bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Inhibitory Effect Of Dilazep On Adhesion And Aggregation Of Platelet Following Aortic Intimal Injury In Rabbit
Authors: Sumiyoshi A , Hayashi T , Fujii M 
Published: July 2018

The inhibitory effect of dilazep and aspirin on in vivo platelet adhesion and aggregation in rabbit aorta subjected to endothelial injury was investigated. Endothelial injury was induced by insertion of polyethylene tubing from the femoral artery into the aorta. In the beginning before surgery, experimental animals were intravenously given sufficient drug to inhibit platelet aggregation in vitro in response to ADP and collagen. For a quantitative analysis of platelet accumulation on the damaged aortas, 51Cr-labeled platelets were used. For morphological study, the aortas were fixed by perfusion at one hour after injury and examined by light and scanning electron microscopy for platelet adhesion and aggregation in injured area.Radioactivity of damaged aortas in rabbits administered dilazep (50 or 100 μg/kg) or aspirin (10 mg/kg) was significantly lower than in rabbits untreated by drug. Dilazep and aspirin did not prevent completely the adherence of platelets on injured area of the aorta, but inhibited considerably the platelet aggregation to form raised platelet thrombus.
Clinical Evaluation Of Wave Conformation Of Photo- Pletismograph And Doppler In Distal Angiopathies
Authors: Pavlovsky M , Meschengieser S 
Published: July 2018

Objective studies and interpretation of circulatory problems in hands and feet are difficult. Several non invasive techniques for vascular diseases developed in recent years may have great application in small vessels.We have studied 280 patients with distal circulatory problems;recording(graph)the flow patterns obtained in a) distal arteries of the arm and leg with a bidirectional Doppler of 9.4 MH,and b) the skin arterioles at the tips of fingers and toes with a photopletismograph EP 100 (PP). The general patterns obtained comparing the waves at the graph recorded with the PP and Doppler were: A) a similar shape wave;B) a slight atenuation of the PP waves;C) a decrease of PP waves;D) an increase in PP waves. Patterns A and B are consider ed normal;Patterns C-D are abnormal.In vasospastic disorders great modifications of PP waves could be observed,with changes from patterns C to D or viceversa with the effect of stress-temperature and drugs. Degenerative arterio-pathies of big and small vessel could be distinguished evaluating the relation of the waves of both systems. Measurements of distal segmental pressures and the recovery time of pulse in fingers of toes with both systems add valuable information. We observed differences in wave types in some individuals, between Doppler and PP which are difficult to explain with our actual knowledge.We have found that the combination of both methods is an excellent objective system for the better study and drug therapy control of different small vessel diseases.
Experimental Thrombogenesis By A Non-Invasive, Non-Traumatic Method
Authors: Hamer J D , Malone P C , Sevitt S 
Published: July 2018

A method is described for producing thrombi in the femoral veins of dogs by non-invasive, non-traumatic means.Previous studies have shown a decline in venous PO2 in the depths of valve pockets during non-pulsatile flow, which may be reflected in progressive endothelial hypoxic injury. It has also been shown that healthy well oxygenated platelets and leucocytes attach themselves to such damaged endothelium.Dogs anaesthetised by Sagatal (Nembutal) were kept in the supine position with extended legs for 6 hours; some were not allowed to move or be moved for the whole experimental period; others had their legs moved passively at 20 minute intervals - these two groups were “motionless” and “frequently moved” controls. The third (experimental) group were kept motionless for 2½ hours, and allowed to wake slightly as the first anaesthetic dose wore off; during this time they began to shiver. This movement effects pulsatile venous flow and vibrates the valve cusps in the deep vein. Venography was employed to identify the presence of thrombi which were checked at autopsy.Results showed numerous (70%) “classical”.thrombi among 12 limbs in the experimental group. Of the 18 control limbs only one showed a thrombus, this being in the frequently moved group. No thrombi were found in the 10 limbs left motionless.The hypothesis that endothelial hypoxia is the primary instigator of deep venous thrombosis, therefore appears to be supported. Thrombosis develops when pulsatile flow is restored. The animal model described is the subject of developmental studies, and is available for further investigation of interaction between blood elements and venous endothelium, together with prophylactic techniques.
Role Of Prothrombin And Factor IX In The Initiation Of Thrombus Formation
Authors: Kennedy F , Hassouna H I , Penner J A , Schultz J 
Published: July 2018

This study was designed to investigate the role of plasma clotting factors in the initiation of thrombus formation on materials intended for prolonged blood contact. Prothrombin was isolated from dog plasma using BaC03 adsorption, citrate elution and chromatography on dextran sulfate. Antibodies against various fractions were purified and tested for their ability to inhibit clot formation in normal dog plasma. Prothrombin time was not significantly affected by antibodies, but recalcification time was more than doubled. This recalcification time was not corrected by adding BaC03 adsorbed plasma back to normal dog plasma incubated with antibody. These results led to the conclusion that these antibodies were specifically inhibiting prothrombin and factor IX.These purified antibodies were tested in preconditioned male dogs to specifically block prothrombin from taking part in coagulation. Dogs had previously been surgically fitted with arteriovenous shunts between the carotid artery and the internal jugular vein, and were given autologous platelets labelled with Cr and 125I-labelled human fibrinogen prior to testing. The arteriovenous shunt was opened into the flow chamber for one hour, during which time a dual channel scintillation counter was positioned over the test chamber to monitor fibrinogen and platelet deposition at 5 minute intervals. After one hour the chamber was removed and the size of the resulting thrombus was measured by total weight, fibrinogen, red cell, and platelet content. In dogs previously given antibodies against prothrombin, thrombus was not found on the various biomaterials applied to the rod within the flow chamber. We conclude that prothrombin is of major importance in the initiation of clot formation on artificial surfaces.
Phospholipid Topography Coagulation
Authors: Hemker H C , Zwaal R F A , Rosing J , van Dieyen G , Bevers E 
Published: July 2018

Phospholipids play a role in thrombin generation because the constitute the support on which both the factor X activating enzyme (“tenase”) and the prothrombin activating enzyme (proth rcmbinase) are built.In model systems with pure synthetic phospholipids it can be shown that the binding of the coagulation factors to a phospholipid surface is a function of both phospholipid charge and membrane fluidity. A relatively high molefraction of phosphatidyl serine (PS) is a prerequisite for optimal binding of the vitamin K dependant factors. Precise measurements on the binding constant and the number of binding sites of factor X show that at molefractions of PS between 0.01 and 0.25 aproximately one PS binds per Gla-residue. Above 0.25% of PS vesicle agregation occurs.The normal intact circulating platelet shows a molefraction of PS of ̴ 0.03 in the outer leaf let of its plasma membrane and therefore hardly if at all stimulates thrombinformation.Upon activation by thrombin (2nM) together with collagen, (10μg/ml) the outer leaflet aquires increasing amounts of PS without platelet disruption taking place.This suggests a flip-flop movement of phospholipids across the membrane as part of the activation reaction of platelets. It can be shown that optimal “tenase” supporting phospholipid compositions appear before prothrombine supporting ones. The activation by thrombin and collagen is only partly inhibited by prostacyclin even at high concentrations.
New Developments In Interactions Of Blood With Artificial Surfaces
Authors: Salzman E W 
Published: July 2018

There are major new developments concerning interactions of blood with artificial surfaces. There is new understanding of mechanisms: the nature of the plasma protein film adsorbed on artificial surfaces, the interaction of HMW kininogen with adsorbed fibrinogen, the significance of adsorbed antithrombin to the behavior of heparinized surfaces, and the lack of prostacyclin production and ADPase activity. There are new in vivo diagnostic methods: measurement of labelled platelet and fibrinogen survival, assay of plasma levels of products of activated coagulation or platelets (FPA, thrombin/antithrombin complexes, β - thromboglobulin, platelet factor 4 thromboxane B2), and in vivo detection of thrombi with 125I-fibrinogen or 1 Inplatelets. New methods also exist for characterization of surfaces: ESCA, SEM, TIRIS, TIRFS. New materials are available with different modes of thromboresistance: bland polymers such as polyurethanes and siloxanes, modified collagens, heparinized surfaces, porous materials, and aldehyde treated materials of animal origin. There are new drugs for protection of hemostatic elements during extracorporeal circulation: PGI2, PGE1, ibuprofen. New applications for prosthetic devices have become practical: peritoneo-jugular shunts for treatment of ascites, left ventricular assist devices, intra-aortic balloon pumps, total artificial hearts.Such developments raise important new questions: the relation of short-term tests of thromboresistance to longterm behavior of devices in vivo, the problem of thrombi at the junction of prosthetic device with the host, calcification in long-term applications, and new approaches to management of traditional clinical problems (e.g., continuous treatment with portable miniaturized hemodialysers, small vessel prostheses, extracorporeal cardiopulmonary support without anticoagulation).Subsequent speakers will consider these topics more fully.
Relationship Between Factor VIIIR:Ag, Factor VIII C And Glycoemic Control And Vascular Complications In Insulin-Dependent Diabetics
Authors: Tantalo V , Rossi E , Cossu M M , Migliavacca P , Saibene V 
Published: July 2018

Increased levels of Factor VIII are usually re ported in diabets mellitus, even if contradictory relationships with the vascular complications have been observed,due to unselection of patients. We have measu red Factor VIIIR:Ag and Factor VIII C(two stages method) in 60 insulin dependent diabetics (IDD), aged between 7 and 78, compared to 25 sex and age matched normal controls (NC).The presence of retinopathy (r) or macroangiopathy (m) was assessed by fIuoroangiography and EKG plus oscillography, respectively.No significant correlations were found between FVIIIR:Ag, FVIIIC and concomitant blood glucose, glycosylated hemoglobin, GH, and the duration of diabetes. A progressive increase in FVIIIR:Ag according to the extent of the vascular damage is evident. An enhancement of the level of FVIIIC, greater than that of FV IIIR:Ag, index of enhanced thrombin production, is already present even in absence of vascular damage in IDD, being more pronounced in patients with vascuIar complications.
The Use Of Factor VIII:C Depleted Normal Plasiia In The Factor VIII:C Assay
Authors: Pancham N , Bogdanoff D , Mintz C , Wada S , Coan M 
Published: July 2018

Normal plasma was made deficient in functionally active FVIII:C. This plasma supplemented with bovine FV was used as a substrate and compared to hemophilic plasma in the FVIII:C assays. The assays were performed on mechanical as well as optical clot detecting systems using the one-stage procedure.Using a statistically valid experimental design, the plasma artificially-deficient in FVIII:C was shown to be comparable to hemophilic plasma, when both FVIII concentrates and pooled normal plasma samples were assayed. The plasma artificially deficient in FVIII:C was stable upon freezing and thawing and upon reconstitution after freezedrying. Batch-to-batch variation was not significant. The introduction of this plasma as a reagent eliminates the need for collecting hemophilic plasma which may contain inhibitors to FVIII.The main conclusions of the analyses are that artificially deficient FVIII substrate is fully comparable to naturally deficient human substrate in both accuracy and precision.
Heated Lyophilized Factor VIII And Factor IX Concentrate Preliminary In Vitro Studies
Authors: Rubinstein A 
Published: July 2018

It has been known that albumin and plasma protein fraction (PPF) do not transmit hepatitis since these products are heated at 60°C for 10 hours. This heating is sufficient for inactivation of hepatitis virus. It has been previously tried to heat the Cohn Fractions leading to Factor VIII and Factor IX Concentrates in solution, however, this has resulted in significant loss of Factors VIII and IX.We have taken lyophilized Factor VIII Concentrate powder and heated it in a waterbath at 60°C for 10 hours and have demonstrated no significant change in in vitro recovery of Factor VIII activity four hours following the heating. The same was shown for recovery of Factor IX activity after heating lyophilized Factor IX concentrate for 10 hours at 60°C. In addition Factor IX activity was not destroyed following heating of the lyophilized powder for 20-30 minutes at 100°C. This is significant because now potentially this heated lyophilized powder of Factor VIII and Factor IX is free of previous risk of transmission of hepatitis. However, the effect of heating on the thrombogenic effects in vivo of the concentrates and complications was not assessed in this study. Chimpanzee studies are planned to determine whether the heating has inactivated the hepatitis virus.It is possible that a longer heating time will be needed to sufficiently inactivate the hepatitis virus in the lyophilized state.
Use Of Chromogenic Peptide Substrate Assays In The Evaluation Of Surgical Treatment Of Intraabdominal Sepsis
Authors: Smith-Erichsen N , Aasen A O , Amundsen E 
Published: July 2018

Chromogenic peptide substrate assays were included in the evaluation program of 14 patients having surgical treatment for intraabdominal sepsis.Six of the patients survived, whereas eight died. The six survivors had a total of 19 operations (1-5 operations /patient). The eight fatal cases had a total of 14 operations (1-2 operations/patient). Plasma prekallikrein (PKK), functional antikallikrein (KKI), plasminogen (Pig), fast antiplasmin (AP) and functional antithrombin III (AT- III) values were determined using chromogenic peptide substrate assays. Hageman factor levels (HF) were determined using a coagulation assay with a HF deficient plasma. α2-Antiplasmin (α2AP), CI-esterase inhibitor (CIINH), α2- Macroglobulin (α2M) and AT III were determined immunochemically.In both the fatal cases and the survivors PKK, HF, Plg and AT III values were found markedly reduced during sepsis. The reductions of PKK and AT III were significantly more pronounced in the fatal cases than in the survivors. During sepsis the ratio of functional activity versus immunochemical values decreased when compared with normals for α2AP, CIINH and AT III. Whereas the parameters remained reduced in the fatal cases, gradual increases towards normal values for PKK, HF, Plg and AT III were found within two weeks in the survivors. Clinically and by autopsy all the fatal cases were evaluated to have a persistant intraabdominal septic focus.It is concluded that chromogenic peptide substrate assays appear to be of great value in evaluating surgical treatment of intraabdominal sepsis.
Studies On The Various Causal Factors Related To Hypercoagulability In The Field Of Obstetrics. With Special Reference To The Onset Of Dic As Viewed From The Changing Of Kinin-Kallikrein System And Fibrinopeptide A
Authors: Suzuki S , Murakoshi T 
Published: July 2018

Purpose: In order to follow the changes accompanying the develop of the foetus and placenta which has the activation of thromboplastin in its background, in addition to the studies on hypercoagulability done hitherto, the changing of the Kinin-Kallikrein system were investigated. This changing of the Kinin-Kallikrein system is controlled by Hageman factor which is considered to be the source of coagulation. The change of Kinin-Kallikrein system was investigated along the gestational monthes. On the other hand, from fibrinogen and its metabolized products which are considered to be the precursor of FDP and which is involved in the 3rd stage of coagulation especially from increasing and decreasing of Fibrinopeptide A(FPA) and the Soluble Fibrin Monomer Complex (SFMC) the hypercoagulability was analysed, and prediction of DIC was attempted.Method: 70 cases of pregnancies (30 cases of delivery, 12 cases of premature separation of the placenta, 13 cases of abortion, 15 cases of EPH-Gestosis.) were examined and i) Kininogen(by Bioassay and Radioimmunoassay) and prekallikrein(S-2302) which are the control-substances of the KininKallikrein system were measured, ii) Fibrinopeptide A was measured by Radioimmunoassay and SFMC was measured with Agarose Gelfiltration.Results: i) As in the case of the majority of the coagulation factors, Kininogen, and Prekallikrein showed a definite increase during pregnancies, and it was noted that at the end of pregnancies prekallikrein showed values of 190.0±31.6 %(normal values 90-110%) and at the onset of labour pains the values showed a lowering to (76.5±12.6%) and especially it was noted that in the DIC group the values were remarkably low(38.6 ±8.8%). ii) Both Fibrinopeptide A and SFMC showed a remarkable increase (14.0±5.1 ng/ml-FPA, normal value under 2 ng/ml) and in DIC cases a still further remarkable increase of 26.0±6.8 ng/ml was seen.
Study Of The Ratio Expression For Prothrombin Time And Activated Partial Thromboplastin Time Results
Authors: Leclercq R 
Published: July 2018

Prothrombin time (PT) and activated partial thromboplastin time (APTT) results are statistically different, not only in function of reagent used but also, with a same reagent, in function of the degree of automation of the measuring device. It has been claimed that using time ratio of pathological to normal samples would reduce these discrepancies.In a national voluntary quality control program using Verify Citrate Normal and Pathological I/II plasmas, pairs of results obtained in the same analytical batch were computed to compare mean values and reproducibility of ratios and seconds for both PT (n=1764) and APTT (n=1392). Results were screened simultaneously for origin of reagent and measuring technique.Concerning PT, the ratio expression did not improve the intralaboratory dispersion of results for both pathologies levels. Neither in group comparisons between couples reagent-device, nor for the whole set of pooled values, a significant improvement of the dispersion of the ratio results could be observed if compared to the dispersion expressed in seconds. In the 6 groups reagent-instrument, difference between average values was never greater than 1.0 sec for the Normal control plasma (mean: 11.7 sec), 2.4 sec for the level 1 plasma (mean: .18.9 sec) and 4.9 sec for plasma level 2 (mean: 29.3 sec).Concerning APTT, dispersion was strongly enhanced in semi-automated equipments. Chemical activators gave times longer than the particulate ones. Here again, no significant improvement was offered by the ratios.In conclusion, ratio expression of PT’s and APTT’s results does not abolish the influence of the couples ‘origin of reagent’ - ‘automation of measuring device’.
Thrombin Generation Stimulated By Oxidation Products Of Linolenic And Arachidonic Acids
Authors: Barrowcliffe T W , Gray E , Gutteridge J M C , Kerry P J 
Published: July 2018

Autoxidation of unsaturated fatty acids yields mixtures of products which have potent biological activities in several systems. Such products have been shown to cause platelet aggregation and to stimulate thrombin generation in platelet-free plasma. The thrombin generating activity of products obtained by air or 02 oxidation of linolenic and arachidonic acids was studied by standard in vitro clotting methods. Products were separated from the starting material by a variety of techniques, the most successful being column chromatography on phenoxymethyl lipidex, a modified LH- Sephadex.Clotting studies showed that thrombin generating activity proceeded via the intrinsic system, requiring Factors VIII, IX and X but not Factor XI. Studies with lipoprotein-free plasma indicated that part of the activity of the oxidation product was a ‘surfactant’ effect, involving release of coagulant-active phopholipid from plasma lipoproteins. Such an effect was also seen to a lesser extent with the unoxidised fatty acids. However, addition of the products to a phospholipid preparation potentiated its thrombin generating activity, indicating the release of phospholipid is not the only mechanism. The products showed marked inhibition of antithrombin III, which would result in increased amounts of thrombin being generated in plasma.Fractionation of the products showed that the highest activity was in the most polar fractions, and the activity was inhibited by horseradish peroxidase, suggesting that peroxide groups are involved.These studies indicate that lipid peroxides produced by non-enzymic means have potent effects on the plasma coagulation system, and suggest the possibility that the endoperoxides produced enzymically by platelets could also be involved in plasma coagulation.
The Anti-Xa Activity Of Lipoproteins
Authors: Barrowcliffe T W , Eggleton C A 
Published: July 2018

The major plasma inhibitor of Factor Xa is thought to be antithrombin III (At III). However, adsorption of plasma by aluminium hydroxide [Al(OH)3) increases its rate of Xa neutralisation 7-8 fold, and this ‘fast-acting’ anti-Xa activity has been shown to be independent of At III. We have carried out studies to determine the nature of the plasma components responsible for this increased anti-Xa activity after adsorption by Al(OH)3.Gel filtration of plasma indicated that the anti-Xa activity after Al(OH)3 adsorption was located largely in the high molecular weight (> 200,000) fractions. These fractions contain most of the plasma lipoproteins, and previous reports have indicated a connection between anti-Xa activity and lipoproteins, particularly those of low density. Purified very-low-density (VLDL), low-density (LDL) and high density (HDL) lipoproteins were prepared by ultracentrifugation, and characterised by polyacrylamide gel electrophoresis, cholesterol and phospholipid analyses. The lipoproteins were checked for lack of contamination with At III and α2-macroglobulin, and their anti-Xa activities measured before and after Al(OH)3 adsorption.LDL had a small but significant anti-Xa activity which increased with concentration; VLDL and HDL had virtually no activity. After Al(OH)3 adsorption of the lipoproteins, the activities increased, LDL giving the highest activity. Delipidation of the adsorbed LDL with fumed silica removed its anti-Xa activity.These results suggest that lipoproteins, especially LDL, contain binding sites for Factor Xa. The binding sites are related to the lipid content of the lipoproteins, and are exposed by Al(OH)3 adsorption. The fast-acting anti-Xa activity produced by Al(OH)3 adsorption of plasma is largely due to LDL.