was a dose of oral aspirin that would inhibit platelet cyclooxygenase but that had no effect on venous cyclo-oxygenase. Varicose veins were surgically removed from 68 patients of whom 21 had taken no medicines pre-operatively. Three groups of patients took aspirin 300 mg 14 hours (n=10), 24 hours (n=10) and 48 hours (n=9) pre-operatively. Two other groups took 40.5 mg (n=9) and 81 mg (n=9) 14 hours preoperatively. Two 6 mm discs of venous tissue were incubated with plasma that contained 1 mM sodium arachidonate (NaAA) and the anti-aggregatory activity of the plasma was compared with that of synthetic PGI2 in aspirinised citrated PRP challenged with ADP. PGI2 production in this procedure was confirmed by specific radio-immunoassay for 6-keto PGF1α. All doses of aspirin except 40.5 mg markedly inhibited PGI2 synthesis. Little recovery was seen with 300 mg at 48 hour post-drug.Five normal volunteers took aspirin 300 mg and 5 others 40.5 mg. Citrated PRP was prepared immediately before, 2, 24, 48, 96 and 192 hours after ingesting the drug. The amount of malondialdehyde (MDA, a marker for thromboxane synthesis) that was produced when 1 mM NaAA was added, was markedly reduced compared to the control at 2 and 24 hours by both 40.5 mg and 300 mg and thereafter it returned slowly to control values. This study indicates that 40.5 mg of aspirin inhibits platelet cyclo-oxygenase but not vessel wall cyclo-oxygenase.
Purification Of Vasoactive Peptides From Human Fibrinogen Degraded By Human Leucocyte Elastase
Authors: Wallin R , Belew M , Ohlsson K , Saldeen T 
Published: July 2018

The presence of leucocytes around extravascular fibrin deposits suggests that the leucocyte elastases might be partly responsible for the extravascular degradation of fibrin. Our previous studies have shown that the degradation of fibrin(ogen) by plasmin leads to the release of 2 small peptides which markedly increase vascular permeability and induce oedema e.g. in the lungs. The results of this investigation show that small peptides released from fibrinogen after degradation by leucocytes elastases also increase vascular permeability.Human fibrinogen (Kabi, Grade L) was made plasminogenfree by affinity chromatography on Lysine-Sepharose 4B prior to use. The human leucocyte elastases were isolated from extracts of lysosome-like granules of human leukaemic myeloid cells by a combination of gel filtration, affinity chromatography and preparative agarose gel electrophoresis. The fibrinogen (0.5 %) and the leucocyte elastases (in a molar ratio of 100:1) were incubated together for 48 h at +37°C and at pH 8.5. The mixture was then cooled to +4°C to stop the lysis and ultrafiltrated on a DIAFLO PM 10 membrane until the retentate was approximately 10 % of the starting volume. The peptides in the diffusate accounted for about 20 % of the starting material as estimated from absorbance measurements at 280 nm. The diffusate was concentrated by lyophilization and fractionated by chromatography on a column of Bio-Gel P-6. At least 8 fractions were obtained of which only two showed a significant activity in their ability to increase vascular permeability in rat skin. The active peptides in these two fractions were further purified to homogeneity by column zone electrophoresis at various pHs and their amino acid compositions established.
Some Observations On The Alteration Of The Platelet Membrane Transport Systems In Atherosclerosis
Authors: Ulutin O N , Emekli N , Cizmeci G , Yardimci T U 
Published: July 2018

We have studied the membrane transport systems in the platelets from patients with atherosclerosis with hypercoagulability.No qualitative and quantitative differences were observed in the transport of amino acids in normal platelets or platelets from atherosclerotic individuals. Normally glucose is transported with both an active transport mechanism and diffusion. The active transport of glucose is impaired in the platelets from atherosclerotic patients and this was associated with the loss of a binding protein active in the process. Normal active transport of galactose was unaffected in atherosclerosis. There was an increase, however,in the amount of transported galactose that got incorporated into the platelet glycoproteins in the latter condition. Normal active transport for arachi- donic acid is not observed in platelets from atherosclerotic patients. Indobufen and aspirin did not affect membrane transport of glucose, galactose, and arachidonic acid. Platelet glycoprotein synthesis, however, was inhibited. In addition to the previously reported alteration in the distribution of membrane phospholipids the alterations in the transport functions of the platelet membrane associated with changes in certain carrier proteins provide further evidence for structural modifications of the platelet membranes in atherosclerosis.
The effect of a large dose of aspirin, ticlopidine, and thromboxane A2 synthetase inhibitors on experimental arterial thrombosis
Authors: Kobayashi N , Tsukada H , Takada M , Tanaka H , Gonmori H , Maekawa T 
Published: July 2018

The key role played by platelets in the thrombogenesis has been well recognized. The antithrombotic therapy by inhibition of platelet function has gained considerable support with this recognition. In this report, the effect of a large dose of aspirin,ticlopidine and thromboxane A2 synthetase inhibitors(OKY, AVS) on experimental arterial thrombosis was investigated.The experimental arterial thrombosis was produced by Maekawa’s method. The femoral artery of rabbit was exposed and a steel wire of 0.9 mm in diameter was placed alongside the femoral artery. Then the artery was loosely ligated together with the wire by silk thread. A stricture was made in the femoral artery by pulling out the wire. Ten mg of ellagic acid dissolved in distilled water was injected intravenously. Twenty four hours later, the rabbit again anesthesized and femoral artery with ligature was exposed and examined macroscopically for the presence of occluding thrombosis. In the untreated rabbits, the occluding thrombosis was found in 70 % of the rabbits.In rabbits which ingested 0.3 or 1.0 g of aspirin daily for 7 days, rate of rabbits with thrombus was significantly reduced in spite of marked inhibition of vascular prostacyclin production. Ticlopidine which inhibits the primary aggregation of platelets inhibited significantly the production of the occluding thrombosis. AVS, one of thromboxane A2 synthetase inhibitors, also reduced the incidence of rabbits with the occluding thrombosis. The latter two agents had no inhibitory effect on vascular prostacyclin production.From these results, it is concluded that the formation of our type of arterial thrombosis could be inhibited by the antiplatelet drugs independently of the production of vascular prostacyclin.
Role Of Thromboxane (TXA2 ) And Adp In Collagen-Induced Platelet Aggregation
Authors: Emms H , Lewis G P , Watts I S 
Published: July 2018

TXA2 and prostaglandins (PGs) released during collagen- induced aggregation of rabbit platelets were bioassayed on rabbit aorta (RA) and rat stomach strip (RSS) respectively in a cascade system. Platelet aggregation was monitored simultaneously. The technique was used to examine modulation of aggregation and release of TXA2 and PGs by inhibitors of TX synthetase (l-(7-carboxyheptyl)imidazole) (CHI) and cyclo-oxygenase (CO) (indomethacin, Indo).At low dose collagen (5-10 μg/ml) Indo and CHI completely inhibited platelet aggregation in a dose-related fashion. In contrast, at high dose collagen (50 μg/ml) these compounds gave only a partial (30-40%) inhibition of aggregation, at a dose which abolished CO and TX synthetase activity.The substrate/enzyme combination of creatine phosphate (CP) 5mM and creatine phosphokinase (CPK) 10 units/ml (which converts ADP to ATP) completely inhibited aggregation induced by low dose collagen but only partially inhibited (20%) that induced by high dose collagen. Neither CP nor CPK alone was effective.A mixture of both CP/CPK and CHI abolished the platelet aggregation induced by a high dose of collagen.These studies support the concept that collagen-induced aggregation is dependent on at least two mechanisms.Firstly, at low collagen concentration, subthreshold levels of released ADP and TXA2 act synergistically in inducing platelet aggregation since either CP/CPK or CHI abolished aggregation. Secondly, at high collagen concentration, sufficient ADP and TXA2 are released to induce aggregation independently of each other, since CP/CPK or CHI produced only partial inhibition of aggregation, whilst in combination aggregation was abolished. Furthermore, the results suggest that endoperoxides play no significant role in collagen-induced platelet aggregation.
The Effect Of Ergotamine On The Formation Of Metabolites Of Arachidonic Acid In The Guinea Pig Ear And In Human Platelets
Authors: Vincent J E , Zijlstra F J , Spierings E L G 
Published: July 2018

The relationship between the vasoconstrictor action on one side and a possible effect on the prostaglandin (PG) formation in the vascular system on the other side of ergotamine was investigated. The action of this substance on the formation of thromboxane B2 (TXB2), PGE2, 12L-hydroxy-5,8,10 heptadecatrienoic acid (HHT) and 12L-hydroxy-5,8,10,14- eicosatetraenoic acid (HETE) in platelets was also determined.In both experiments, the formation of the above mentioned substances from {1-14C} arachidonic acid (AA) was measured. The metabolites were separated by TLC.In guinea pig ear slices, a comparatively large formation of PGs occurs. The main substance formed is PGF2α.6-keto F1α, PGE2, PGD2 and PGA2 are also produced. The addition of 10-5M ergotamine leads to an inhibition of the synthesis of all PGs. In the ear, it is likely that the PGs with vasodilator action are dominating. A reduction in PG formation will most probably lead to vasoconstriction.In platelets, the synthesis of TxB2 is inhibited by 5.10-5 M ergotamine. The amounts of PGE2 and HETE are increased. This indicates that the thromboxane A2 synthetase is inhibited.In migraine, platelet aggregation occurs and a partial release reaction. The inhibition of the formation of TxA2 by ergotamine will result in a decrease in this effect. The therapeutic action of this substance may be related, at least in part to the changes induced in the transformations of AA in both systems.
Effect Of Heparin And Protamine On The Antithrombin Activity Of α2-Macroglobulin
Authors: Shanberge J N , Love J , Swanborg N 
Published: July 2018

It has been shown that certain fractions of porcine mucosal heparin may form complexes with α2-macroglobulin but still retain their capacity to activate antithrombin III. These heparin fractions are not neutralized by protamine. The effect of heparin and protamine on the antithrombin activity of α2-macroglobulin has now been studied.Plasma to which a tritium-labelied heparin was added was chromatographed on Sephadex G-200. The macromolecular fractions, in which there is heparin (indicated by radioactivity) and α2-macroglobulin (demonstrated by radial immunodiffusion), have no immediate inhibitory action on the thrombin clotting time (TCT) of fibrinogen but do inhibit the TCT of whole plasma. In addition, these fractions have progressive antithrombin activity (PATA) but less than that in fractions containing α2-macroglobulin obtained with non-heparinized plasma. Fischer et al stated that heparin complexes with thrombin to prevent its inactivation by α2-macroglobulin. However, when the heparinized plasma is “neutralized” with protamine sulfate prior to chromatography, the PATA of the macromolecular fractions is reduced further even through these fractions still have immediate inhibitory action on the TCT of plasma. When the same concentration of protamine is added to non-heparinized plasma, the PATA in the macromolecular fractions is not altered. Treatment of the macromolecular fractions from heparinized plasma with triethylaminoethyl cellulose removes the immediate inhibitory action on the TCT of plasma but does not affect the PATA of the fractions. How the heparin and protamine interact to decrease the PATA of α2-macroglobulin containing fractions is not as yet determined. Recently it was found that a similar complexing of heparin fractions with α1-antitrypsin may occur in the same way as with α2-macroglobulin.
Studies On The Interaction Between Factor Va And Factor Xa
Authors: Lindhout M , Govers-Riemslag J , Rosing J , Hemker H 
Published: July 2018

Thrombin activated bovine factor V is composed of two polypeptide chains with molecular weights 94,000 and 80,000. The two polypeptide chains are complexed via Ca2+ions.Factor Va enhances the rate of thrombin formation by drastically increasing the Vmax of the prothrombin activation. We have undertaken a study of the interactions of factor Va with the different components of the prothrombinase complex (e.g. factor Xa and prothrombin), in order to get more insight in the mode of action of factor Va.Our kinetic experiments in solution show that the functional enzyme in the prothrombinase complex is a equimolar complex of factor Va and factor Xa. The dissociationconstant, as determined over a wide range of prothrombin concentrations, has a value of 3×10-9M.For the stimulating effect of factor Va on the prothrombin activation by factor Xa in solution, the presence of Ca2+ions is required. The dissociationconstant of the Va-Xa complex was found to be independent of the Ca2+ concentration. In order to reveal whether an interaction between Ca2+ and γ- carboxyglutamic acid residues is responsible for the observed Ca2+ requirement, identical experiments were carried out with decarboxyfactor Xa and decarboxyprothrombin. The isolated polypeptide chains of factor Va have, in the presence or absence of factor Va, no effect on the kinetic parameters of the prothrombin activation. This let us conclude that there is no interaction between factor Xa and the separate polypeptide chains of factor Va.The affinity of factor Xa for negatively charged phospholipid or stimulated bloodplatelets is greatly enhanced by the presence of factor Va. Our Kd value measured for the Xa-Va complex in combination with reported dissociationconstants of factor Xa-phospholipid and Factor Va-phospholipid complexes give a quantitative explanation for the above mentioned effect of factor Va on the binding of factor Xa to phospholipid membranes.
The Evaluation Of Platelet Suppressing Drugs In Patients With Unstable Angina
Authors: Gent M , Cairns J , Sackett D , Singer J 
Published: July 2018

A double-blind, randomized multi-hospital study is in progress to investigate, among patients with unstable angina, the efficacy of aspirin (1300 mg daily) and sulfinpyrazone (800 mg daily), both singly and in combination, in reducing mortality, both overall and cause-specific; myocardial infarction; recurrence of unstable angina; and the frequency of aorto-coronary bypass surgery. It is proposed to enroll approximately 600 patients from six coronary care units and to follow each patient for up to two years.An outline of the study design and execution will be presented and some of the specific methodological problems associated with this study will be discussed. In particular, attention will be drawn to the difficulty of recruiting patients to this type of trial (8000 patients screened to produce the first 200 patients actually entered into the study) and to the confounding created by other interventions among these patients, including both medication and coronary bypass surgery. An interim assessment of efficacy will not be presented but some overall descriptive data relating to patient characteristics, protocol adherance, and outcome measures will be summarized.
Intermittent Calf Compression: A Randomized Trial In Elective Hip Replacement
Authors: Gallus A , Darby T 
Published: July 2018

We have evaluated venous thrombosis prevention with intermittent calf compression in 78 patients aged over 50 years having elective hip replacement. 38 patients were randomly allotted to intermittent calf compression with a “BOC-Roberts Venous Flow Stimulator”, begun at the start of surgery and continued for 7 days, while 40 patients had no prophylaxis. Age, weight, length of surgery, and other risk factors were similar in the two groups. All patients had ascending venography of the operated leg on the seventh day, or bilateral venography if routine 125I fibrinogen legscanning and impedance plethysmography suggested thrombosis on the unoperated side.Venography showed thrombosis in 12/38 patients treated with intermittent calf compression (32%) and 21/40 untreated patients (53%). The difference is not statistically significant, but further analysis showed some interesting treatment effects: (a) calf vein thrombosis was found in 13% of treated and 35% of untreated patients (p <0.05), (b) femoral or popliteal vein thrombosis developed in 24% of treated and 38% of untreated patients, while isolated femoral vein thrombosis (without calf vein thrombosis) developed in 18% of treated and untreated patients, but (c) the femoral vein thrombi were smaller in treated patients - 8% of treated and 30% of untreated patients had femoral vein thrombi with an estimated length above 5 cm (p <0.05).This suggests that intermittent calf compression prevents calf vein thrombosis and prevents extension of femoral vein thrombi after elective hip replacement, although it cannot prevent the initiation of femoral vein thrombi which is presumably due largely to local vein trauma. This limited effect may be clinically valuable, allowing delay in starting anticoagulant prophylaxis until this is safe.
Variable Results With Plasma Exchange In Thrombotic Thrombocytopenic Purpura
Authors: Simon Toby L 
Published: July 2018

The clinical efficacy of plasma exchange with fresh frozen single donor plasma in thrombotic thrombocytopenic purpura (TTP) was evaluated. Six patients with the classical findings of TTP, had plasmapheresis using the Haemonetics Model 30. Treatments were initiated daily. Two to three liters total exchanges were done; 1-1½ liters fresh frozen plasma were infused with each exchange. In five of the six cases, therapy was begun immediately after diagnosis. Steroids and antiplatelet agents were also used. Five of the patients were comatose when treatment was begun; the sixth had neurological symptoms of memory loss and aphasia with severe hemolytic anemia and thrombocytopenia. Circulating immune complex measurements were performed in all patients prior to treatment using the Clq and Raji cell assays.Three patients (2 in coma) responded to therapy. The two comatose patients required more than four daily treatments before beginning to respond (followed by four and six alternate day treatments, respectively). The third patient went into remission after four daily treatments. Three patients in coma died, two deteriorating after the first plasma exchange. The third, treated after a delay due to severe cardiac complications, subsequently died.The three responding patients were younger than the three who died. The two in coma who responded to therapy had a longer course of symptoms (suggesting disease onset prior to onset of coma) than the three who died. Circulating immune complexes by the Clq assay were negative in all six patients. The Raji cell assay was positive in one patient.Even severely ill comatose patients with TTP respond to plasma exchange, but aggressive, persistent therapy may be required before response is seen. More fulminant disease with rapid onset may fail to respond. Circulating immune complexes do not appear to mediate the disease process.
Interaction Of Tritiated-Quinine With Human Platelets In The Presence Of A Quinine-Dependent Antibody
Authors: Christie D J , Aster R H 
Published: July 2018

In drug-induced immune thrombocytopenia, it has not been established with certainty whether drug binds first to the platelet membrane or to antibody to promote platelet-antibody binding. The association of the drug, quinine, and a quinine dependent antibody (obtained from a patient with drug-induced thrombocytopenia) with human platelets was studied using a tritiated derivative of quinine prepared by catalytic hydrogen exchange. Tritiated quinine binding to platelets was measured in the presence of the antibody or normal human serum (NHS). Platelets were stirred with the appropriate reagents at room temperature for 20 minutes and washed. Bound tritiated quinine was measured by scintillation techniques.Two types of drug binding sites, antibody-dependent and antibody-independent, were demonstrated on platelets. In the presence of NHS, fewer than 20,000 molecules of drug became tightly bound to the membrane. In the presence of excess antibody, approximately 200,000 molecules of quinine became membrane-bound. Antibody did not bind to platelets in the absence of drug. These findings appear to provide the first demonstration of antibody-dependent binding of quinine to platelets and suggest that interaction of drug and antibody in the soluble phase precedes the binding of either constituent to the platelets (“innocent bystander mechanism”). The use of radioactive drugs appears to provide a useful tool for the investigation of the molecular basis of drug- induced immune disorders.