bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical and Functional Study of Antithrombin III in Newborn Infants
Authors: McDonald M M , Hathaway W E , Reeve E B , Leonard B D
Published: July 2018

Antithrombin III (AT-III) was isolated by heparin affinity chromatography from adult venous and newborn term and preterm umbilical cord blood. The purified proteins were compared by SDS-PAGE, rocket immuno-electrophoresis, protein concentration by microbiuret relative to optical density at 280 nm, heparin cofactor specific activity, progressive neutralization of thrombin and factor Xa at 37°C and pH related antithrombin kinetics. The structural evaluations revealed a fetal AT-III of molecular weight, charge and electrophoretic migration indistinguishable from adult AT-III. The functional studies showed that, on an equimolar basis, the rates of thrombin and Xa interactions with fetal AT-III were as rapid as those with adult AT-III. The catalytic rates of various concentrations of heparin were also equal. The newborn infant, therefore, displays a quantitative but not qualitative deficiency of AT-III.
Activation of Human Coagulation Factor VIII by Activated Factor X, the Common Product of the Intrinsic and the Extrinsic Pathway of Blood Coagulation
Authors: Mertens K , Bertina R M
Published: July 2018

The intrinsic activation of human factor X has been studied in a system consisting of purified factors and in plasma. In both these systems factor Xa stimulated the activation of factor X by factor IXa plus factor VIII This is due to the activation of factor VIII by factor Xa. When this factor Xa is formed via the extrinsic pathway, the extrinsic factor X activator functions as a stimulator of the intrinsic factor X activator.
Increased Factor VIII Associated Activities in Cushing's Syndrome: A Probable Hypercoagulable State
Authors: Zanon R Dal Bo , Fornasiero L , Boscaro M , Cappellato G , Fabris F , Girolami A
Published: July 2018

Thirteen women and 2 men affected by Cushing’s syndrome were investigated. The following parameters were used: plasma and urinary cortisol levels, factor VIII assay (antigen, activity and von Willebrand factor) together with other coagulative assays.

Samples were taken before surgery or before medical and/or radiation therapy and every 30–50 days after treatment and continued for 11 months. Cortisol and factor VIII were increased before treatment and decreased slowly after treatment to become normal in 3–4 months. Other clotting tests did not show significant changes. It seems that high plasma cortisol levels may stimulate the production of factor VIII. Patients with Cushing’s syndrome often exhibit thromboembolic complications after surgery. It is likely that the clotting abnormalities responsible for such complications is the increased factor VIII activities level.
Effect of Calcium and Synthetic Peptides on Fibrin Polymerization
Authors: Furlan M , Rupp C , Beck E A , Svendsen L
Published: July 2018

Human fibrinogen was subjected to limited proteolytic attack by thrombin, batroxobin or Agkistrodon contortrix thrombin-like enzyme, yielding desAB-, desA- or desB-fibrin monomers, respectively. Turbidity curves demonstrated that, with all three enzymes, the polymerization process was strongly accelerated by increasing the calcium concentration from 10−5 M to 10−4 M. Synthetic peptide Gly-His-Arg (5 mM), an analogue of the aminoterminal sequence of fibrin β-chain, inhibited aggregation of desB-fibrin monomers at physiological calcium concentration whereas it enhanced aggregation of desA- and desAB-fibrin monomers at calcium concentrations below 10−4 M. On the other hand, Gly-Pro-Arg (1 mM) corresponding to the amino-terminus of fibrin α-chain, dramatically inhibited aggregation of both desA- and desB-fibrins, but it only moderately affected the polymerization of thrombin-induced monomers. We conclude that the observed effects of Gly-Pro-Arg and Gly-His-Arg are not due solely to their competition with fibrin amino-termini for the respective binding sites in the D-domain, but rather reflect conformational changes in fibrin monomers which affect the polymerization process.
DDAVP Stimulates Prostacyclin Production
Authors: Belch J J F , Small M , McKenzie F , Hill P A , Lowe G D O , McIntyre D E , Forbes C D , Prentice C R.M
Published: July 2018

Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGFla, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGFlct by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1α. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1α levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.
Platelet Factor Four and Protamine Sulfate Neutralization of Heparin Fractionated According to Anionic Charge Density
Authors: Poon Man-Chiu , Hurst Robert E , Rives Michael S
Published: July 2018

The role of heparin structure in neutralization by the neutralizing substances (NS) platelet factor 4 (PF4) and protamine sulfate (PS) was investigated using a thrombin clotting assay and a series of more homogeneous heparin fractions varying systematically in charge density (Z). For a given heparin, plotting inverse clotting times measured without NS, and in the presence of PF4 or PS, vs heparin concentration yielded approximately parallel straight lines displaced horizontally according to the amount of NS. Potencies of heparin fractions in the absence of NS, or in the presence of PF4 or PS, depended almost identically upon Z2. Small but significant quantitative differences in potency among equivalent fractions from different heparins showed both PF4 and PS had a slight preference for the least active subfraction of decolorized heparins, but for the most active subfraction of undecolorized heparins. Neutralization of heparin by PF4 and PS probably proceeds by similar mechanisms, but the details of structure outside the antithrombin III-binding oligosaccharide of heparin may enter in differently.
A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver
Authors: Sharoni Yoav , Topal Maria C , Tuttle Patricia R , Berger Henry
Published: July 2018

Of the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.
Problems by Using Whole Blood in Heparin Measurements
Authors: Talstad Ingebrigt
Published: July 2018

Problems by using whole blood (WB) of various packed cell volume (PCV) in heparin measurements were studied. WB had to be used within 1 hr, due to influence of platelet Factor 4. The increase of Ca++ by increasing PCV, had a moderate influence by the assays studied. The recalcification time (RT) of WB was timeconsuming and had low accuracy and precision, due to different heparin response. The activated partial thromboplastin time (APTT) also had low accuracy and precision, due to different heparin response; the results were equal for WB and plasma. The thrombin clotting time (TCT) had high accuracy and precision in plasma. The TCT could also be used for WB since there was a good correlation between T20 (20 NTH U thrombin/ml) using WB, and T30 using plasma (r = 0.89, N = 61). The calcium thrombin clotting time (CaTCT) is not recommended for WB assaying.
Role of Surface Negative Charge in Platelet Function Related to the Hyperreactive State in Estrogen-Treated Prostatic Carcinoma
Authors: Jung Stephanie M , Kinoshita Kenji , Tanoue Kenjiro , Isohisa Ichiro , Yamazaki Hiroh
Published: July 2018

The relationship between platelet surface negative charge and hyperfunction was examined by determining electrophoretic mobility (EPM), aggregability, and sialic acid of platelets in prostatic cancer, prostatic cancer with estrogen, prostatic cancer with estrogen and aspirin, prostatic hypertrophy, and healthy aged males. Estrogen treated prostatic cancer patients had significantly higher platelet EPM. A good linear correlation was found between sialic acid and EPM (r = 0.97, p <0.001). EPM was negatively correlated with primary aggregations by adrenaline and ADP but not with secondary or maximum aggregations, suggesting increased surface negative charge may inhibit primary aggregation. Estrogen and platelet population changes influenced surface negative charge. Neuraminidase removal of platelet surface sialic acid resulted in dose-dependent decreases of EPM which paralleled decreases in sialic acid. Aspirin treated patients and platelets incubated with aspirin in vitro both showed increased platelet EPM. These results suggest that platelet surface negative charge may directly affect platelet function.
An In Vivo Model for Studying Platelet Aggregation and Disaggregation
Authors: Page C P , Paul W , Morley J
Published: July 2018

A simple minimally invasive technique has been developed for the continuous monitoring of 111-Indium labelled homologous platelets in the thoracic (C1) and abdominal (C2) regions of experimental animals. The effects of the aggregatory agents adenosine diphosphate (ADP), collagen and platelet activating factor (PAF) and the anti-aggregatory agent, prostacyclin (PGI2) have been studied in the guinea-pig. Administration of ADP, collagen or PAF produces an increase in counts in C1, a decrease in counts in C2, and hence an increase in the ratio C1/C2. The rise in C1/C2 is more protracted after collagen administration than after ADP or PAF. PGI2 (50-500 ng/kg) reduces the response to ADP. The present technique is both simple, reproducible and although the present experiments are in the presence of heparin, the technique remains functional in the presence of minimal heparin, thus making it a suitable method for studies of platelet function and the evaluation of anti-aggregatory agents in vivo.
Surface Adsorption of Factor XI: II. Evidence that Different Mechanisms Are Involved in Binding to Glass and Plastic Materials
Authors: Mannhalter Christine , Schiffman Sandra
Published: July 2018

Blood coagulation factors XI and XIa possess binding site(s) for glass and plastics, located in the heavy chain of the molecule. To elucidate the nature of binding, adsorption and desorption properties of factor XI and XIa to different surfaces have been studied. Desorption experiments with high salt (2.4 M NaCl) suggest participation of ionic forces in the binding to glass. This is consistent with the decreased adsorption of factor XI (pI – 9.0) to glass with increasing pH. The non-ionic detergent Triton X-100, which splits hydrophobic bonds, desorbs factor XI very well from plastics and partially from glass. The anionic detergent SDS, which will split hydrophobic as well as ionic bonds, is the most effective agent tested for the elution of factor XI from glass. We, therefore infer, that the binding of factor XI to glass is the combined effect of ionic and hydrophobic binding, whereas the adsorption of factor XI to plastics is primarily hydrophobic.
Factor II Related Antigen and Antithrombin III Levels as Indicators of Liver Failure in Consumption Coagulopathy
Authors: Sié P , Letrenne E , Caranobe C , Genestal M , Cathala B , Boneu B
Published: July 2018

In order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and serum demonstrated that the levels of II rAg and of AT III, assessed by the Laurell technique with Behring antisera, were not reduced by the coagulation process. The patients were, a posteriori, classified into two groups according to the absence (group A) or the presence (group B) of factors predisposing to liver failure such as metastasis, cirrhosis, and prolonged shock. II rAg and AT III levels are significantly correlated; they are in the normal range in group A but reduced in group B. Thus II rAg or AT III level determinations are useful markers in the detection of liver failure associated to the consumption phenomenon. These results also suggest that part of the decreased AT III levels reported in severe cases of disseminated intravascular coagulation may be the consequence of an associated liver failure.
Mepacrine Labelling Test and Uranaffin Cytochemical Reaction in Human Megakaryocytes
Authors: Hourdillé P , Fialon P , Belloc F , Boisseau M R , Andrieu J M
Published: July 2018

5-HT storage organelles were observed by electron microscope analysis in human megakaryocytes. They were less numerous per unit of surface than in platelets. Their number depended on the visualization technique employed. Thus after fixation with calcium-enriched glutaraldehyde a higher number of very opaque organelles was observed than of uranaffin-positive organelles after the cytochemical uranaffin reaction. With conventional electron microscopy deep black granules characteristic of dense bodies were not observed.

Fluorescent microscopy showed greenish-yellow granules distributed throughout the whole cytoplasm in 96 ± 1.4% of normal megacaryocytes incubated with mepacrine. In 85.6 ± 5%, 5.28 ± 1.28 granules per 10 ¼m2 were observed.

With the mepacrine labelling test, 74% of the megakaryocytes of a patient with Hermansky-Pudlak syndrome contained no granules. A similar finding was made in the platelets of the same patient. This suggests that mepacrine also stains the dense bodies in the megakaryocytes and that in the Hermansky-Pudlak syndrome the platelet anomaly is secondary to a megakaryocyte anomaly.
Desensitisation in Human and Rabbit Blood Platelets
Authors: Hallam T J , Ruggles P A , Scrutton M C , Wallis R B
Published: July 2018

1. Exposure of human and rabbit blood platelets to all full agonists tested induces agonist-specific (or homologous) desensitisation except in the case of adrenaline and collagen in human platelets.

2. Desensitisation to vasopressin and 5-hydroxytryptamine (5HT) develops rapidly and results from suppression of maximal responsiveness without significant shift in the dose/response curve (Type I). In rabbit platelets, maintenance of desensitisation to 5HT is correlated with the extracellular 5HT concentration. Responsiveness to other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without change in maximal responsiveness.

3. Homologous desensitisation to ADP, U-46619 and thrombin develops more slowly, is correlated with disaggregation and is associated with a shift in the dose/response curve to the right without suppression of maximal responsiveness (Type II). Responsiveness to most other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without a change in maximal responsiveness. However, exposure to thrombin suppresses the maximal response to vasopressin without a shift in the dose/response curve, and exposure to U-46619 causes a shift in the dose/response curve for collagen to the right.

4. In human platelets prolonged exposure to 5HT causes agonist non-specific (or heterologous) desensitisation in which responsiveness to all agonists except adrenaline is suppressed as a result of shifts in the dose/response curves to the right.

5. We propose that Types I and II homologous desensitisation result respectively from prolonged receptor occupancy and from either activation of degradative mechanisms for the agonist or processing of the receptor to a lower affinity state.
In Vivo Platelet Release in Myeloproliferative Disorders
Authors: Ireland H , Lane D A , Wolff S , Foadi M
Published: July 2018

The in vivo platelet release reaction in 22 patients with myeloproliferative disorders has been studied by measuring plasma concentrations of the platelet release product β-throm-boglobulin (βTG). Mean βTG and mean βTG:whole blood platelet count ratio were significantly raised in the patient group taken as a whole compared to an age matched control group. No significant increases were observed in the plasma concentrations of thrombin and plasmin sensitive fibrinogen fragments fibrinopeptide A (FpA) and Bβ1-42. The patients were divided into those who had normal, increased or decreased responses to in vitro ADP-induced platelet aggregation. Mean βTG and the mean βTG:whole blood platelet count ratio were higher in the increased and decreased responders to ADP than in the normal aggregation group, but the differences in means were not statistically significant. Aspirin given to six patients at a dose sufficient to eliminate the secondary phase of ADP-induced platelet aggregation reduced mean βTG and the mean βTG : whole blood platelet count ratio but did not alter mean FpA and Bβ1-42. It is concluded that the enhanced platelet release reaction seen in myeloproliferative disorders is independent of plasma protease activity that arises when coagulation and fibrinolytic systems are activated.
The Role of Factor IX in Tissue Thromboplastin Induced Coagulation
Authors: van den Besselaar A M H P , Ram I E , Alderkamp G H J , Bertina R M
Published: July 2018

Tissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various deficient plasmas were determined as a function of apoprotein concentration, keeping the phospholipid concentration constant. The clotting times of a factor XII-deficient plasma were the same as those of a factor XII/factor IX-deficient plasma, except at very low apoprotein concentrations. However, under those conditions the difference in clotting times was independent of the presence of anti-factor VII serum. Similar observations were made for factor XI-deficient plasma in comparison with factor XI/factor IX-deficient plasma. These results indicate that activation of factor IX by factor VII/tissue thromboplastin does not significantly contribute to plasma coagulation.
Correlation Between Noradrenaline Fluxes, Metabolism and Compartmentalisation in Human Platelets
Authors: Legrand Chantal , Dubernard Véronique , Meyer Philippe
Published: July 2018

(3H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.
Aspirin Ingestion in Primary Thrombocythemia
Authors: Hattori Akira , Sanada Masayoshi , Nagayama Reizo , Shibata Akira , Okuma Minoru
Published: July 2018

Recently Massotti et al. (14) and Patrono et al. (23) have proposed for antithrombotic therapy the use of small single dose of aspirin (ASA) every three or four days in order to inhibit thromboxane A2 production in the platelets but not to inhibit PGI2 production in the endothelium. Their data are theoretical and based on a small number of normal humans. We have examined the effect of a single ingestion of ASA (10 mg/kg) on spontaneous platelet aggregation (SPA) and collagen-induced aggregation (CA) in 11 patients with primary thrombocythemia using the original platelet-rich plasma. SPA and CA were positive in 8 out of 10 and in 11 out of 11 patients respectively before ASA ingestion. ASA abolished both types of aggregation in all patients at 12 h after the ingestion. But the recovery occurred in 1/11 in CA at 24 hr, in about half (3/8 SPA or 7/11 CA) of the patients at 48 hr, in 5/8 (SPA) and 10/11 (CA) at 72 hr and in 7/ 8 (SPA) and 11/11 (CA) at 96 hr. Since SPA and sometimes CA have been considered to be the parameters of the effect of ASA on hyperreactivity of the platelets in vivo, resulting in arterial thrombosis or insufficiency in these patients, our results suggest that daily or at least once per two days ingestion of ASA may be necessary in these patients. These results were discussed in relation to the platelet survivals (6.5â€“10 days) and the platelet cyclo-oxygenase or lipoxygenase activities (deficient in 3 patients for the former and in 2 for the latter) in our patients.
Factor IX Thrombogenicity: In Vivo Effects on Coagulation Activation and a Case Report of Disseminated Intravascular Coagulation
Authors: Small M , Lowe G D O , Douglas J T , Forbes C D , Prentice C R M
Published: July 2018

An episode of defibrination with bleeding following high dose Edinburgh Factor IX (D.E.F.IX) replacement in a patient with haemophilia B undergoing knee joint replacement is reported. We have also monitored plasma fibrinopeptide A levels in patients with haemophilia B following ten standard doses of D.E.F.IX (15–20 u/kg) and have been unable to document any change. Activation of the coagulation system, as previously noted, appears to be related to the use of Factor IX concentrates in high doses.
Assessment of Antithrombotic Properties of Sodium Ibuprofen
Authors: Esquivel Carlos O , Bergqvist David , Björck Claes-Göran , Carson Stan N , Nilsson Bodil
Published: July 2018

The effect of sodium ibuprofen on platelet activity in vivo and the lysability of ex vivo thrombi was investigated. The formation of a hemostatic platelet plug in the rabbit mesentery and platelet embolism as a response to a laser-induced injury in the ear chamber of rabbits were used as models for determining platelet activity. Ibuprofen at a dose of 25 mg/kg i.v. was found to increase the primary (PHT) and the total hemostatic plug formation time (THT). The same dose decreased the number of cumulative emboli over a 10 min period after a laser injury to arterioles. A dose of 10 mg/kg i.v. did not affect the formation of the hemostatic platelet plug. In dogs, doses of 10, 25 und 50 mg/kg did not enhance the release of 125I-FDP from the thrombi after incubation in plasmin, but the largest dose which is approximately five times the recommended dose in humans, did significantly decrease the thrombus weight 90 and 180 min after the drug administration. In conclusion, sodium ibuprofen was shown to have an inhibitory effect on platelet function in vivo and in large doses was also found to diminish the thrombus weight.
Prostaglandin Synthesis in Aorta and Platelets of Fawn-Hooded Rats with Platelet Storage Pool Disease and Its Response to Cholesterol Feeding
Authors: Wey H , Gallon L , Subbiah M T R
Published: July 2018

Fawn-hooded (FH) rats possess a hereditary bleeding diathesis and platelet function defect, which is presumably the result of a storage pool deficiency. In this study, we have investigated the prostaglandin synthesis capacity of platelets and aorta from FH rats as compared to Sprague Dawley (SD) rats, after 2 months on a normal or 1% cholesterol diet. No difference was found in thromboxane B2 (TXB2) production by platelets of FH as compared to SD rats. Cholesterol-feeding resulted in an increased TXB2 production by SD platelets, but not FH platelets. FH rat aorta was found to convert significantly less arachidonic acid (AA) to 6-keto-prostaglandin-F1α (PGF1α) and cholesterol-feeding stimulated this reduced capacity. In contrast, cholesterolfeeding in the SD rat reduced aortic 6-keto-PGF1α production. Aggregation of platelet-rich plasma by AA was enhanced in the cholesterol-fed FH rat. This result suggests the possibility of an influence of platelet aggregability on aortic prostacyclin production.
Effect of Aspirin on Platelet 5-Hydroxytryptamine and Beta-Thromboglobulin Plasma Levels in Patients with Myeloproliferative Diseases
Authors: Viero P , Cortelazzo S , Bassan R , Barbui T
Published: July 2018

14 patients with myeloproliferative diseases (MD) showed low 5-hydroxytryptamine (5-HT) platelet content and high beta-thromboglobulin (β-TG) plasma levels.

This pattern could support the view that MD platelets undergo “in vivo“ degranulation.

A single dose of aspirin was unable to induce modification of platelet 5-HT and plasma β-TG, whereas 6 out of 14 patients

No modification of platelet 5-HT was obtained suggesting that the cause of dense bodies deficiency may lie in the production of abnormal platelets and not be related to “in vivo” degranulation.
Effects of Ticlopidine on Platelet Function and Blood Coagulation
Authors: Violi F , Alessandri C , Frattaroli S , Ghiselli A , Balsano F
Published: July 2018

A double blind study was performed on 20 atherosclerotic patients. A placebo was administered to one group of 10 patients (group A) and ticlopidine (500 mg/day) was administered to another group of 10 patients (group B) for one month. ADP and collagen-induced platelet aggregation (PA), platelet malondial-deyde (MDA) produced by thrombin stimulation and plasma beta-thromboglobulin (βTG) levels, prothrombin time, activated partial thromboplastin time (APTT) fibrinogen, antithrombin (AT) III, fibrin(ogen) degradation products, alpha2-antiplasmin and plasminogen were evaluated in both groups before and after treatment. No changes in PA, MDA and βTG were seen in group A. Group B showed a significant decrease of PA, βTG and a significant increase of MDA. No changes on blood coagulation data were seen in either group. This study suggests that ticlopidine is able to inhibit platelet function in vivo.
Surface Labeling of Human Platelets by Reductive Methylation
Authors: Spycher Martin O , Clemetson Kenneth J , Lüscher Ernst F
Published: July 2018

A simple, reproducible method for the specific labeling of the surface proteins of human platelets with tritium is described. The labeled platelets were analyzed by two-dimensional gel electrophoresis (isoelectric focusing/sodium dodecyl sulfate-poly-acrylamide gel electrophoresis) followed by fluorography and the results compared with those obtained by conventional methods. Reductive methylation gave an intense labeling of membrane glycoproteins. There was no cross-linking of the labeled membrane proteins by formaldehyde nor could clear evidence be found that inner proteins were labeled by permeation of the reagents through the plasma membrane. As well as previously described platelet membrane glycoproteins, several others could be detected that were not invariably seen using labeling techniques.
Characterization of Factor VIII Related Protein Synthesized by Human Endothelial Cell: A Study of Structure and Function
Authors: Chan Vivian , Chan T K
Published: July 2018

Crossed immunoelectrophoresis showed that factor VIII related protein (VIII R) synthesized in the human endothelial cell (EC-VIII R) had faster electrophoretic mobility than that secreted into the culture medium (MED-VIII R). Sodium dodecyl sulphate agarose gel electrophoresis followed by radioimmunofixation showed that EC-VIII R consisted of molecules varying from 0.26 × 106 to 3.76 × 106 daltons while MED-VIII R had molecules ranging from 0.93 × 106 to greater than 10 × 106 daltons, similar to that present in plasma. The smallest VIII R molecule present in normal plasma or spent culture medium (0.93 × 106 daltons) corresponded to a tetramer of subunits of 0.22-0.24 × 106 daltons. Only molecular forms greater than 3.76 × 106 daltons possessed ristocetin cofactor activity. Sonication (15 μ. amplitued for 30 secs) effectively broke the non-covalent bonds of the VIII R multimers resulting in smaller molecules. Thus endothelial cells in culture synthesized VIII R subunits and assembled them into the higher multimeric forms on secretion. Different types of von Willebrand disease could result from defects of either of the two processes.
Sequential Treatment of Arterial Occlusions with Porcine Plasmin and Low Dose Streptokinase
Authors: Marbet G A , Eichlisberger R , Duckert F , da Silva M A , Biland L , Widmer L K , Ritz R , Schmitt H E
Published: July 2018

Sequential treatment of arterial occlusions of the leg with porcine plasmin and low dose streptokinase results in a strong systemic proteolysis as already seen in deep leg vein thrombosis. In 31 of 45 patients the blood flow through major arterial segments could be restored. Thrombolytic success is possible within the first two treatment days but for the majority of the cases fibrinolytic therapy for 3-6 days is needed. On the average treatment was 1 day shorter than in DVT cases. No statistical relationship between local thrombolysis and systemic proteolysis was detected.

The thrombolytic efficacy of this regimen compares favourably with earlier experience on fibrinolytic therapy in arterial occlusions.
Exercise-Induced Fibrinolysis – Fact or Fiction?
Authors: Marsh N A , Gaffney P J
Published: July 2018

The effect of strenuous exercise on the fibrinolytic and coagulation mechanisms was examined in six healthy male subjects. Five min bicycle exercise at a work-rate of 800 to 1200 kpm. min−1 produced an abrupt increase in plasma plasminogen activator levels which disappeared after 90 min. However, there was no change in early or late fibrin degradation products nor was there a change in fibrinopeptide A levels or βthromboglobulin levels after exercise although activated partial thromboplastin times were significantly shortened. It is concluded that strenuous exercise does not produce any real increase in fibrinogen-fibrin conversion nor any real increase in the breakdown of these proteins. The role of exercise-induced release of plasminogen activator remains unclear, but probably helps to maintain plasma levels in a discontinuous manner concurrently with the continuous low-level secretion from the vascular wall. The shortening of partial thromboplastin time may be due to the raised levels of plasminogen activator changing the activation state of other coagulation factors.
Partial Primary Structure of Human α2-Antiplasmin – Homology with Other Plasma Protease Inhibitors
Authors: Lijnen H R , Wiman B , Collen D
Published: July 2018

Human α2-antiplasmin was digested with trypsin and with chymotrypsin and about 70 percent of the amino acids were sequenced and aligned in peptides ranging from 2 to 33 residues. Here we report five sequences of 21 to 33 residues. When these were compared with the primary structures of antithrombin III, α1-antitrypsin and ovalbumin, which belong to the same protein superfamily (Hunt and Dayhoff [1980] Biochem Biophys Res Commun 95: 864–871), three peptides showed clear homologies with these proteins, indicating that α2-antiplasmin also belongs to that superfamily. In addition, α2-antiplasmin appeared to contain at least one internal homology.
Intravenous Injections of Tissue Thromboplastin and Phospholipase C in Sheep
Authors: Carlsen E , Hetland Ø , Janson T L
Published: July 2018

To gain further information about the protective effect of phospholipase C (PLC) against intravascular coagulation, we have carried out studies in sheep. Thromboplastin infusions gave a dose-dependent increase in pulmonary platelet-bound 11 inactivity and a dose-dependent decrease in arterial oxygen tension, factor VIIIc activity, fibrinogen level and platelet count. All these parameters were significantly correlated when doses of 0.4 – 0.5 ml bovine thromboplastin/kg/min were given. The model therefore seemed suitable for testing the effect of PLC in preventing intravascular coagulation elicited by infusion of thromboplastin. Our experiments show that PLC may have a certain protective effect against pulmonary microembolism caused by thromboplastin infusion, but there was no normalization of the pulmonary 111In-radioactivity from labelled platelets, arterial oxygen tension, coagulation factors or platelet count in contrast to earlier observations in rats. Protection was observed against the effect of lethal doses of thromboplastin, but although small doses of PLC were used, both sheep eventually died of PLC toxicity.
Thrombin-Induced Platelet Malondialdehyde (MDA) Formation in Normal Subjects and in Women Taking Oral Contraceptives
Authors: Hellstern P , Miyashita C , Köhler M , Wenzel E , Holl W
Published: July 2018

Thrombin-induced platelet malondialdehyde (MDA) production and platelet count were studied in 82 male and 74 female healthy blood donors. 37 women on oral contraceptives (OC) had significantly lower values of MDA production than women who were not using the pill. There were no statistically significant differences of MDA production in women on a low dose estrogen, a medium dose, and a relatively high dose. Males had significantly higher values than females. In 15 further subjects (5 males, 5 OC-users, 5 OC-nonusers) the kinetics of MDA formation was determined by using increasing doses of thrombin. No significant differences could be found. Platelet count in women on OCs was lightly increased, but the difference was not significant.
Studies on the Action of Ethamsylate (Dicynene) on Haemostasis
Authors: Hutton R A , Wickham E A , Reed J V , Tuddenham E G D
Published: July 2018

Twelve healthy subjects received ethamsylate or a placebo by mouth over a 48 h period in a randomized double-blind trial. The template bleeding time (including estimation of amount of blood loss), platelet aggregation studies, and plasma levels of plasminogen, alpha2-antiplasmin and fibronectin were carried out before and during treatment. The effect of a single dose (600 mg) of aspirin, given 24 h after commencement of treatment, was also determined.

Neither ethamsylate nor placebo caused a significant change in the basal values of any of the variables monitored but both the prolongation of the bleeding time and the amount of blood loss induced by aspirin were significantly less during ethamsylate treatment than with placebo. Ethamsylate failed to prevent the aspirin-induced elimination of the secondary wave of platelet aggregation.

We conclude that ethamsylate may reduce the haemorrhagic symptoms associated with mild functional platelet defects.
Inhibition of PAF-lnduced Systemic Responses in the Rat, Guinea Pig, Dog and Primate by the Receptor Antagonist SRI 63-441
Authors: Handley D A , Tomesch J C , Saunders R N
Published: July 2018

Systemic administration of synthetic PAF produces a number of dose-dependent circulatory effects in a variety of species. We have evaluated a novel PAF antagonist, SRI 63-441, for its ability to inhibit PAF-induced effects in the rat, guinea pig, dog and primate. In the rat, a 100 ng kg-1 i.v. PAF challenge produced a (mean ± 1 S.D.) 39 ± 5% decrease in carotid blood pressure. Prior injection of SRI 63-441 inhibited this hypotensive response in a dose-dependent manner, with an ED50 of 0.15 mg kg-1 i.v. In the guinea pig, PAF at 100 ng kg-1 elicited a 50 ± 8% increase in hematocrit and a 50 ± 11% elevation in bronchial resistance. The ED50 values for inhibition by SRI 63-441 of these two physiological parameters were 0.012 mg kg-1 and 0.035 mg kg-1 i.a., respectively. Dogs challenged with 1.5 μg kg-1 PAF i.v. exhibited 28.7 ±6.5% increase in hematocrit 10 min after injection. The ED50 value for SRI 63-441 inhibition of hemoconcentration in the dog was 0.18 mg kg-1 i.v. In the primate model of PAF-induced hemoconcentration, controls responded to 3.5 pg kg-1 i.v. PAF with a 30 ± 6% increase in hematocrit. Using the primates in a cross-over design, the ED50 OF SRI 63-441 WAS 0.11 MG KG 1 i.v. At this ED50 value, the ratio of nmol kg-1 PAF used versus nmol kg-1 antagonist is ∼1:25. The effectiveness of SRI 63-441 in these models suggest potential clinical applications in disease states involving hyperpermeability and pulmonary dysfunction.
Der Einfluss des Body Mass Index auf die Mobilisation von Patienten in der Frührehabilitation
Authors: Liebl Max , Schwedtke Christine , Schröder Isabelle , Elmer Nancy , Reißhauer Anett
Published: July 2018

Hintergrund Die Mobilisierung stellt in der Frührehabilitation adipöser Patienten eine zentrale Aufgabe und gleichzeitig eine besondere Herausforderung dar. Insbesondere bei höhergradiger Adipositas ist ein erhöhter Personal- und Materialaufwand notwendig. In der vorliegenden Arbeit soll der Zusammenhang zwischen Body Mass Index und der Entwicklung der mobilitätsbezogenen Funktionsfähigkeit untersucht werden.

Material und Methoden Diese retrospektive Kohortenstudie wurde an einer Stichprobe von n=129 initial immobilen Patienten in der fachübergreifenden Frührehabilitation (FR) an einer Universitätsklinik durchgeführt. Hauptzielkriterium war der Mobilisierungsfortschritt der Patienten. Die Mobilität wurde mittels Charité Mobilitäts-Index erfasst (CHARMI®, eine Mobilitäts-Rangskala von 0 bis 10 Punkten). Die Mobilisierungsfortschritte (CHARMI®-Werte pro Behandlungstag) wurden nach BMI-Gruppen verglichen.

Ergebnisse Die Gruppen der Normalgewichtigen (0,13 CHARMI-Punkte/Tag) und der Untergewichtigen (0,13) zeigten eine schnellere Mobilisierung als die Gruppen der Übergewichtigen (0,11) und der Adipösen (0,09). Adipöse Patienten erreichen am Ende der Frührehabilitation zwar annähernd das gleiche Mobilisationsniveau wie Patienten ohne Übergewicht, benötigen hierfür jedoch im Median 9 Tage länger (29 statt 20) als Normalgewichtige.

Diskussion Die Verteilung der Werte zeigt eine lineare Assoziation zwischen einem erhöhten BMI und geringeren Mobilisierungsfortschritten. Diese beschriebene Assoziation besteht trotz maximaler Therapiedichte und Mehraufwand für stark adipöse Patienten in der durchgeführten Frührehabilitation. Klinisch lässt sich daraus folgern, dass durch eine Maximalversorgung auch bei schwer adipösen Patienten eine Mobilisierung erzielt werden kann, die annähernd der von normalgewichtigen Patienten entspricht. Dieser Zustand kann jedoch nur mit einem deutlichen Mehraufwand an Personal, Material und Zeit erreicht werden.
Endoskopische Mukosaresektion (EMR) – Schritt für Schritt
Authors: Pagitz Manuel , Koch Maria , Hausmann Johannes , Albert Jörg
Published: July 2018

Colonoscopy with polypectomy has been shown to reduce the risk of colon cancer development. It is considered a fundamental skill for all endoscopists who perform colonoscopy. A variety of polypectomy techniques and devices are available, and their use can vary greatly based on local availability and preferences. Polyps that are difficult to remove due to location or size require advanced resection techniques, such as endoscopic mucosal resection (EMR) and the use of special devices for safe and effective removal. However, colonic EMR is not routinely part of the standard endoscopic curriculum that is normally offered to gastroenterologists. It requires dedicated training in advanced endoscopic resection techniques, clinical and interpretive skills, and the knowledge and ability to manage complications.

The two most common post-polypectomy complications are bleeding and perforation. Their frequency can be limited with the use of meticulous polypectomy techniques and the application of some prophylactic manoeuvres.

This paper gives a review of the step by step technique of polypectomy and its complications from the perspective of the practicing gastroenterologist.
Skoliosespezifische Physiotherapie bei Patienten mit idiopathischer Adoleszentenskoliose (AIS) – ein narratives Review
Authors: Nisser Jenny , Smolenski Ulrich , Śliwiński Grzegorz , Krüger Paula , Heinke Andreas , Malberg Hagen , Werner Michael , Drossel Welf-Guntram , Śliwiński Zbigniew , Derlien Steffen
Published: July 2018

Fragestellung Die Arbeit soll einen aktuellen Überblick über die konservativen Therapieverfahren (skoliosespezifischen Physiotherapie) bei Patienten mit idiopathischer Adoleszentenskoliose (AIS) im Allgemeinen liefern. Im Speziellen ist die FED-Methode (Fixation, Elongation, Derotation), welche Inhalt eines Forschungsprojektes (Förderkennzeichen: 19200 BR/3) ist, Gegenstand der Recherche.

Material und Methoden Diese narrative Literaturrecherche wurde in den Zeitraum von Nov. 2016 bis Jul. 2017 durchgeführt. Die erste Recherche erzielt die Auflistung der Therapieverfahren für Skoliosepatienten, während der zweite Teil der Charakterisierung dieser Verfahren dient. Ergebnisse Insgesamt wurden 34 relevante Literaturstellen identifiziert und der Volltextanalyse unterzogen. Es existieren Behandlungsverfahren mit und ohne Autokorrektur. Zu den Behandlungsverfahren mit Autokorrektur zählen die folgenden Konzepte: Schroth-Methode, Side Shift Program, SEAS-Program, DoboMed, Lyon School, BSPTS, FITS und teilweise Klapp’sches Kriechen. Die Verfahren Vojta-Therapie, PEP-Programm, Hanke-Konzept E-Technik®, Bobath-Konzept, PNF und Riemenübungen gehören zu den Behandlungsverfahren ohne Autokorrektur.

Diskussion Die Schroth-Methode ist ein grundlegendes Therapieverfahren, woraus sich weitere Verfahren ableiteten. Zur Charakterisierung der FED-Methode (Fixation, Elongation, Derotation) wurde keine Referenz gefunden. Dieses Behandlungsverfahren wurde lediglich kurz in einer Arbeit erwähnt.

Schlussfolgerung Verschiedene Verfahren werden bei AIS angewendet. Diese Arbeit bietet einen Überblick über diese Therapieverfahren. Weitere Untersuchungen sollten sich mit den Wirkmechanismen der die FED-Methode befassen.
Influence of stripline coupling on the magnetostatic mode line width of an yttrium-iron-garnet sphere
Authors: Yang Y. , Harder M. , Rao J. W. , Yao B. M. , Lu W. , Gui Y. S. , Hu C.-M.
Published: July 2018

We study the effect of stripline coupling on the damping of magnetostatic modes in an yttrium-iron-garnet sphere. Both the magnetostatic dispersion and line width display a pronounced dependence on the YIG-stripline separation, with the coupling dominating the line width for small separations. By suppressing the coupling effect we use a broadband technique to measure both the Gilbert damping, α = (6.5 ± 0.5) × 10−5, and the inhomogeneous broadening which is mode dependent and as small as 0.075 MHz. Our study therefore reveals the importance of, and a method for, exploring the influence of coupling on damping, which may be useful for future device characterization and design.
Necessary conditions for extended noncontextuality in general sets of random variables
Authors: Amaral Barbara , Duarte Cristhiano , Oliveira Roberto I.
Published: July 2018

In this paper, we explore the graph approach to contextuality to restate the extended definition of noncontextuality as given by Kujala et al. [Phys. Rev. Lett. 115, 150401 (2015)] using graph-theoretical terms. This extended definition avoids the assumption of the pre-sheaf or non-disturbance condition, which states that if two contexts overlap, then the marginal distribution obtained for the intersection must be the same, a restriction that will never be perfectly satisfied in real experiments. With this, we are able to derive necessary conditions for extended noncontextuality for any set of random variables based on the geometrical aspects of the graph approach, which can be tested directly with experimental data in any contextuality experiment and which reduce to traditional necessary conditions for noncontextuality if the non-disturbance condition is satisfied.
Quadrupolar mode measurements for space charge dominated beams
Authors: Stem William D. , Beaudoin Brian L. , Haber Irving , Koeth Timothy W.
Published: July 2018

On-line monitoring of beam quality requires non-invasive transverse phase space diagnostics. Emittance measurement is particularly challenging for high-intensity particle beams since space charge complicates the beam dynamics during measurement. Quadrupolar mode measurements have been empirically shown to provide information about the beam emittance, but so far only for small relative space charge effects, where the results depend on a linear theory. We present a quadrupolar mode measurement for space charge dominated beams with unsplit tunes using multi-turn resonant excitation. Results from experiments performed at the University of Maryland Electron Ring are compared to both analytic and numerical analysis of the rms envelope equations.
Study on the maximum stable output of a novel s-band micro-pulse electron gun
Authors: Yang Deyu , Li Boting , Zhao Jifei , Zhou Kui , Yang Ziqin , Tan Weiwei , Yang Yujia , Lu Xiangyang
Published: July 2018

A novel S-Band Micro-Pulse electron Gun (MPG) which works at the left crossover point energy EcI on the Secondary Electron Yield (SEY) curve was proposed. The working principles of the MPG were presented. The maximum output beam current limited by space charge effects and beam loading effects was investigated by theoretical analysis. The result shows that the maximum beam current is decided by the parameters of the MPG such as resonant frequency, cavity length, shunt impedance and the secondary emission property of the cathode and grid, having nothing to do with the power flowed into the cavity. The low shunt impedance and the low slope of the SEY curve can help increasing the maximum beam current. According to the principles, a MPG with the frequency of 2.856 GHz has been designed and constructed. The steady working state was achieved by using oxygen free copper and molybdenum grid with different transmission coefficient. It was found a good agreement between the analysis and the experiments.