bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and mechanism of a highly efficient and stable Z-scheme Ag3PO4/reduced graphene oxide/Bi2MoO6 visible-light photocatalyst
Authors: Zhu Pengfei , Chen Yanjun , Duan Ming , Ren Zhihao , Hu Min
Published: June 2018

A novel Ag3PO4/reduced graphene oxide/Bi2MoO6 (Ag3PO4/RGO/Bi2MoO6) Z-scheme photocatalyst has been successfully prepared by a precipitation-solvothermal method.
Electromagnetic interference (EMI) shielding performance of lightweight metal decorated carbon nanostructures dispersed in flexible polyvinylidene fluoride films
Authors: Rengaswamy Kumaran , Sakthivel Dinesh Kumar , Muthukaruppan Alagar , Natesan Balasubramanian , Venkatachalam Subramanian , Kannaiyan Dinakaran
Published: June 2018

This work demonstrates the enhanced EMI shielding performance of metal/carbon nanomaterials incorporated in a PVDF matrix with better electrical properties.
Red phosphorus in its two-dimensional limit: novel clathrates with varying band gaps and superior chemical stabilities
Authors: Zhu Zhili , Cui Ping , Cai Xiaolin , Xia Mengjiao , Jia Yu , Zhang Shengbai , Zhang Zhenyu
Published: June 2018

First-principles calculations within density functional theory reveal the preferred structures of red phosphorus in the two-dimensional (2D) limit to be porous with intriguing structural, electronic, and chemical properties.
Porous CaFe2O4 as a promising lithium ion battery anode: a trade-off between high capacity and long-term stability
Authors: Han Chunhua , Zhang Xiao , Xu Xiaoming , Li Qi , He Qiu , Meng Jiashen , Wang Xuanpeng , Liu Ziang , Wu Peijie , Mai Liqiang
Published: June 2018

The porous CaFe2O4 was synthesized by a facile sol–gel method and shows a distinct trade-off in terms of high capacity and long-term stability compared to pristine iron oxides.
Direct growth of CuCo2S4 nanosheets on carbon fiber textile with enhanced electrochemical pseudocapacitive properties and electrocatalytic properties towards glucose oxidation
Authors: Xu Weina , Lu Junlin , Huo Wangchen , Li Jien , Wang Xue , Zhang Cuiling , Gu Xiao , Hu Chenguo
Published: June 2018

CuCo2S4 nanosheets on carbon fiber textile were synthesized by a one-step hydrothermal procedure for high-performance supercapacitors and non-enzymatic glucose sensors.
Cu/Ni nanoparticles supported on TiO2(B) nanotubes as hydrogen generation photocatalysts via hydrolysis of ammonia borane
Authors: Wang Chenyang , Sun Dongdong , Yu Xiaofei , Zhang Xinghua , Lu Zunming , Wang Xixin , Zhao Jianling , Li Lanlan , Yang Xiaojing
Published: June 2018

Cu0.64Ni0.36-TiO2(B) NTs with a lower bandgap energy show a high H2 generation rate in the hydrolysis of AB.
Nanofluidic transport through humic acid modified graphene oxide nanochannels
Authors: Konch Tukhar Jyoti , Gogoi Raj Kumar , Gogoi Abhijit , Saha Kundan , Deka Jumi , Reddy K. Anki , Raidongia Kalyan
Published: June 2018

The chemical similarity of graphene oxide (GO) and humic acid has been exploited to fine-tune the ionic and molecular transport properties of a lamellar GO membrane.
Hydroxy-assisted regio- and stereoselective synthesis of functionalized alkenes via phosphine-catalyzed β′-umpolung addition of o-hydroxy aromatic aldimines to allenoates
Authors: Cheng Kunpeng , Bao Yishu , Wang Jiahua , Dai Zonghao , Lu Jinrong , Zhou Qingfa
Published: June 2018

An unprecedented β′-umpolung addition of o-hydroxy aromatic aldimines with allenoates has been developed under the catalysis of phosphine.
Phosphinoyl-functionalization of unactivated alkenes through phosphinoyl radical-triggered distal functional group migration
Authors: Chen Dong , Wu Zhen , Yao Yingming , Zhu Chen
Published: June 2018

Reported herein is a novel, mild, and practical protocol for the radical-mediated phosphinoyl-functionalization of unactivated alkenes through distal functional group migration.
Fabrication of EPYR/GNP/MWCNT carbon-based composite materials for promoted epoxy coating performance
Authors: Hussein Mahmoud A. , Abu-Zied Bahaa M. , Asiri Abdullah M.
Published: June 2018

Composite materials containing epoxy resin and reinforced by mixed carbon-based nano-fillers (GNP/MWCNT) have been fabricated using the dissolution casting technique with the help of ultrasonic assistance for promoted epoxy coating performance.
Fabrication of nitrogen-doped ZnO nanorod arrays by hydrothermal synthesis and ambient annealing
Authors: Kobayashi Ryosuke , Kishi Tetsuo , Katayanagi Yuta , Yano Tetsuji , Matsushita Nobuhiro
Published: June 2018

Nitrogen-doped ZnO nanorod arrays were fabricated by hydrothermal synthesis using a zinc–ammine complex solution, followed by annealing under ambient conditions.
Development, characterization and application of hydroxypropylmethylcellulose films enriched with cypress seed extract
Authors: Rhimi Wafa , Boulila Abdennacer , Gheribi Rim , Khwaldia Khaoula
Published: June 2018

Biodegradable films made from hydroxypropylmethylcellulose and incorporating cypress seed extract were developed and showed good functional properties for active packaging applications.
Kinetically controlled synthesis of bimetallic nanostructures by flowrate manipulation in a continuous flow droplet reactor
Authors: Santana Joshua S. , Koczkur Kallum M. , Skrabalak Sara E.
Published: June 2018

We show that different Au–Pd nanoparticles, ranging from sharp-branched octopods to core@shell octahedra, can be achieved by inline manipulation of reagent flowrates in a microreactor for seeded growth.
Flexible and non-volatile redox active quasi-solid state ionic liquid based electrolytes for thermal energy harvesting
Authors: Taheri Abuzar , MacFarlane Douglas R. , Pozo-Gonzalo Cristina , Pringle Jennifer M.
Published: June 2018

Towards the development of stable thermocells for harvesting low-grade waste heat, non-volatile and flexible electrolyte films are reported.
Substantially enhanced front illumination photocurrent in porous SnO2 nanorods/networked BiVO4 heterojunction photoanodes
Authors: Bhat Swetha S. M. , Suh Jun Min , Choi Seokhoon , Hong Seung-Pyo , Lee Sol A. , Kim Changyeon , Moon Cheon Woo , Lee Mi Gyoung , Jang Ho Won
Published: June 2018

The porous SnO2 nanorods/networked BiVO4 heterojunction is identified as apromising photoanode which exhibits high photocurrent under front illumination.The interplay of porous SnO2 NRs and optimum coverage of BiVO4 lead to high PEC performance.
A nitrogen-doped 3D open-structured graphite nanofiber matrix for high-performance supercapacitors
Authors: Zhou Yongsheng , Zhu Yingchun , Xue Dongfeng , Xu Bingshe
Published: June 2018

An N-doped 3D ordered mesoporous graphite nanofiber (3D OMGNF-N) with an N-doping level of up to 16.5 at% for high-performance supercapacitors is designed and synthesized.
Room temperature colloidal synthesis of CsPbBr3 nanowires with tunable length, width and composition
Authors: Liu Yi , Guo Mingrui , Dong Shun , Jiao Xiuling , Wang Ting , Chen Dairong
Published: June 2018

We developed a room temperature ligand-assisted colloidal method to synthesize single-crystalline CsPbBr3 nanowires (NWs) directly from precursor powders.
Correction: Gate-tunable interfacial properties of in-plane ML MX2 1T′–2H heterojunctions
Authors: Liu Shiqi , Li Jingzhen , Shi Bowen , Zhang Xiuying , Pan Yuanyuan , Ye Meng , Quhe Ruge , Wang Yangyang , Zhang Han , Yan Jiahuan , Xu Linqiang , Guo Ying , Pan Feng , Lu Jing
Published: June 2018

Correction for ‘Gate-tunable interfacial properties of in-plane ML MX2 1T′–2H heterojunctions’ by Shiqi Liu et al., J. Mater. Chem. C, 2018, DOI: 10.1039/c8tc01106k.
Cirrhosis regression: extrahepatic angiogenesis and liver hyperarterialization persist
Authors: Payancé Audrey , Rautou Pierre-Emmanuel
Published: June 2018

Data on the consequences of cirrhosis regression on portal hypertension and on splanchnic and systemic hemodynamic are scarce. Previous studies have reported a decrease in hepatic venous pressure gradient following antiviral treatment in patients with hepatitis B or C related cirrhosis. However, these studies did not investigate splanchnic and systemic hemodynamic changes associated with virus control. To fill this gap in knowledge, in a recent issue of Clinical Science, Hsu et al. (vol. 132, issue 6, 669-683) used rat models of cirrhosis induced by thioacetamide and by bile duct ligation and provided a comprehensive analysis of the effects of cirrhosis regression on splanchnic and systemic hemodynamics. They observed a significant reduction in portal pressure accompanied by a normalization of systemic hemodynamic (normal cardiac index and systemic vascular resistance) and a decrease in intrahepatic vascular resistance. No change in extrahepatic vascular structures were observed despite normalization of collateral shunting, meaning that portosystemic collaterals persist but are not perfused. One intriguing part of their results is the only marginal effect of cirrhosis regression on liver hyperarterialisation. This result suggests that changes in splanchnic hemodynamic features induced by cirrhosis remain when hepatic vascular resistance decreases, raising the hypothesis of an autonomous mechanism persisting despite regression of intrahepatic vascular resistance. Microbiota changes and bacterial translocation might account for this effect. In conclusion cirrhosis regression normalizes systemic hemodynamics, but some splanchnic hemodynamic changes persist including extrahepatic angiogenesis and liver hyperarterialization.
Verzögerte Kohlenmonoxidenzephalopathie
Authors: Lettow Iris , Hoffmann Anna , Burmeister Hartmut Peter , Toepper Rudolf
Published: June 2018

Kohlenmonoxid-Vergiftungen sind weltweit häufige Intoxikationen, bei denen das Spektrum der Symptome von leichten Kopfschmerzen und Schwindel bis hin zum Tod reicht. Wenig bekannt ist die verzögerte Kohlenmonoxidenzephalopathie, die mit einer Latenz von 2–40 Tagen nach dem Initialereignis auftreten kann. Häufige klinische Manifestationen sind dabei Bewegungsstörungen, kognitive- oder affektive Störungen. Dieser Artikel beschreibt exemplarisch den Fall eines Patienten mit einer akzidentellen Kohlenmonoxidvergiftung mit verzögert auftretender Enzephalopathie. In der anschließenden Übersichtsarbeit wird die Literatur hinsichtlich Klinik, Diagnostik, Pathophysiologie und Therapieoptionen zusammengefasst.
„Niemanden zurücklassen“ – migrierte Menschen in der Drogen- und Suchthilfe
Authors: Leicht Astrid , Köhnlein Ralf
Published: June 2018

Die EU-Binnenmigration und die Fluchtbewegungen der letzten Jahre stellen die deutsche Gesellschaft und Politik mit ihren Integrations- und Krisenbewältigungskompetenzen auf die Probe und gehen auch an der Drogen- und Suchthilfe und -prävention nicht spurlos vorüber.

Straßensozialarbeit und niedrigschwellige Kontakt- und Beratungsstellen sind häufig die ersten und oft die einzigen Suchthilfe-Angebote, die migrierte Menschen, die Probleme mit psychoaktiven Substanzen haben, in ihrer Vielfalt, ihrer Individualität und gleichzeitig der Komplexität ihrer Problemlagen wahrnehmen und in Kontakt kommen.

Fixpunkt ist ein Berliner Träger, der hauptsächlich niedrigschwellige Suchthilfe- und Infektionsschutz-Angebote realisiert und sich als einer der ersten Träger der Suchthilfe neuen Herausforderungen und bekannten Herausforderungen stellte.
Bedeutung und Probleme bei der Anwendung des Gendiagnostikgesetzes im klinischen Alltag
Authors: Daunderer Johannes , Ebermann Thorsten , Beckmann Britt-Maria
Published: June 2018

Seit Februar 2010 ist das Gendiagnostikgesetz in Kraft getreten. Das grundsätzlich begrüßenswerte Gesetz bereitet jedoch bei gesetzeskonformer Umsetzung im klinischen Alltag zum Teil erhebliche Probleme. Einige dieser Schwierigkeiten sollen im Folgenden angesprochen werden.
Genetik der koronaren Herzkrankheit
Authors: Wolf Bernhard , Kessler Thorsten , Schunkert Heribert
Published: June 2018

Die Atherosklerose mit ihren Folgeerkrankungen, der koronaren Herzkrankheit (KHK/MI) und der zerebralen arteriellen Verschlusskrankheit (cAVK/Schlaganfall), gilt weltweit als führende Todesursache. Schon lange sind sich die Forscher über die herausragende Rolle der Vererbung bei der Entstehung der Atherosklerose im Klaren, doch erst im vergangenen Jahrzehnt legten molekulargenetische und epidemiologische Methoden die Vererbungsstruktur der Erkrankung offen. Genomweite Assoziationsstudien konnten bisher über 160 Loci genomweit signifikant mit der KHK assoziieren. Funktionelle Analysen helfen bei der Entschlüsselung zugrunde liegender Mechanismen und sollen den Grundstein für die Entwicklung neuer Therapiestrategien legen. In der Zukunft könnten genetische Tests Patientengruppen mit erhöhtem Erkrankungsrisiko identifizieren sowie eine individualisierte und präzisere Medizin ermöglichen.
Genetisch bedingte Aortenerkrankungen – Empfehlungen für Kardiologen in Praxis und Klinik
Authors: Huntgeburth Michael , Neidenbach Rhoia , von Kodolitsch Yskert , Kaemmerer Harald
Published: June 2018

Erweiterungen der Aorta sind häufig. Erst die Kenntnis zugrunde liegender Ursachen und Mechanismen ermöglicht eine adäquate Diagnose und Beratung der Betroffenen. Genetisch bedingte Aortenerkrankungen sind mit einem erhöhten Risiko für Aortenkomplikationen wie Dissektion und Ruptur assoziiert. Die zugrunde liegenden Ursachen können syndromal (z. B. Marfan-, Loeys-Dietz-, vaskuläres Ehlers-Danlos-Syndrom) und nicht syndromal (z. B. isolierte bikuspide Aortenklappe – BAV, Aortenisthmusstenose, komplexe angeborene Herzfehler, familiäres thorakales Aortenaneurysma – FTAA, Dissektionen – TAAD) bedingt sein. Familienanamnese, klinische Merkmale, Bildgebung und genetische Testung werden zur Diagnosestellung herangezogen. Entscheidend ist eine genaue prognostische Einschätzung hinsichtlich möglicher Aortenkomplikationen. Das Management umfasst eine Modifikation der Lebensweise (z. B. bez. körperlicher Belastung bei Sport und Beruf), eine medikamentöse Prophylaxe einer progressiven Aortenerweiterung (Reduzierung der Wandspannung), eine elektive Aortenersatz-OP sowie regelmäßige Nachsorgeuntersuchungen. Aufgrund der Komplexität der Aortopathien ist eine multidisziplinäre Betreuung für eine optimale Patientenversorgung notwendig. Zudem sollte ein Familienscreening von Angehörigen ersten Grades erfolgen, um gefährdete Familienmitglieder identifizieren zu können.
Die Umsetzung des Präventionsgesetzes auf Länderebene: Eine Analyse der Landesrahmenvereinbarungen
Authors: Böhm Katharina , Klinnert Dorothea
Published: June 2018

Hintergrund 2015 wurde in Deutschland erstmals ein Präventionsgesetz verabschiedet. Zur Umsetzung auf Länderebene werden Landesrahmenvereinbarungen (LRVen) zwischen den Sozialversicherungsträgern und den zuständigen Landesministerien getroffen.

Ziel der Arbeit Der Beitrag gibt einen Überblick über die 15 bislang abgeschlossenen LRVen und arbeitet Unterschiede und Gemeinsamkeiten zwischen den Ländern heraus.

Methode Die LRVen wurden einer qualitativen Inhaltsanalyse unterzogen. Hierfür wurden zunächst für jeden Paragraphen Abweichungen von der von den Sozialversicherungsträgern auf Bundesebene konsentierten Mustervorlage festgestellt. In einem zweiten Schritt wurden die Abweichungen einander paragraphenweise gegenübergestellt und Unterkategorien gebildet. Anschließend wurden die Inhalte der Kategorien entsprechend ihrer Merkmalsausprägungen kodiert. Für diesen Beitrag wurden 4 Kategorien ausgewählt: Ziele und Handlungsfelder, Gremien und Regelungsstrukturen, Vorgaben zur Kooperation, sowie Zusammenarbeit mit weiteren Akteuren.

Ergebnisse In einigen LRVen werden über die Ziele der Bundesrahmenempfehlungen hinaus ergänzend landesspezifische Ziele formuliert. Ein Zieleplanungsprozess findet teils innerhalb der LRV-Gremien, teils in breiter angelegten Prozessen statt. Mit 2 Ausnahmen schaffen die LRVen in allen Ländern neue Regelungsstrukturen, welche sich jedoch in ihrer Interaktionsorientierung unterscheiden: in 4 Ländern sind dialogorientierte, in 3 Ländern abstimmungsorientierte und in 7 Ländern entscheidungsorientierte Gremien bzw. Foren in der LRV verankert. Die Vorgaben zur Koordinierung sind in den meisten LRVen weitgehend unverbindlich. Auch die Zusammenarbeit mit dem ÖGD und weiteren relevanten Akteuren wird zumeist nicht oder nur unverbindlich geregelt.

Schlussfolgerungen Die meisten LRVen sind sehr allgemein und wenig verbindlich formuliert; sie definieren lediglich den Rahmen, den es nun auszufüllen gilt. Eine Evaluation der Umsetzung wird daher erst in ein paar Jahren möglich sein.
Genetik von Vorhofflimmern
Authors: Sinner Moritz , Clauss Sebastian , Kääb Stefan
Published: June 2018

Vorhofflimmern ist die häufigste Herzrhythmusstörung und betrifft mehrere Millionen Menschen weltweit. Nachdem in den letzten Jahren bereits ein starker genetischer Einfluss auf die Entstehung von Vorhofflimmern nachgewiesen worden war, konnte eine Studie kürzlich die Heritabilität von Vorhofflimmern mit 22,1% quantifizieren. Klinisch spiegelt sich dies in der Bedeutung der Familienanamnese für Vorhofflimmern wider. Neben seltenen Mutationen, etwa in Ionenkanalgenen, stellen insbesondere häufige genetische Varianten, sog. Single Nucleotide Polymorphisms, einen entscheidenden Faktor der Heritabilität von Vorhofflimmern dar. Mithilfe genomweiter Assoziationsstudien konnten mittlerweile 97 Genorte identifiziert werden, die mit einem erhöhten Risiko für das Auftreten von Vorhofflimmern assoziiert sind. Obwohl die meisten dieser Polymorphismen in der Nachbarschaft von elektrophysiologisch relevanten Genen, kardialen Strukturgenen oder entwicklungsbiologisch relevanten Genen liegen, sind die dem erhöhten Vorhofflimmerrisiko zugrunde liegenden zellulären und molekularen Mechanismen in vielen Fällen unbekannt. Um dies aufzuklären, sind umfangreiche Untersuchungen in zell- und tierexperimentellen Modellen notwendig.
Rupture of the Free Left Ventricular Wall: A Novel Approach for Reconstruction
Authors: Fleißner Felix , Schmitto Jan , Napp L. Christian , Ismail Issam
Published: June 2018

Background A rupture of the free wall of the left ventricle is a rarely seen complication of myocardial infarction and represents an absolute cardiac emergency.

Case Description We hereby present a case of a 64-year-old patient with a rupture of the free left ventricular wall. The patient was treated in an emergent operation with a novel reconstruction method of the left ventricular wall and was discharged 30 days after the initial operation.

Conclusion Left ventricular free wall rupture is rarely described in the literature, which might be because of high mortality in underdiagnosed cases. Therefore, early imaging by echo or computed tomography (CT) is essential for detecting this dangerous condition. Once diagnosed, urgent surgery is mandatory to save the life of the patient.
The Effects of Human Thrombomodulin on the Inactivation of Thrombin by Its Serum Inhibitors
Authors: Thompson E Anne , Salem Hatem H
Published: June 2018

Thrombomodulin is an endothelial cell protein which accelerates thrombin-dependent protein C activation by over 1000 fold. In this study, the effect of thrombomodulin on the inactivation of thrombin by its serum inhibitors was evaluated.

125I-thrombin was incubated at 37° C with serum and the resulting complexes separated by SDS-PAGE. Antithrombin III was the major complex formed with some 125I-thrombin bound to heparin cofactor II and highermolecular weight fractions. Inclusion of thrombomodulin at increasing concentrations inhibited 125I-thrombin binding to antithrombin III and the higher molecular weight fractions but had little effect on thrombin-heparin cofactorII complex formation. Similar results were obtained using a purified antithrombin III/heparin cofactor II system.

Kinetic studies, using purified antithrombin III, revealed that thrombomodulin acts as a weak competitive inhibitor towards antithrombin III (Ki = 39 nM).

We postulate that in the microcirculation, where the ratio of thrombomodulin to antithrombin III is relatively high, thrombin bound to thrombomodulin may be protected from inactivation by antithrombin III and can thus promote efficient activation of protein C.
Multicenter Evaluation of a Chromogenic Substrate Method for Photometric Determination of Prothrombin Time
Authors: Dati F , Barthels M , Conard J , Flückiger J , Girolami A , Hänseler E , Huber J , Keller F , Kolde H -J , Müller-Berghaus G , Samama M , Thiel W
Published: June 2018

A multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories pailicipaled in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x − 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.
Measurement of Low Molecular Weight Heparin Ex Vivo Activities in Clinical Laboratories Using Various Anti-Xa Assays: Interlaboratory Variability and Requirement for an Agreed Low Molecular Weight Heparin Standard
Authors: Sié P , Aillaud M F , Prost D de , Droullé C , Forestier F , Guedj P , Juhan-Vague I , Polack B , Potron G , Roncato M , Roussi J , Sampol J , Aiach M
Published: June 2018

The only sensitive and convenient assay to assess the biological activity of low molecular weight heparins (LMWHs) is based on the potentiation of activated factor Xa inhibition. Several procedures for measuring the socalled anti Xa activity have been proposed. In this collaborative study including eight laboratories, we have used four different assays (three amidolytic and one clotting based methods) for measuring the anti Xa activity of ex vivo samples obtained after injecting three different LMWHs. The dispersion of the results obtained by calibration against standard heparin could be reduced by using any of the three LMWHs for calibration. A coefficient of variation less than 0.20 between values obtained in different laboratories using a variety of methods seems acceptable. However it is necessary to refer to a common international standard for expressing the results in units and to define, for each of the three products, the therapeutic range.
Deaggregation of In Vitro-Degranulated Human Platelets: Irreversibility of Aggregation May Be Agonist-Specific Rather Than Related to Secretion Per Se
Authors: Bauman Joan E , Joachim Reimers H , Heinrich Joist J
Published: June 2018

Based on studies with thrombin, it has been proposed that human platelets exposed to strong release-inducing agents undergo irreversible aggregation and cannot be deaggregated without the use of proteolytic enzymes. We tested the hypothesis that irreversible human platelet aggregation occurs as a result of thrombin-specific platelet alterations rather than induction of the release reaction per se. Washed human platelets were exposed to either thrombin (THR) or the aminophospholipid N-(7-Nitro- 2,1,3-benzoxydiazol-4-yl) phosphatidylserine (NBD-PS) for 20 seconds. Both agents caused similarly extensive release of platelet dense- and α-granule contents. After neutralization of thrombin and NBD-PS, and addition of PGE1 and apyrase, the platelets were sedimented, resuspended and incubated at 37° C with gentle agitation. Single, disc-shaped, degranulated platelets which were recovered in both systems were capable of aggregation in response to a second exposure to aggregating and release- inducing stimuli. Deaggregation was more rapid, more extensive, and more reproducible with NBD-PS- than with THR-degranulated platelets. Platelets exposed to thrombin for longer than 20 seconds showed a progressive loss of deaggregability which was not observed after prolonged incubation with NBD-PS. These findings do not support the concept that extensive secretion per se causes irreversible aggregation of human platelets. Instead it appears that formation of irreversible linkages between platelets involves the specific, time-dependent interaction of THR with platelets, released fibrinogen and possibly one or more other substances secreted from platelets.
The Effect of the Intracellular Calcium Chelator Quin-2 on the Platelet Phosphoinositide Metabolism, Protein Phosphorylation and Morphology
Authors: de Chaffoy de Courcelles D , Roevens P , Verheyen F , Van Belle H , De Clerck F
Published: June 2018

When human platelets prelabeled with [32P] orthophosphate were loaded with Quin-2, the 32P-incorporation in phosphatidic acid, phosphatidylinositol-4 phosphate and phosphatidylinositol-4,5 bisphosphate increased, that in phosphatidylinositol decreased. These effects occurred in a Quin-2-concentration- dependent manner. On stimulation of the serotonin-S2 receptor, signal transduction, measured as changes in labeling in phospholipids and phosphoproteins, was altered in the presence of the fluorophore. Microscopic evaluation illustrated that Quin-2 affected platelet morphology as well in resting as in stimulated platelets. A correlation between platelet shape change and myosin light chain phosphorylation was apparent.

The data evidence that the Quin-2 that is widely used for fluorometric determination of intracellular Ca2+, affects the metabolism of inositol-containing phospholipids whose breakdown is a key event in Ca2i+-mobilization on excitatory platelet activation. These fluorophore-induced alterations might, besides the Ca2-chelating properties, play an important role in the Ca2+ dependent signalling processes in these cells.
Interaction of Thrombin and Factor Xa with Bovine Vascular Endothelial Cells, Smooth Muscle Cells and Rat Hepatoma Cells
Authors: Dryjski Maciej , Kuo Be-Sheng , Bjornsson Thorir D
Published: June 2018

The aims of the present investigation were to characterize the binding and inhibition of thrombin and factor Xa to bovine vascular endothelial cells (EC), bovine smooth muscle cells (SMC), and rat hepatoma cells (RHC), and to evaluate the effects of plasma constituents on their inhibition. The enzymatic activities of bovine thrombin and factor Xa were assayed using chromogenic substrates. After 10 min incubation with the cells, thrombin activity in the solution had decreased by about 20% and was subsequently recovered on the cell surfaces. When the cells with the surface-bound thrombin were incubated with defibrinogenated plasma or antithrombin III (AT-III) for 30 sec only about 10% and 20-40%, respectively, of the initial activity could be recovered. In similar experiments with factor Xa, initial activity in the solution had decreased by 10% after 10 min incubation, and was subsequently recovered from the cell surfaces. After 30 sec incubation with AT-III, no cell surface-bound factor Xa activity was detected, whereas 10% of the bound factor Xa activity was recovered after incubation with defibrinogenated plasma. It is concluded that thrombin and factor Xa are taken up and inhibited by EC, SMC and RHC cell surfaces in similar ratios, suggesting that cell surface-mediated inhibition of clotting factors is not restricted to vascular wall cells. The inactivation of factor Xa was dependent on AT-III, however, the inactivation of thrombin was further promoted by an additional unidentified plasma constituent.
An Approach to Assigning In Vitro Potency to Unfractionated and Low Molecular Weight Heparins Based on the Inhibition of Prothrombin Activation and Catalysis of Thrombin Inhibition
Authors: Ofosu F A , Smith L M , Anvari N , Blajchman M A
Published: June 2018

Unfractionated and low molecular weight (LMW) heparins with good antithrombotic activity invariably catalyze thrombin inhibition and inhibit the appearance of thrombin activity in contact-activated plasma. Conversely, the antithrombotic efficacy of LMW heparins decreases as their ability to catalyze thrombin inhibition and to inhibit the appearance of thrombin activity in plasma decrease. The activated partial thromboplastin time (APTT) has proven a reliable test for assaying unfractionated heparin. We therefore compared 2 unfractionated and 3 LMW heparins on the basis of the minimum concentrations required to double the APTT of normal plasma and by then determined how this anticoagulant effect was achieved. The amount of unfractionated and LMW heparin which doubled the APTT was found to be equivalent to —0.25 antithrombin units. This concentration of each glycosaminoglycan completely inhibited prothrombin activation for 45 s after CaCl2 was added to contact-activated plasma; accelerated thrombin inhibition by purified antithrombin III by approximately 50-fold; and accelerated thrombin inhibition equally by anti thrombin III in undiluted plasma. This concentration of the three LMW heparins increased, by approximately 70fold, the rate of factor Xa inhibition by purified antithrombin III compared to the 50-fold increase seen with the two unfractionated heparins. These results thus suggest that tests based on the inhibition of prothrombin activation and/or on the catalysis of thrombin inhibition provide a useful basis for assigning in vitro potency to both unfractionated and LMW heparins.
Changes in Factor VIII Proteins After Cardiopulmonary Bypass in Man Suggest Endothelial Damage
Authors: Jones D K , Luddington R , Higenbottam T W , Scott J , Cavarocchi N , Reardon D , Calvin J , Wallwork J
Published: June 2018

16 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB) had blood samples taken at various times before, during and up to 1 week after surgery for estimation of beta-thromboglobulin (BTG), alpha- 1-antichymo- trypsin (ACT), factor VIII procoagulant protein (VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin co-factor (vWFiRiCoF). vWF:Ag and vWF:RiCoF rose during and following surgery in a different manner to ACT. At 1 week there was a significantly disproportionate rise in vWF: Ag compared to vWFiRiCoF which suggested a degree of pulmonary endothelial damage.

Prostacyclin, which was administered to 8 of the patients during CPB, reduced platelet activation as measured by a reduction in the release of BTG and also attenuated the consumption of VIII: C. It had no effect on pulmonary endothelial damage as measured by the ratio of vWF: Ag to vWF: RiCoF.
Localization of the Inhibitory Site(s) of Pentosan Polysulphate in Blood Coagulation
Authors: Wagenvoord R , Hendrix H , Soria C , Hemker H C
Published: June 2018

We studied the inhibitory effect of pentosan polysulphate (PPS, Hémoclar®) on thrombin formation in blood coagulation. In contrast to a current hypothesis (1) the anti thrombin III independent effect of PPS on blood coagulation is not caused by preventing the binding of the factors IX, IXa, X, Xa, VIII, V, Va and II onto procoagulant phospholipids.

We investigated the activation by thrombin of factors I, V and VIII. A strong inhibitory effect of PPS on factor VIII activation could be observed. Inhibition of the activation of factor V to the same extent requires about 30-fold higher concentrations of PPS, whereas the activation (clotting) of fibrinogen is not inhibited. The effect of PPS on factor VIIIa is two-fold: A) it inhibits its formation and B) it inhibits its function probably by the formation of a factor VIIIa-PPS complex.

Prothrombinase, constituted of purified factors Xa, Va and phospholipids was not inhibited by PPS, neither were incomplete forms of this enzyme, lacking phospholipids or factor Va. The complete factor X activating enzyme (factors IXa, VIIIa and phospholipids), however, was strongly inhibited, but incomplete forms, lacking factor VIII, were not. The inhibition of the complete enzyme can be explained by reversible binding of PPS to factor VIIIa (causing an inhibition of its function) and it is not an effect on the enzymatic function of the complete enzyme. On saturation of the enzyme with an excess of factor VIIIa no inhibition by PPS is noticed.

We postulate therefore that the antithrombin III independent inhibitory effect of PPS on thrombin generation on blood coagulation is by interaction with factor VIIIa. This effect is additional to the heparin-like action of PPS, i.e. potentiation of the activity of antithrombin III and/or heparin cofactor II. At concentrations attained during therapeutic use the action of pentosan polysulphate on factor VIIIa is the only one that will significantly inhibit the coagulation mechanism.
The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate
Authors: Teitel Jerome M , Ni Hong-Yu , Freedman John J , Garvey M Bernadette
Published: June 2018

Some classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.
Effects of Standard Heparin and a Low Molecular Weight Heparin (Kabi 2165) on Fibrinolysis
Authors: Agnelli Giancarlo , Borm Judocus , Cosmi Benilde , Levi Marcel , Cate Jan Wouter ten
Published: June 2018

Previous and recent reports have suggested a fibrinolysisenhancing property of standard heparin and low molecular weight heparins, but these observations have never been confirmed in a study fulfilling appropriate methodological criteria. The aim of this study was to evaluate the effect of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis in a randomized cross-over double blind placebo controlled study. Six healthy volunteers received intravenously a bolus dose of the following treatments: placebo; standard heparin, 5,000 I.U.; Kabi 2165, 5,000 anti-Xa U; Kabi 2165,10,000 anti-Xa U. Before the injection and at established times thereafter, blood samples were collected for the following assays in plasma: t-PA activity, PA inhibitor activity, fibrin plate lysis area (FPLA), plasminogen, α2-antiplasmin, fibrinogen and anti-Xa activity. Placebo and Kabi 2165, 5,000 anti-Xa U, had no effect on t-PA plasma level. Standard heparin and Kabi 2165, 10,000 anti-Xa U, produced a statistically significant increase in t-PA level at 1 hour after the infusion. This increase lasted for at least 1 hour after the infusion. No effect of any treatment on PA inhibitor, plasminogen, FLPA, α2-antiplasmin and fibrinogen was observed. We conclude that an intravenous bolus dose of both standard heparin, 5,000 I.U. and Kabi 2165, 10,000 anti-Xa U produces a delayed and sustained increase in plasma t-PA.
Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S
Authors: de Fouw N J , de Jong Y F , Haverkate F , Bertina R M
Published: June 2018

summary

The effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.

In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.
Effect of Thrombin on the Production of Plasminogen Activators and PA Inhibitor-1 by Human Foreskin Microvascular Endothelial Cells
Authors: Van Hinsbergh Victor W M , Sprengers Erik D , Kooistra Teake
Published: June 2018

Human foreskin microvascular endothelial cells synthesize and release tissue-type plasminogen activator (t-PA) in similar amounts as do endothelial cells from umbilical cord artery and vein. Human thrombin increases the production of t-PA by these cells, which could be visualized from 8 h after addition of 0.1-5 units/ml thrombin by fibrin autography after SDS polyacrylamide gel electrophoresis of the endothelial cell conditioned media. Thrombin also increased the secretion of t-PA antigen. Together with t-PA, human microvascular cells release urokinasetype plasminogen activator (u-PA) antigen and endothelial cell-type PA inhibitor, PA inhibitor-1, which were both demonstrated by specific immunoprécipitation from radiolabeled endothelial cell conditioned medium. Thrombin increases the release of u-PA antigen, but no u-PA activity could be demonstrated. Thrombin induced a two-fold stimulation of the synthesis and secretion of PA inhibitor-1 antigen. At 0.1 unit/ml thrombin also an increase in PA inhibitor activity was found. At high concentrations of thrombin a decrease of PA inhibitor activity was found, due to the conversion of the active 46 kD PA inhibitor-1 into a 42 kD product without PA inhibitor activity. Our data indicate that interaction of thrombin with microvascular endothelial cells will shift the balance between t-PA, u-PA and PA inhibitor-1, and thus affects the regulation of fibrinolysis.
Influence of Factor Xllla Activity on Human Whole Blood Clot Lysis In Vitro
Authors: Jansen J W C M , Haverkate F , Koopman J , Nieuwenhuis H K , Kluft C , Boschman Th A C
Published: June 2018

We studied the influence of Factor XIII a (F XIII a) activity on the lysis rate of fresh whole human blood clots, without using anticoagulants. Clotting was induced by exogenous thrombin, lysis by tissue-type Plasminogen Activator (t-PA) added before clotting. After various periods of time, lysis rates were determined by measuring the radioactivity in the supernatant of the clot originating from 125I-Fibrinogen added before clotting.

Lysis rates were determined in the presence of endogenous F XHIa and compared with those obtained after specific inhibition of F XIII a activity. We used an IgG fraction of an antiserum quenching the F XIII a activity. Addition of increasing amounts of the antibodies to normal blood resulted in a dramatic increase in clot lysis rate, concomitant with loss of F XIII activity. Lysis of blood clots from a patient with a congenital, homozygous, functional α2-Antiplasmin (α2-AP) deficiency (α2-AP-Enschede) was not or slightly increased by the anti F XIII antibodies indicating that fibrin-fibrin crosslinking per se does not contribute essentially to resistance of the blood clot against fibrinolysis. Both active α2-AP and F XIII a are required for the major part of the F XIII-dependent resistance of whole blood clots against lysis.
In Vitro and In Vivo Pharmacological Profiles of the PAF Receptor Antagonist SRI 63-675
Authors: Handley Dean A , Van Valen Ronald G , Winslow Christine M , Tomesch John C , Saunders Robert N
Published: June 2018

We have examined a recently developed PAF antagonist SRI 63-675 (dimethyl-tetrahydrofuran-methoxyphosphinyloxy-ethylquinolinium) for its ability to inhibit several major PAF-induced physiological responses. The compound was a potent inhibitor of PAF-induced platelet aggregation in platelet rich plasma obtained from humans, guinea pigs, and rabbits, with IC50 values of 3.43, 0.25, and 0.97 μM, respectively. SRI 63-675 did not inhibit ADP, collagen nor epinephrine-induced human platelet aggregation. The IC50 for inhibition of PAF receptor binding to human platelets was 0.37 μM. In the rat SRI 63-675 inhibited 0.1 μg kg-1 i.v. PAF-induced hypotension, with an ED50 of 32 μg kg-1 i.v. Using the same PAF challenge in the guinea pig, SRI 63-675 inhibited the hemoconcentration (ED50 = 17 μg kg-1 i.v.) and bronchoconstriction (ED50 = 24 μg kg-1 i.v.) responses. In the primate, the ED50 was 28 μg kg-1 i.v. against 3.5 μg kg-1 PAF-induced hemoconcentration. The ratio (1:6) in the primate of PAF used (6.3 nmol kg-1) to antagonist at the ED50 (40.7 nmol kg-1) indicates exceptional potency of SRI 63675 in this species. The inhibition by SRI 63-675 of the major PAF-induced effects in the rat, guinea pig and primate suggests a common receptor may be involved in the expression of these PAF responses.
Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture
Authors: Scarabin P Y , Strain L , Ludlam C A , Jones J , Kohner E M
Published: June 2018

During the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.
Identification of Platelet Antigens by Monoclonal Antibodies Using Crossed Immunoelectrophoresis with Immunoblotting of the Monoclonal Antibody
Authors: Thorsen L I , Gaudernack G , Brosstad F , Pedersen T M , Solum N O
Published: June 2018

A method is described for the identification of antigens by monoclonal antibodies. This is applicable whenever precipitating antibodies to the same antigens from a different species are available. The method is based upon: 1) Separation and immunoprécipitation of cellular proteins with a polyspecific antiserum in crossed immunoelectrophoresis in the presence of the non-denaturing detergent Triton X-100 and the monoclonal antibody. 2) Coprecipitation of the monoclonal antibody with its antigen. 3) Subsequent passive transfer of the monoclonal antibody in the antibody-antigen complex onto a nitrocellulose membrane. 4) Visualization of the blotted antibody using an enzyme-linked secondary antibody and a chromogenic substrate. 5) Identification of the corresponding antigen by comparisons to the immunoprecipitate pattern of the original immunoplate. To test this method we have analyzed the detection of the antigens recognized by six previously described monoclonal antibodies against platelet membrane proteins and von Willebrand factor. Specific immunoblots were obtained in each case using small amounts of monoclonal antibodies. Thus, the technique provides an alternative when epitopes are denatured by SDS, and avoids the use of radioactively labelled monoclonal antibodies.
Hageman Factor Activity in Liquoid-Induced Consumption Coagulopathy
Authors: Müller-Berghaus G , Lasch H. G
Published: June 2018

1. Consumption coagulopathy was induced by intravenous injection of Liquoid (sodium polyanetholsulfonate) into rabbits. Thirteen out of 21 animals injected with Liquoid showed fibrin formation in the renal glomerular capillaries characteristic of the generalized Shwartzman reaction. In these 13 animals, a pronounced drop in Hageman factor activity was observed in addition to a decrease in platelet counts and fibrinogen levels.

2. The consumption coagulopathy induced by Liquoid could be prevented by pretreatment of the rabbits with phenprocoumon, a coumarin derivative. None of 21 rabbits pretreated by this anticoagulant and injected with Liquoid showed fibrin in the renal glomerular capillaries. Phenprocoumon pretreatment did not influence the decrease in platelet counts, but it did significantly diminish the drop in fibrinogen levels. Although disseminated intra vascular coagulation and the generalized Shwartzman reaction could be inhibited by phenprocoumon pretreatment, this anticoagulant could not prevent the initial drop in Hageman factor activity after Liquoid injection.

3. Phenprocoumon did not influence the activity or synthesis of Hageman factor. As phenprocoumon pretreatment could not prevent the drop in Hageman factor activity after intravenous injection of Liquoid, it might be concluded that the Hageman factor is either consumed, directly inactivated or destroyed in the animals independent of the presence of the prothrombin complex. These findings support earlier studies which have shown that inhibition of Hageman factor activation in vivo can prevent the generalized Shwartzman reaction induced by Liquoid.
Fibrinolysis Induced by Factor XII Contained in Prothrombin Preparations
Authors: Landaburu R. H , Pernici C , Castellanos D. E
Published: June 2018

Prothrombin products prepared by Seegers procedure induce fibrinolysis when injected intravenously. This property is due to a contaminant denominated Prothrombin Activating Derivative-B, identified as factor XII. The fibrinolytic fraction accompanies prothrombin throughout the purification procedure and may be separated by chromatography on DEAE cellulose.
A Simplified Method for Preparation of Fibrinogen
Authors: Walker Louise , Catlin Avery
Published: June 2018

A method for preparation of fibrinogen from human plasma is presented. The method, a modification of the glycine precipitation procedure of Kazal (6), is simple and rapid, requiring 8 hours or less. The fibrinogen solution is stable on storage in the refrigerator for at least 7 months, represents an average yield of 30-40% of that in the starting material, and is around 95% clottable. Clottability is good even on storage at 37° C for several days; it is generally around 80% clottable after this storage period. The solution is free of plasminogen and plasmin but contains trace amounts of FSF (fibrin stabilizing factor) and factor VIII (factor VIII activity tends to disappear with storage). Ultracentrifugal analysis shows a main peak comprising approximately 95% of the total area (apparent sedimentation coefficient 5.8 × 10-13) and a smaller peak comprising approximately 5% or less of the total area (apparent sedimentation coefficient 3-3.5 × 10−13).