bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexualbezogene Online-Fortbildung für Fachkräfte: Webvideos
Authors: Döring Nicola
Published: June 2018

Dieser Praxisbeitrag stellt verschiedene Formen von Webvideos vor und geht vor allem auf die Videoplattform YouTube ein. Er erläutert exemplarisch, welche Arten von YouTube-Videos zur sexualbezogenen Online-Fortbildung von Fachkräften nützlich sein können. Vorgestellt werden sexualbezogene Fachvorträge und Sexualberatung auf YouTube, jeweils mit unterschiedlichen thematischen Schwerpunkten. Zudem wird auf YouTube-Videos von Fachinstitutionen eingegangen und beispielhaft auf die Repräsentation von Trans* auf YouTube.
A Crystalline Ready-to-Use Form of Cyclopentadiene
Authors: Richert Clemens , Krupp Felix , He Shiliang , Frey Wolfgang
Published: June 2018

Cyclopentadiene (Cpd) is widely used as a starting material in organic and inorganic chemistry. In neat form, Cpd dimerizes, making it necessary to distill it prior to use to obtain fully reactive material. We have screened three different tetraphenyladamantane octaethers for their ability to act as encapsulating organic crystal (EnOC) hosts for Cpd. To this end, we also synthesized 1,3,5,7-tetrakis(3,5-dimethoxyphenyl)adamantane, a new octaether, dubbed iso-TDA. Only one of the octaethers was found to produce inclusion complexes with Cpd in the crystalline state. The encapsulated diene was stable for one month and showed full reactivity in a series of different synthetic transformations.
Identification of a Glycoprotein III a Dimer in Polyacrylamide Gel Separations of Human Platelet Membranes
Authors: Calvete J J , McGregor J L , Rivas G , González-Rodríguez J
Published: June 2018

Membrane glycoproteins IIb and IIIa play a major role in human blood platelet aggregation. The absence or the severe reduction of these two membrane glycoproteins, as observed in platelets of Glanzmann’s thrombasthenic patients, is related to a lack of platelet aggregation. Separation of Glanzmann’s thrombasthenic platelet samples by two-dimensional polyacrylamide O’Farrell gels show the absence of a high and several low molecular mass glycoproteins, in addition to the loss of glycoproteins IIb and IIIa (McGregor J. L. et al. Eur. J. Biochem. 1981; 116: 379-388). The aim of this study was to identify the nature of the high molecular mass component, absent in thrombasthenic platelets. A high molecular mass glycoprotein (200 kDa), present in two-dimensional SDS-polyacrylamide O-Farrell gel separations, was recognized by a monoclonal antibody (MP37) directed against glycoprotein IIIa. Moreover, the tryptic peptide map of this high molecular mass glycoprotein was nearly identical to that of glycoprotein IIIa. These results indicate that this high molecular mass glycoprotein present in SDS-polyacrylamide gels is a dimer of glycoprotein IIIa. This work raises the possibility that the high molecular mass glycoprotein, absent in two-dimensional O’Farrell gel separations of thrombasthenic platelets, is a dimer of glycoprotein IIIa.
Abnormal Structure of von Willebrand Factor in Myeloproliferative Syndrome Is Associated to Either Thrombotic or Bleeding Diathesis
Authors: López-Fernández M F , López-Berges C , Martín R , Pardo A , Ramos F J , Batlle J
Published: June 2018

The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.

The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.
The Platelet Volume Distribution: A Signature of the Prethrombotic State in Coronary Heart Disease?
Authors: Trowbridge E A , Martin J F
Published: June 2018

A coronary care unit population of 175 consecutive patients was studied. A clinical diagnosis of acute myocardial infarction was made in 103 cases (MI group) while 72 had chest pain, ECG indications of myocardial ischaemia, but no other clinical signs of acute myocardial infarction (control group). Based on bivariate Gaussian statistics the MI group could be divided in two groups, with respect to the platelet parameters of count and volume. The majority (65%) had large mean platelet volume and low count, while the remainder were indistinguishable from the control group. Patients with a large mean platelet volume also had significantly different volume distributions when assessed for volume dispersion, asymmetry and convexity. It is argued that this platelet volume distribution provides a signature for the prethrombotic state in ischaemic heart disease. Identification of such a platelet signature in a patient with coronary artery disease may allow appropriate prophylactic action to be taken and reduce the risk of subsequent acute myocardial infarction.
Activation of Purified Prothrombin in Ammonium Sulfate Solutions: Purification of Autoprothrombin C
Authors: Seegers W. H , Heene D. L , Marciniak Ewa
Published: June 2018

For the generation of autoprothrombin C activity from prothrombin preparations in concentrated ammonium sulfate solution the optimum conditions were found to be near 2 M at pH 7. In addition to thrombin and autoprothrombin C an inhibitor was obtained. Methods were developed to obtain the autoprothrombin C consistently with a specific activity of about 4,700 units per mg protein, and a yield of one mg per liter of bovine plasma. At an intermediate stage of purification the stability of autoprothrombin C was far better than in the final product which lost activity even by simple freezing and thawing. Preservation of activity in 50% glycerol solutions at pH 7.2 was found to be the most convenient procedure. The alterations produced in purified prothrombin with DEAE cellulose chromatography are discussed with respect to possible significance for thrombin and autoprothrombin C.
Studies on the Mechanism whereby Platelets are Clumped by Adenosine Diphosphate
Authors: Spaet Th. H , Lejnieks Ilze
Published: June 2018

The effect of platelets on C14-labeled adenosine diphosphate (ADP) was studied. It was found that :

1. A small amount of radioactive ADP in platelet-rich plasma became irreversibly bound to platelets, but on extraction radioactivity was found as a conversion mixture of adenine nucleotides resembling that in the platelet pool. Red cells showed similar binding and conversion, but only platelets were clumped by ADP. Nucleotides with little or no clumping activity (ATP, AMP and adenosine) bound to platelets and red cells in a manner similar to that of ADP, and they also yielded similar intracellular conversion products.

2. Platelet-poor plasma converted ADP into adenosine monophosphate (AMP), but this activity was destroyed at 56° C in 10 minutes. Heated, platelet- poor plasma was a suitable medium for washing and suspending platelets in these studies.

3. Platelets washed and suspended in heated plasma were clumped by ADP and produced ADP-dephosphorylation only in the presence of divalent cation. Red cells showed no ability to dephosphorylate ADP in this system.

4. Platelets washed in saline or studied in the presence of excess AMP were not clumped by ADP nor did they yield ADP-dephosphorylation. Benadryl inhibited platelet clumping, but was without effect on ADP-dephosphorylation.

It is suggested that ADP clumps platelets by serving as an energy source to activate a binding reaction as yet unidentified.
Incorporation of Labelled Nucleotides and Aggregation of Human Blood Platelets
Authors: Salzman E. W , Chambers D. A , Neri Lena L.
Published: June 2018

Addition of ADP-8-C14 to platelet-rich plasma results in platelet radioactivity through a series of temperature-dependent reactions involving stepwise dephosphorylation of the nucleotide in plasma and then incorporation of the adenosine residue by the platelet, where it participates as a precursor in synthesis of platelet adenine nucleotides. This sequence of events, which requires a heat-labile nondialysable plasma factor, is blocked by 0.01 M KCN, by EDTA, by arginine methyl ester, by adenosine, and by AMP.

ADP-induced platelet aggregation does not require the reactions outlined above and proceeds without ADP - breakdown and without binding of the ADP- molecule to the platelet. A possible mechanism of this phenomenon is suggested.
Some Effects of Low Molecular Weight Dextran on Coagulation
Authors: Dugdale Marion , Nofzinger J.D , Murphey F
Published: June 2018

LMDX has been shown to affect adversely the rate of prothrombin consumption during coagulation and the structure of the fibrin clot when present in the concentrations usually recommended for clinical use. Its use in animals with hemostatic defects induced by the pump-oxygenator was accompanied by excessive bleeding. At the same time, however, it conferred some form of protection which led to improved survival. A manner of using LMDX so as to benefit from its protective action without endangering hemostasis is currently under study.
Effects of Epsilon-Aminocaproic Acid on Fibrin Clot Lysis
Authors: Egeblad K
Published: June 2018

The inhibitory effect of EACA on plasmin, urokinase, and SK-activator was investigated by means of fibrin clot lysis. Clot formation and resolution was followed by thrombelastography.

Lysis of the simple fibrin clot by plasmin is inhibited by low concentrations of EACA. There is a dual effect of EACA on urokinase induced fibrinolysis. Low concentrations of EACA enhanced, whereas high concentrations inhibited urokinase activity. Assayed in the simple fibrin clot the SK-activator was the most sensitive to EACA inhibition, urokinase fibrinolysis the least.

Several factors influence the inhibitory effect of EACA, and the effect depends on the fibrinolytic agent used. The inhibitory effect of EACA on urokinase was strongly potentiated by a plasma factor present in the euglobulin fraction. The effect of EACA on SK-activator was only slightly potentiated by the plasma factor, and there was no effect on plasmin inhibition.

In presence of the urinary trypsin inhibitor mingin the inhibitory effect of EACA on urokinase induced fibrinolysis was enormously increased and the enhancing effect of EACA was reversed. Assayed against SK-activator the effect of mingin was less pronounced, and was only slight when assayed against plasmin. The inhibitory effects of the soy bean trypsin inhibitor, the ox lung trypsin inhibitor pulmin, and the pancreas inhibitor of Kunitz on the urokinase fibrinolysis were all slightly decreased in presence of EACA.

The thrombin generation in recalcified human plasma, the tissue thromboplastin time, and the thrombin time were all unaffected by even high concentrations of EACA, However, in the thrombelastographie assay, EACA influenced fibrin formation or structure when present together with activators of plasminogen.

The multiple effects of EACA on fibrinolysis makes it difficult to elucidate its action in vivo.
Effect of Dextrans in Vitro on the Adenosine Diphosphate Induced Adhesiveness of Human Blood Platelets
Authors: Bygdeman S , Eliasson R
Published: June 2018

The effect of adding dextrans with Mw from 40,000 to 153,000 to blood samples on the ADP induced platelet adhesiveness to glass has been studied. It was observed that a dextran concentration in the plasma of 1 % did not change the adhesiveness, while a concentration of 1.5 and 2% caused a slight increase. The results make it less likely that the decreased tendency of the platelets to aggregate in vivo after dextran treatment, as described by other authors, is due to an effect on the ADP reactive receptors located on the surface of the platelets.
A Device for the Production of Well-Defined Lesions of Mesenteric Blood Vessels with Resulting Platelet Thrombi
Authors: Reber K
Published: June 2018

Well-defined lesions of mesenteric blood vessels with resulting platelet thrombi are produced in a reproducible manner by electric stimulation with a microelectrode under microscopic observation. The apparatus used and the results obtained are described.
Effects of Dimethyl Sulphoxide and of Vitamin A on Human Platelets
Authors: Davey M. G , Lüscher E. F
Published: June 2018

Dimethyl sulphoxide (DMSO) causes some release of amino acids, adenine nucleotides, and acid phosphatase and β-glucuronidase activities from washed human platelets. Addition of vitamin A with DMSO greatly enhances the effect; but vitamin A in ethanol added to platelets fails to release amino acids and nucleotides. Release appears to be due to a change in permeability of the platelet membrane, not to the discharge of contents of intracellular structures. Lipid peroxidation of membrane phospholipids, or a similar reaction, may be involved. Thrombin causes a different type of alteration in platelet permeability.

The results suggest that DMSO should not be used as a preservative for platelets. They may have some bearing on the mechanisms of toxicity of DMSO and vitamin A.
Variation in ADP-Induced Platelet Aggregation in Vitro in Primates as a Result of Differences in Plasma ADP Inhibitor Levels
Authors: Hawkey C. M , Symons C
Published: June 2018

ADP-induced platelet aggregation and its reversal has been studied in platelet rich plasma of 25 non-human primates of 10 different species under standardised conditions. A wide variation in response to ADP in monkeys of different species has been found. A method is described for measuring ADP-splitting enzymes in plasma and using this method, a correlation has been found between reversal of ADP induced platelet aggregation and high levels of plasma ADP inhibitor. The results obtained are consistent with the hypothesis that variation in response to ADP of platelet-rich plasma is a result of differences in levels of plasma ADP-splitting enzymes.
The Effect of Imidazole upon Platelets Incubated in Vitro
Authors: Rossi E. C
Published: June 2018

Rat platelets were incubated in either balanced salt solution (BSS) buffered with imidazole, in plasma or in a third medium composed of BSS and plasma in a volume to volume mixture. Platelets incubated in imidazole BSS showed a more rapid decline in platelet count, earlier appearance of platelet clumping, greater consumption of glucose, greater production of lactic acid and CO2, and more rapid turnover of 32Pi. Platelets incubated in plasma showed less pronounced changes in these parameters while platelets incubated in imidazole BSS: plasma showed effects that were intermediate in degree to those observed with imidazole BSS or plasma alone. The possibility that these effects are related to the depletion of platelet ATP by imidazole is discussed.
The Release of ADP from Red Blood Cells
Authors: Rørvik T. O , Holmsen I , Stormorken H
Published: June 2018

The content of the adenine nucleotides, ADP and ATP, in whole blood from normals, patients with von Willebrand’s disease and diabetics was found to be equal. The hemolysis and AN-release from blood cells by contact with foreign surface were studied by passing blood through glass bead columns. The AN-release induced in this way was shown to be a hemolysis-related phenomenon, AN and hemoglobin were released in the same proportion as they were found within red cells. The hemolysis and AN-release induced in this way were nearly the same in blood from normals, patients with von Willebrand’s disease and diabetics.

Thrombin did not induce hemolysis or release of AN from red blood cells, whereas the release of AN from platelets by thrombin was confirmed.
The Activity of Plasma, Serum, Thrombin, and Plasmin toward Synthetic Trypsin Substrates
Authors: Szczeklik E , Orłowski M , Szczeklik A , Narczewska Barbara
Published: June 2018

P-toluenesulphonyl-1-arginine methyl ester and two amide substrates of arginine (Nα-benzoyl-dl-arginine-p-nitroanilide and Nα-benzoyl-dl-arginine-2-naphthylamide) were employed for studies of the nature of the “trypsin-like” activity in plasma, serum and euglobulins. No data were obtained which might suggest the presence of trypsin activity in either plasma or serum. The evidence indicates that activity toward both amide substrates in plasma and euglobulins is dependent on the generation of thrombin. Activation of plasminogen in euglobulins by streptokinase generated a proteolytic activity toward Nα-benzoyl-dl-arginine-p-nitroanilide but not toward Nα-benzoyl-dl-arginine-2-naphthylamide. The generation and inactivation of thrombin activity in whole plasma may be conveniently followed by using Nα-benzoyl-dl-arginine-p-nitroanilide as substrate.

Purified preparations of thrombin and plasmin were shown to split several synthetic amide substrates of arginine. Significant differences between thrombin and plasmin were found in the rate of reaction with these substrates. Of the amide substrates, Nα-carbobenzoxydiglycyl-l-arginine-2-naphthylamide was split most rapidly by both enzymes. This substrate may be conveniently used for the determination of thrombin and plasmin activity.
Modified Method for the Preparation of Purified Bovine Prothrombin of High Specific Activity
Authors: Malhotra O. P , Carter J. R
Published: June 2018

A modified method for the isolation and purification of bovine prothrombin is described. The preparations have a very high specific activity, viz. 3,200 ± 200 u/mg of protein, show a single symmetrical peak in the analytical ultracentrifuge and by moving boundary electrophoresis at both pH 6.86 and 8.6. They do not undergo inactivation or dissociation during electrophoresis at high voltage gradient (7.5) at alkaline pH. Disc electrophoresis also shows essentially a single component. For optimal activation, prothrombin requires the presence of factor VII-X complex in addition to factor V.
Effect of Fibrinolysis on Adhesion and Aggregation of Human Platelets
Authors: Cronberg S
Published: June 2018

Streptokinase was infused in 7 patients with venous thrombosis. The bleeding time remained unchanged or slightly prolonged and the number of platelets did not decrease. As studied by photometric technique, platelet aggregation after addition of ADP or connective tissue suspension was not consistently changed. Platelet adhesiveness, as tested with Hellem’s whole blood method, was decreased. The platelets showed decreased adhesion and spreading on a glass slide.

Addition of streptokinase in vitro to citrated platelet rich plasma in doses of 1,600–7,000 u/ml caused a release reaction after 2–3 min, and the platelets aggregated. Incubation with urokinase impaired adhesion to glass and spreading and slightly diminished aggregation by ADP or connective tissue suspension.

Purified split products of D, E or high molecular type in final concentrations of 0.1–2.0 mg/ml did not aggregate platelets or influence aggregation by ADP or connective tissue suspension. A slightly decreased adhesion to glass and spreading occurred only when the doses used were large.

The implications of the multifacetted findings are discussed.
Experimental Thrombocytopenia Induced by Busulphan (Myleran) in Rabbits: Extremely Low Platelet Levels and Intact Plasma Clotting System
Authors: Evensen S. A , Jeremic M , Hjort P. F
Published: June 2018

The effects of 2 intraperitoneal injections of the alkylating agent Busulphan (each of 25 mg/kg body weight, 3 days between injections) on the circulating elements of the blood and on the plasma coagulation system in rabbits have been investigated.

Platelets fell progressively after a lag-phase of 7 days, reached a mean minimum level of about 3 % of the pre-injection level in 14 days, and then returned slowly towards normal values. Bleeding was an occasional complication and a rare cause of death. Granulocytopenia developed synchronously with the fall in platelets. The plasma clotting factors remained intact.

We conclude that this is a useful experimental model for studies on the role of platelets in hemostasis and thrombosis.
Différents états moléculaires du facteur II (prothrombine). Leur étude à l’aide de la staphylocoagulase et d’anticorps anti-facteur II
Authors: Prou-Wartelle Odette , Soulier J. P ,   avec l’assistance technique de LILIANE HALLÉ
Published: June 2018

Le passage du plasma humain décalcifié au travers de filtres d’amiante entraîne une modification de la structure moléculaire du facteur II. Les activités biologiques du facteur II se trouvent dissociées: diminution de l’activité prothrombine et augmentation importante de l’activité prothrombine-coagulase. Ce phénomène est expliqué par une diminution de l’affinité du facteur II envers la prothrombinase physiologique, une augmentation de son affinité envers la staphylocoagulase. Ces modifications des activités biologiques du facteur II vont de pair avec un changement de certaines de ses propriétés physico-chimiques qui se rapprochent de celles de la thrombine (caractères d’adsorption, mobilité électrophorétique).
Immune Reactions of Human Blood Platelets
Authors: Mueller-Eckhardt Ch , Lüscher E. F
Published: June 2018

The effects on washed human blood platelets of heterologous antiplatelet antiserum, antigen-antibody complexes, and aggregated human gammaglobulin have been compared with those of thrombin. The following results were obtained:

1. Heat-aggregated gammaglobulin and antigen-antibody complexes affected platelets in much the same way as does thrombin; they caused release of adenine nucleotides, aggregation, and contraction of the formed aggregates. Their effect is not inhibited by the presence of hirudin.

2. Anti-platelet antisera (rabbit) gave rise to similar reactions of the platelets, whereby quantitative differences between individual antisera were evident.

3. Release of nucleotides by all types of agents tested is a fast process; at 37° C the major part is released during the first minute.

4. Whereas Ca++-ions are essential for aggregation and concentration of the aggregates, their presence is not necessary for the release-reaction induced by immune agents or thrombin.

5. Calculated on a protein basis, thrombin is twice as efficient as a nucleotide releaser as heat-aggregated gammaglobulin; on a molecular basis, therefore, the gammaglobulin-preparation is more effective.

6. Only immune agents capable of activating the complement system exert an influence on platelets; but neither is the addition of complement necessary, nor was it possible to detect complement on or in the platelets. The possibility is discussed that platelets might possess receptors capable of reacting with C’-activating immune agents, and that this represents a type of cellular reaction which is independent of the activation of plasmatic complement.
Wirkungen oligomerer Kationen auf die Blutgerinnung
Authors: Herre Veronika , Frimmer M
Published: June 2018

1. Das Polykation Oligo-N-methyl-morpholiniumpropylenoxid (OMP) hebt die Heparinwirkung auf die Blutgerinnung in vivo und in vitro konzentrationsabhängig auf.

2. OMP mit 6 bzw. 10 quartären Untereinheiten (OMP-6 und OMP-10) beeinflußt selbst die Gerinnungszeit. Es verlängert bzw. verkürzt die Gerinnungszeit konzentrationsabhängig (geprüft an der Rekalzifizierungszeit von Humanplasma und der Gerinnungszeit in einem Thrombin-Fibrinogen-System). Intravenös verabreichte Dosen von OMP-10 unter 50 mg/kg Körpergewicht beeinflussen beim Kaninchen die Gerinnungszeit nicht. Tödliche Dosen verlängern die Gerinnungszeit geringfügig.

3. Die klinische Anwendung des Polykations ist aus toxikologischen Überlegungen nicht ratsam.

4. Der Wirkungsmechanismus des OMP auf die Blutgerinnung wird diskutiert.
On the Nature of Antithrombin V
Authors: Vinazzer H , Reinhardt F
Published: June 2018

Two cases of myeloma with a severe bleeding tendency due to the occurrence of antithrombin V could be observed. The following data on this inhibitor were collected:

1. The inhibitor activity could be temporarily suppressed by long term treatment with cortisone. The long lag period indicates that a cellular function must be responsible for the production of antithrombin V.

2. Various tests confirmed that antithrombin V is a true inhibitor of thrombin and not a polymerization inhibitor.

3. The esterase activity of thrombin is not inhibited by antithrombin V.

4. The reptilase activity is reduced by antithrombin V.

5. Highly concentrated antithrombin V could be extracted from a patient’s bone marrow. This led to the assumption that the bone marrow participates in the production of antithrombin V.

6. Sephadex fractionation of the serum revealed that the entire antithrombin V activity moves with the A-fraction.

7. On ultrafiltration, the antithrombin activity remained on the diaphragm, indicating that antithrombin V is a true protein and not a split product.
Inhibition by Dipyridamole of Arterial Thrombosis in Rats
Authors: Didisheim Paul
Published: June 2018

Thrombi in mesenteric arteries of the rat were produced by electric means. The effectiveness of 4 agents – heparin, aspirin, warfarin, and dipyridamole – in modifying arterial thrombosis was examined with this model. Heparin and aspirin had equivocal beneficial effects. Warfarin had a deleterious effect: the duration of complete occlusion was prolonged. In striking contrast, dipyridamole induced a marked shortening in the duration of complete thrombotic occlusion. On reinjection of the drug, occlusion was almost completely suppressed.
Treatment of Thrombosis of the Central Retinal Vein with Streptokinase
Authors: Ottolander G. J. H den , Craandijk A
Published: June 2018

In a double blind study of 5 heparin treated and 5 streptokinase treated patients with central retinal vein occlusions it would seem from the results based on visual acuity, ERG and EOG and fluorescence angiography that the heparin treated group were better off than the SK treated patients.

It therefore seems dubious whether streptokinase therapy affords such an important advantage over the convential heparin therapy in cases of central retinal vein occlusions. It must be stressed that a group of 10 patients is very small and that the observations made are probably not statistically significant.
Endotoxin-Induced Intravascular Clotting: the Need for Granulocytes
Authors: Lerner R. G , Rapaport S. I , Spitzer Jane M.
Published: June 2018

This study was undertaken to test the hypothesis that granulocytes are needed for intravascular clotting induced by endotoxin. Rabbits were treated with cortisone in a dosage that prepares for clotting after a single injection of endotoxin. They were divided into an experimental group, made granulocytopenic with nitrogen mustard before the injection of endotoxin, and 3 control groups. One control group was injected with saline; a second group was injected with endotoxin; a third group was made hypo coagulable with warfarin before the injection of endotoxin. The controls receiving endotoxin alone exhibited evidence of slow intravascular clotting lasting several hours: excess intravascular disappearance of 131I-fibrinogen and falls in fibrinogen levels, platelet counts, factor V and factor VIII activities. Factor VII and factor XII activities also fell in this group. Fibrin was seen in glomerular capillaries in many animals. The granulocytopenic animals experienced neither excess disappearance of intravascular fibrinogen nor fibrin deposition in the kidneys. Platelet counts fell slowly and clotting factor activities only slightly. Less evidence of intravascular clotting after endotoxin was found in the granulocytopenic animals than in the animals made hypocoagulable with warfarin. These data establish that granulocytes are required for endotoxin to induce significant intravascular clotting in animals prepared with cortisone.
Das Verhalten des Blutgerinnungsfaktors X (Stuart-Prower) aus Plasma und Serum bei der Gelfiltration an Sephadex G 200
Authors: Rasche H , Hiemeyer V , Heller A
Published: June 2018

Menschliches und bovines Plasma und Serum wurde an Sephadex G 200 aufsteigend chromatographiert und in den Fraktionen die Faktor-X-Aktivität bestimmt. Faktor X aus Plasma wurde in allen Fällen schneller aus der Säule eluiert als der gleiche Faktor aus Serum. Aus diesem Befund kann auf eine während der Blutgerinnung aufgetretene Molekülverkleinerung des Proteins geschlossen werden, welches die Faktor-X-Aktivität trägt. Unsere Ergebnisse werden im Rahmen der zu dem Thema vorliegenden Literatur diskutiert.
Cholecystectomy in a Patient with Hageman Trait
Authors: Girolami A , Maffei A , Brunetti A , Lazzarin M
Published: June 2018

The case of a patient with Hageman trait who underwent cholecystectomy for cholelithiasis is reported. The surgical procedure was uneventful; no abnormal bleeding was noted during and after the operation. The transfusion of 4 cm3/kg b.w. of contacted 3-day old normal plasma corrected completely the coagulation abnormality. The glass and the silicone clotting times were slightly shortened even 64 h after the transfusion. The survival time for the infused factor XII activity resulted to be 41 h. 6 days after the plasma infusion the factor XII level was 1 % of normal. The significance of these findings is discussed.
Inhibition of Thrombin, Plasmin and Plasminogen Activation by Amidino Compounds
Authors: Geratz J. D
Published: June 2018

1. A series of amidino compounds have been investigated for their inhibitory effect on thrombin, plasmin and the streptokinase dependent activation of plasminogen. Diamidines composed of two amidinophenyl residues linked in para or meta position by a molecular bridge proved to be the strongest inhibitors known so far of the three enzyme systems, and they were much more active than amidines with a single-ring structure.

2. Of all the compounds tested, pentamidine was the most effective inhibitor of the hydrolysis of BANA by thrombin and plasmin. The Ki values were 9 × 10-6 M and 3.3 × 10-6 M, respectively. Inhibition was competitive in nature.

3. Pentamidine was the leading inhibitor of the fibrinolytic activity of plasmin and was approximately 83 times stronger, on a molar basis, than ε-aminocaproic acid.

4. Pentamidine also possessed the greatest inhibitory effect on the streptokinase-mediated activation of human plasminogen. On a molar basis pentamidine was 910 times more active than ε-aminocaproic acid.

5. In the thrombin clotting test, some amidines caused inhibition while others brought about an acceleration of the reaction. M & B 4596 was the strongest inhibitor affecting 50% inhibition at a concentration of 5 × 10-6 M. 2.2’-Dibromopropamidine produced the greatest augmentation of thrombin activity, raising it 167% above the control level at a concentration of 2 × 10-4 M.

6. The caseinolytic activity of thrombin again was blocked most effectively by M & B 4596. All other amidines also proved inhibitory in this assay system.
A Simple Procedure for Accurate Quantitation of Factor VIII Inhibitors
Authors: Tse Daphne , Fekete L , Shanbrom E
Published: June 2018

A simple assay for quantitative determination of factor VIII (AHF) inhibitors has been developed. The presence of AHF inhibitor is confirmed by determining clotting time in serial dilutions of patient’s plasma. The amount of inhibitor is then quantitat-ed by adding known units of human AHF concentrate (1 to 100 units/ml) to plasma until neutralization occurs. The neutralization point is defined as that level of AHF concentrate which clots the patient’s plasma in the same time as the control plasma (inhibitor-free) would clot in the presence of 1 unit of AHF concentrate. (This point, minus the initial 1 unit/ml, gives the titer of inhibitor present (units/ml). The dosage of AHF concentrate required to overcome the inhibitor and raise the free circulating AHF to the desired theoretical level is then calculated from the known titer of inhibitor. This method has been evaluated by assays of 75 samples from 22 patients with acquired or induced AHF inhibitors. In vivo plasma AHF activity correlated well with the calculated in vitro values. The assay provides reliable and accurate quantitation of factor VIII inhibitors enabling precise calculation of effective AHF dosage and monitoring of therapeutic response. The assay can be readily adapted to quantitation of other clotting factor inhibitors.
Über die Wirkung von Lipidemulsionen auf Blutplättchen
Authors: Weber E , Pfleiderer Th , Feder U , Morgenstern E
Published: June 2018

Blutplättchen vom Schwein, bei 37° C in Zitratplasma suspendiert, wurden Emulsionen aus Lipiden und fettähnlichen Stoffen zugesetzt. Folgende Substanzen kamen zur Anwendung : Leinöl, Lipofundin, Triolein, Ölsäure, Ölsäuremethylester, Paraffin und Silikonöl. Es wurden die stationären Konzentrationen an ATP und Glykogen sowie der Glukose ver brauch der Platt chen gemessen. Alle genannten Stoffe außer Silikonöl führten zu starken Verlusten an ATP sowie Glykogen und erhöhten den Glukoseverbrauch. Beide Plättchenkomponenten veränderten sich unter dem Einfluß von Leinöl oder Lipofundin gegenüber Kontrollen nicht, wenn die Zellen in EDTA-Plasma suspendiert waren oder wenn dem Zitratplasma EPL oder Albumin zugesetzt worden war. Auch chromatographisch gereinigtes Triolein sowie Leinöl, aus dem die freien Fettsäuren entfernt worden waren, blieben ohne Einfluß auf den ATP- und Glykogenbestand. Adenosin verminderte den Leinöl- und Lipofundineffekt. Der Glukoseverbrauch war unter allen genannten Bedingungen erhöht.
Detection of Fibrinogen Degradation Products by Use of Antibody Coated Latex Particles
Authors: Melliger E. J
Published: June 2018

A method for rapid determination of fibrinogen split products in human blood basing on agglutination of antibody coated latex particles is described. It’s sensitivity corresponds to that of Ouchterlony plates (17 μg/ml plasma). The result is available within 1 hr after drawing of blood. The method is semiquantitative with a at least as good reproducibility as the haemagglutination inhibition method. The reaction kinetics follow the principle of optimal proportion in a precipitin system.

46 healthy people and 36 patients with various diseases were tested with the described method. 3 controls and 12 patients gave positive agglutination reactions that could not be attributed to the presence of split products. The mechanism of these side reactions which could be distinguished from the reactions due to fibrinogen degradation products is discussed. In the plasma of 10 patients split products could be demonstrated by the latex agglutination technic which was also successfully used to control the course of chronic intravascular coagulation in a patient with disseminated cancer of stomach. On account of the obtained results the method can be recommended as a fairly sensitive screening test for rapid bedside detection of fibrinogen degradation products.
Prostaglandins and Platelet Aggregation in Vivo
Authors: Kloeze J
Published: June 2018

It was shown previously that prostaglandin E1 (PGE1) inhibits the aggregation of blood platelets in vitro whereas PGF1α does not; in vivo, PGE1 inhibits in rats the action of intravenously injected adenosine diphosphate. Locally administered PGE1 is found in the present experiment to inhibit in rats the formation and growth of platelet thrombi, induced by an electric stimulus in cortical veins. PGF1α appeared to be inactive.

The morphology of platelet thrombi induced by an electric stimulus is shown. The probability of a primary role of erythrocytes in the formation of this type of thrombi is discussed.
The Preparation of an Artificial Reagent for the One-Stage Factor VIII Assay
Authors: Nyman D
Published: June 2018

A method for preparation of an artificial substrate for the one-stage factor VIII assay is described. Standardization of the test is given. The method is specific and reproducible.
Reversible Stadien intravaskulärer Gerinnung und ihre Auswirkungen auf Nierenfunktion und Urokinaseausscheidung
Authors: Theiss W , Graeff H , Bleyl U , Immich H , Kuhn W
Published: June 2018

Weiblichen Kaninchen wurde physiologische Kochsalzlösung, Thrombinlösung, Trasylol-Lösung und Trasylol-Thrombin gemeinsam infundiert. Hierbei waren nach Infusion von Thrombin und von Thrombin-Trasylol im Plasma wie in Gewebsschnitten Fibrinmonomere nachweisbar. Eine disseminierte intravaskuläre Gerinnung war bei den Tieren, die Thrombin-Trasylol kombiniert erhielten, deutlicher ausgeprägt als bei den Tieren, die nur Thrombin erhielten. Ein primär polyurisches akutes Nierenversagen war nur bei den Tieren nachweisbar, die Thrombin-Trasylol erhalten hatten. Tiere, die Thrombin erhalten hatten, wiesen gegenüber Kontrollgruppen eine relative Verminderung der Urokinaseausscheidung pro Minute im Urin auf. Die glomerulären Fibrinniederschläge werden während des Versuchszeitraumes von 20 Std. wieder aufgelöst und die beobachteten Veränderungen kehren gegen Versuchsende zu den Ausgangswerten zurück. Darüber hinaus kann im Urin spontan eine Inhibitoraktivität gegenüber Plasmin oder Piasminogenaktivator beobachtet werden, deren Ausscheidung mit steigenden Konzentrationsleistungen der Niere zunimmt. Nach Trasylol-Infusion tritt eine Inhibitoraktivität im Urin häufiger und in stärkerem Ausmaß auf, als dies spontan der Fall ist.

Die Annahme erscheint gerechtfertigt, daß reversible Stadien der disseminierten in tra va skulären Gerinnung, deren Quantität und Dauer vermindert ausgeprägt sind, Urokinaseausscheidung und Nierenfunktion vorübergehend beeinträchtigen, wobei die Veränderungen bei Wiederauflösung der Gerinnsel rückläufig sind.
Durch erhöhte Thrombozytenzahl kompensierte Thrombasthenie bei einem Probanden mit Pelger’scher Kernanomalie
Authors: Kuhnke E
Published: June 2018

Bei einem Probanden mit Pelger’scher Kernanomalie der Leukozyten wird eine Thrombozytose und eine Thrombasthenie festgestellt. Durch die Verwen dung des von uns für vergleichende Untersuchungen vorgeschlagenen Thrombozytenäquivalenzwertes und des »Retraktionsgrades in % der Norm« kann nachgewiesen werden, daß durch die Vergrößerung der Thrombozytenzahl die Thrombasthenie ausgeglichen wird. Dadurch fällt die Retraktion des Gesamtsystems normal aus.
A Congenital Inhibitor against Factor IX
Authors: STOCKER H
Published: June 2018

A new congenital hemorrhagic diathesis, which is due to the presence of a circulating inhibitor against factor IX, simulating a hemophilia B, is described. It is demonstrated, that the inhibitor becomes much less efficient when the factor VUI-concentration decreases. A hypothesis is given which should explain the role of factor VIII in the inhibition process.
Zur intravasalen Streptokinase-induzierten Thrombolyse bei der Maus Vitalmikroskopische und gerinnungsphysiologische Beobachtungen
Authors: Martin M , Hiemeyer V , Rasche H
Published: June 2018

1. Eine Versuchsanordnung, die es gestattet, auf elektrischem Weg Mikrothromben in den Ohrvenen der Maus zu setzen, ihre Rückbildung unter Zufuhr verschiedener thrombolytisch wirkender Medikamente vitalmikroskopisch zu verfolgen und photographisch festzuhalten, wurde beschrieben.

2. Gerinnungsphysiologische Untersuchungen des fibrinolytischen Potentials der Maus (Streptokinase-Resistenztest, Rinderfibrinplattentest und Thrombelastogramm) ergaben im Vergleich zum Menschen verhältnismäßig geringe streptokinase-induzierbare fibrinolytische Aktivitäten bei deutlicher Vermehrung der Inhibitoren.

3. Wurden die fibrinolytischen Faktoren der Maus durch Injektion von zitriertem Humanplasma angehoben, so war es möglich, die venösen Thromben im Ohr der Maus in 69 bis 85 % bei insgesamt 45 Tieren durch Streptokinasezufuhr vollständig aufzulösen. Dieses Ergebnis war im Vergleich mit einer unbehandelten Kontrollgruppe statistisch signifikant.

4. Die Beobachtung des Lysevorgangs unter dem Vitalmikroskop erlaubte Aussagen über morphologische Veränderungen am Thrombus während der Streptokinasebehandlung in vivo.

5. Während des gesamten intravasalen Thrombolyse Vorgangs war, wie Paralleluntersuchungen zeigten, auf Grund des besonders hoch liegenden Antiplasmintiters, keine freie Plasminaktivität nachweisbar.
Eine neue Methode zur Bestimmung der Plättchenhämostasekapazität
Authors: Kolde H.-J. , de Haan J.
Published: June 2018

Der Mangel des von-Willebrand-Faktors (vWF) stellt mit einer Prävalenz von >1% die häufigste kongenitale Gerinnungsstörung mit einer potentiellen Blutungsdiathese dar. Im Rahmen der konventionellen Gerinnungsanalytik werden jedoch dieser Mangel wie auch andere Störungen der Primärhämostase, z.B. durch Azetylsalizylsäure (ASS), oft nicht erkannt. Die schwierig zu standardisierende Blutungszeit wird häufig nicht durchgeführt und ihre Aussagekraft ist nicht unumstritten.

Eine neue Methode zur Bestimmung der Plättchenhämostasekapazität (platelet hemostatic capacity, PHC) mit dem PFA-100®, eine Weiterentwicklung der » In-vitro-Blutungszeit« nach Kratzer und Born, könnte hier eine diagnostische Lücke schließen. Dieser Globaltest untersucht die Fähigkeit einer Zitratvollblutprobe, unter hoher Scherkraft an einer Kollagenmatrix einen Thrombus zu bilden. Die dynamischen Verhältnisse ähneln den Bedingungen in der Mikrozirkulation. Ergebnisse aus In-vitro-Experimenten und klinische Untersuchungen zeigen, daß mit diesem Verfahren mit hoher Sensitivität sowohl ein Mangel des von-Willebrand-Faktors wie auch kongenitale Thrombozytopathien und durch ASS oder andere Ursachen induzierte Störungen der Thrombozytenfunktion erkannt werden. Die Meßwerte zeigen eine Übereinstimmung von >90 % mit der Aggregometrie, liegen aber bereits nach ca. 5 min vor und benötigen nur ca. 0,8 ml Blut. Nach ersten Ergebnissen ist die PHC bei Patienten mit Schlaganfall erhöht, ein erster Hinweis, daß mit diesem Verfahren möglicherweise nicht nur eine verstärkte Blutungsneigung, sondern auch eine Hyperaktivität der Thrombozyten nachweisbar ist.
Fibrinolytische Aktivität im Plasma vor und nach Tumorresektion
Authors: Hegazi E. , Seifert J.
Published: June 2018

Bei 50 Kontroilpatienten und 50 Patienten mit einem Tumor im Abdominalbereich wurde die fibrinolytische Aktivität mittels hochgereinigtem Testfibrinogen, welches frei von Plasminogen war, vor und nach der Operation bestimmt. Dabei wurde das Testfibrinogen in einer 1 %igen Lösung in Petrischalen gefüllt und mit 0,375 IU Thrombin zum Gerinnen gebracht. Auf diese Fibrinplatten wurden 0,01 ml des zu testenden Plasmas appliziert und der Lysehof nach 24 Stunden abgelesen. Zusätzlich wurden Fibrinogen, Fibrinogenspaltprodukte X und Y, α2-Makroglobulin, der Faktor V, der Quickwert, die partielle Thromboplastinzeit und die Plasma-Thrombinzeit mit üblichen Labormethoden bestimmt. Während bei den Kontroilpatienten die fibrinolytische Aktivität hoch ist und durch die Operation unbeeinflußt bleibt, liegt sie bei Tumorpatienten um 40% niedriger und wird durch die Entfernung des Tumors signifikant aktiviert. Die Konzentration des Fibrinogens steigt postoperativ sowohl bei Tumorals auch bei Kontroilpatienten an. Die Fibrinogenspaltprodukte X und Y, welche mittels Thrombinkoagulase gebildet werden, sind bei Tumorpatienten signifikant erhöht und steigen postoperativ um 60% an. Bei Kontroilpatienten bleiben sie durch die Operation unbeeinflußt. Bei allen übrigen gemessenen Parametern konnten keine Unterschiede zwischen Tumor- und Kontroilpatienten festgestellt werden. Die Bestimmung der fibrinolytischen Aktivität könnte somit als zusätzliche Information für das Vorhandensein von malignen Tumoren eingesetzt werden oder auch für das Auftreten von Tumorrezidiven. Darüber .hinaus können daraus Rückschlüsse für eine notwendige Antikoagulanzientherapie gezogen werden.
Blutgerinnungsstörungen im Tiermodell
Authors: Rieger M , Schwarz H.P , Turecek P.L , Mannhalter Christine
Published: June 2018

Um neuentwickelte Präparate zur Behandlung von Patienten mit Blutgerinnungsstörungen in ihrer Wirkung einschätzen zu können, ist die Evaluierung in Tiermodellen unerläßlich. Dazu eignen sich eine Reihe unterschiedlicher Tiere. Vor allem Schweine, Mäuse und die in diesem Artikel näher beschriebenen Hunde sind sicher die wichtigsten Tiermodelle zum Studium der von-Willebrand-Erkrankung.

Ein besonders gut charakterisiertes Tiermodell einer vW-Typ 3-Erkrankung ist das Schwein. Einige Schweinefamilien sind schon seit langem bekannt, sind gut dokumentiert und auch phänotypisch genau definiert. Durch Kopplungsanalysen konnte gezeigt werden, daß der Defekt, der für den vWF-Phänotyp bei den kranken Tieren verantwortlich ist, im vWF-Gen lokalisiert sein muß. Die kausale Mutation wurde bis jetzt jedoch nicht identifiziert.

Hunde zeigen in der Charakteristik des Proteins und der cDNA-Sequenz des vWF mit dem Menschen eine weitgehende Übereinstimmung. Im Jahr 1995 wurde von Slappendel erstmals eine Hundefamilie mit einer Typ-3-vWF-Erkrankung beschrieben. Die betroffenen Tiere haben kein detektierbares vW:Ag, keine nachweisbaren vWF-Multimere und reduzierte Faktor-VllI-Spiegel.

Durch eine genaue genetische Untersuchung dieser Tiere konnte die kausale Mutation, eine homozygote Splice-site-Mutation an der ersten Stelle im Intron 16 identifiziert werden. Die Mutation führt zur Entstehung eines Stop-Codons und dem Abbruch der Proteinsynthese.

Daher sind diese Hunde ein hervorragendes Modell, um einen Wirkstoff zur Behandlung der von Willebrandschen Erkrankung auszutesten.
Anticoagulation Strategies in Ischemic Stroke: Evidence Based on Experimental Research
Authors: del Zoppo G. J.
Published: June 2018

Anticoagulation has not been shown unequivocally to confer benefit to patients with TIAs, stroke-in-evolution, partial stable stroke, or completed stroke. One unconfirmed study of subcutaneous LMWH (nadroparin) applied in early stroke appears to reduce mortality at 6 months. Anticoagulation has been shown to significantly decrease the frequency of cerebral embolism in patients with a signal myocardial infarction, atrial fibrillation in the absence of a valvular abnormality, and mechanical cardiac valve prosthesis, or xenograft (bio)prostheses. The use of LMWH or low molecular weight heparinoids to reduce stroke-related disability and/or mortality is currently under rigorous study, although outcomes are conflicting. However, the contributions of fibrin and platelet deposition to microvascular occlusion following middle cerebral artery occlusion provides an experimental basis for considering the use of antithrombins to maintain microvascular patency and therefore potentially reduce tissue injury during acute focal cerebral ischemia.
Studies on the Pathogenesis of the Generalized Shwartzman Reaction
Authors: Rodríguez-Erdmann F
Published: June 2018

Animals treated in the conventional form to elicit the generalized Shwartzman reaction (gSr) by means of properly spaced injections of endotoxin develop an abrupt consumption of the plasmatic factors of the clotting mechanism, as demonstrated by the reduction of the activity of prothrombin and Ac-G (factor V). These animals show ultimatly characteristic morphological pattern: bilateral cortical necrosis of the kidney. Rabbits treated four hours after the second (‘‘provocative”) endotoxin injection with streptokinase (Varidase/Lederle) in order to activate the fibrinolytic system failed to develop the renal cortical necrosis, but their prothrombin and Ac-G (factor V) level decreased abruptly.

Through indirect deduction the intravascular presence of thrombin-like activity is accepted four hours after the “provocative” endotoxin injection.