bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarizability of electrically induced magnetic vortex “atoms”
Authors: Karpov P.I. , Mukhin S.I.
Published: July 2018

Electric field control of magnetic structures, particularly topological defects in magnetoelectric materials, draws a great attention, which has led to experimental success in creation and manipulation of single magnetic defects, such as skyrmions and domain walls. In this work we explore a scenario of electric field creation of another type of topological defects – magnetic vortices and antivortices. Because of interaction of magnetic and electric subsystems each magnetic vortex (antivortex) in magnetoelectric materials possesses quantized magnetic charge, responsible for interaction between vortices, and electric charge that couples them to electric field. This property of magnetic vortices makes possible their creation by electric fields. We show that the electric field, created by a cantilever tip, produces a “magnetic atom” with a localized spot of ordered vortices (“nucleus” of the atom) surrounded by antivortices (“electronic shells”). We analytically find the vortex density distribution profile and temperature dependence of polarizability of this structure and confirm it numerically by Monte Carlo simulation.
Composite multiferroic materials consisting of NdFeB and PZT particles embedded in elastic matrix: the appearance of electrical polarization in a constant magnetic field
Authors: Makarova Liudmila , Alekhina Yuliya , Kramarenko Elena , Omelyanchik Alexander , Rodionova Valeria , Malyshkina Olga , Perov Nikolai
Published: July 2018

New composite materials consisting of polymer matrix with PZT and NdFeB microparticles were prepared and investigated in the work. It was found that magnetic properties such as saturation magnetization, coercivity, permeability, depend on mass concentration of the ferromagnetic particles in the samples. Also it was found that all samples had electrical polarization in DC external electric field. The electric properties such as coercivity, remanent polarization, the maximum polarization value, had changes in the external constant magnetic field 1.1 kOe. These changes depended on both concentrations of ferromagnetic and ferroelectric particles. This type of magnetoelectric transformation allows us to classify new materials as multiferroic materials. These new composite materials can easily be prepared of any shape, the final materials are flexible and resistant to external chemical influences. The area of application of new multiferroic materials varies from sensors to autonomous energy sources.
Interplay between magnetism and superconductivity in metallic hydrogen and hydrides at high pressure
Authors: Mazov Lev
Published: July 2018

The detailed analysis of resistive and magnetic measurements with sulfur hydrides at high pressure is performed. The hydrogen system at high pressure can exhibit ferromagnetic (FM) as well as superconducting (SC) properties with layered structure. The onset temperature of resistive transition at 200 K in metallic sulfur hydrides corresponds to magnetic (AF SDW) phase transition rather than SC one. SC transition in these sulfur hydrides occurs only when magnetic (AF SDW) phase transition is over (~ 40 K). The SC mechanism in metallic sulfur hydrides is not conventional but corresponds to Keldysh-Kopaev model characteristic for systems with coexistence of dielectric and SC pairing.
Unconventional phase transitions in strongly anisotropic 2D (pseudo)spin
systems
Authors: Konev Vitaly , Vasinovich Evgeny , Ulitko Vasily , Panov Yury , Moskvin Alexander
Published: July 2018

We have applied a generalized mean-field approach and quantum Monte-Carlo technique for the model 2D S = 1 (pseudo)spin system to find the ground state phase with its evolution under application of the (pseudo)magnetic field. The comparison of the two methods allows us to clearly demonstrate the role of quantum effects. Special attention is given to the role played by an effective single-ion anisotropy ("on-site correlation").
Mechanics of magnetic fluid active element in strong magnetic field
Authors: Polunin V.M. , Ryapolov P.A. , Sheldeshova E.V.
Published: July 2018

Measurements and theoretical analysis of the processes of static displacement and oscillations of the magnetic fluid column confined by magnetic levitation in a strong magnetic field in a horizontally placed tube are carried out. The calculations of the saturation magnetization, made on the basis of the obtained results of the displacement and the oscillation frequency for the sample of the magnetic fluid under study, are in good agreement with the experimental data. The described technique is of interest when studying saturation magnetization, magnetophoresis, aggregation of nanoparticles and their temporal dependence in magnetic colloids.
Magnetic properties and giant magnetoimpedance of surface modified Co-based amorphous ribbons with carbon covering
Authors: Golubeva Elizaveta V. , Chlenova Anna A. , Stepanova Elena A. , Kurlyandskaya Galina V.
Published: July 2018

Fe3Co66Cr3Si16B12and Fe6Co60Ni10Si14B10amorphous ribbons were surface modified in toluene at room temperature. Such a treatment resulted in deposition of thin carbon-based layer. As a result of the carbon covering deposition the stress distribution in the near-surface layers was changed due to partial compensation of the initial quenching stresses. Comparative analysis of magnetic and magnetoimpedance properties of as-quenched and surface modified ribbons confirms changes in effective magnetic anisotropy as a result of surface treatment. An increase of the corrosion resistance of the ribbons with carbon covering can be useful for the development amorphous ribbon based magnetic biosensor.
Current-driven quantum dynamics of toroidal moment in rare-earth nanoclusters
Authors: Plokhov D.I. , Popov A.I. , Zvezdin A.K.
Published: July 2018

The current-driven quantum dynamics of toroidal moment in single molecule magnets with polygonal rare-earth ion core is investigated. The effects of an external current is considered both in equilibrium and in the frames of the Landau-Zener-Stückelberg tunneling model. It is shown that the toroidal moment is a suitable degree of freedom for using the systems in question as qubits in quantum computing.
Non-equilibrium critical behavior of Heisenberg thin films
Authors: Shlyakhtich Maria A. , Prudnikov Pavel V.
Published: July 2018

In this work we study the non-equilibrium properties of Heisenberg ferromagnetic films using Monte Carlo simulations by short-time dynamic method. By exploring the short-time scaling dynamics, we have found thickness dependency of critical exponents z, θ′ and β/v for ferromagnetic thin film. For calculating the critical exponents of ferromagnetic films we considered systems with linear size L = 128 and layers number N = 2; 4; 6; 10. Starting from initial configurations, the system was updated with Metropolis algorithm at the critical temperatures
Quasi-classical localized states in the 2D ferrimagnet
Authors: Panov Yury , Moskvin Alexander
Published: July 2018

We consider highly anisotropic 2D quantum s = 1/2 (pseudo)magnetic system which is equivalent to the frequently used system of charged hard-core bosons on a square lattice. In the continuous quasi-classical approximation, the types of localized excitations are determined by asymptotic analysis and compared with numerical results. Depending on the homogeneous ground state, the excitations are the ferro and antiferro type vortices, the skyrmion-like topological excitations or linear domain walls.
Perovskites: a class of materials with multiple functionalities and applications
Authors: Rossel Christophe
Published: July 2018

First discovered in 1839 by Gustav Rose and named after the Russian mineralogist
L. A. Perovksi, the perovskites have been extensively studied. These materials have
a wide range of properties and many potential applications. The discovery of high
temperature superconductivity in layered copper oxides in the mid-eighties and of
efficient photovoltaic properties in hybrid organic-inorganic perovskite solar cells less
than 10 years ago, have boosted the research efforts on these materials as well as the
number of yearly publications.
The Fortication of Iodine in Salt Consumption Using Manual Gun Spray
Authors: Baroroh Intan , Suwasono Bagiyo , Hardianto Didik
Published: July 2018

The Blue Economy concept begins with Artemia salt farming. The salt farming industry is one of the pillars supporting the economic of coastal community. However, in the market, most of salt consumed have iodine level that is less than 30 ppm. Therefore, it is necessary to measure the supply of iodized salt from the market to reach 30 - 80 ppm iodium according to Indonesia National Standard because it can impact our health. Thus, it was necessary to repair the iodized salt production equipment through an iodine spray device on the machine. The result of spray setting modification technology on macro ranged from 38 - 45 ppm which fulfilled Indonesia National Standard.
A comparison of the water quality between the mangrove areas Mulyorejo and Wonorejo
Authors: Kauhl Luc , Lambregts Kayleigh , Suntoyo
Published: July 2018

The East Coast of Surabaya consists of large mangrove and fish pond areas. These areas are crucial for the ecosystem and for providing food and shelter for the local community. If the water quality decreases the mangroves will not be able to provide these functions. The water quality of these areas can be measured in two ways: by looking at the physico-chemical parameters or by looking at the biological parameters. Both offer a very good view of what state the area is in. The purpose of this study is to find out what the differences are between the Mulyorejo and the Wonorejo areas to see what differences there are within the East Coast of Surabaya and what could be the main cause of these differences. The data shows that the physico-chemical data does not comply with the limitation factors. The main problem are the nutrients which will have to be lowered to preserve the ecosystem. In terms of the biological state of the mangrove, there are few problems found. It is, however, unclear why the tree density in one of the Wonorejo areas is declining and it should be determined what the reason for this is.
Wave energy potency in East Java coast
Authors: Saptono Warpindyasmoro Heri
Published: July 2018

It is predicted that in 2025, Indonesia energy needs is going to reach 280% of current needs. Presently, the renewable energy has only contributed 5.7% of total energy supply. The aim of this research is to investigate wave energy potency in several coasts of East Java which were Pacitan, Jember, Besuki and Tuban. Wave data (significant wave heights and wave periods) were obtained from the ERDDAP server (Environmental Research Division's Data Access Program). Southern East Java Coast showed potency for ocean wave energy resources. The coast of Pacitan had energy of 232 MWh/m/year and the coast of Jember had energy of 190 MWh/m/year.
Trial Test of Fish Attractor “Piknet” Device in Saltwater Fish Tank
Authors: Rosana Nurul , Suryadhi  , Rifandi Safriudin
Published: July 2018

The fish attractor called "Piknet" is an instrument designed based on sound wave to maximize the fishing activity by gill-netters. The sound wave are used in "Piknet" ranged from 100-1000 Hz. The "Piknet" test was conducted to know the range of sound wave which has well responses by salt water fish. The result showed that the sound wave ranged 500 – 1000 Hz is the best one.
Structural Analysis on the Block Lifting in Shipbuilding Construction Process
Authors: Nurul Misbah Muhammad , Hardy Sujiatanti Septia , Setyawan Dony , Chandra Ariesta Rizky , Rahmadianto Satriyo
Published: July 2018

Deformation is unavoidable in some stages of the ship production process. Deformation occurs when the blocks are lifted in an erroneous eye pad position. The aim of this study was to determine behaviour of the ship structures during assembly and lifting process. A typical tanker was used as the basic structural shape. The bottom structures was modeled to be analyzed. In this study, deformations and stresses on the bottom structures during the block lifting are investigated using the finite element method. The deformations and stresses are evaluated and critical condition detected. The preferable block lifting method with the minimum distortion on the bottom structures of tanker is proposed.
Cost and time analysis of graving dock project
Authors: Silvianita  , Aprillia Nur , Mulyadi Yeyes , Citrosiswoyo Wahyudi , Suntoyo
Published: July 2018

The construction of new shipyard in the Cilacap area is one of the best ways to reduce the accumulation of vessels. The construction of shipyard has many risks, one of the risks that can occur during the construction of the shipyard is in terms of cost and time. Project scheduling is a tool to make sure the project finished on time. This paper discusses project scheduling and cost calculation using Critical Path Method (CPM) and Program Evaluation Review Technique (PERT) method for Graving Dock project development in Cilacap. Project scheduling is useful to indicate the relation of each activity to another. This paper will discuss the critical activities during Gravity Dock development and the duration for the whole project using CPM. The next step is to determine the probability of the completing project that can be finished within the time frame using PERT. Based on the CPM analysis, the probability of Graving Dock project can be finished in 204 days is 79,81 %. The total cost for Graving Dock project in Cilacap is Rp. 6.486.122.769.
Chronisch entzündliche Darmerkrankungen: Leitsymptome und Diagnostik
Authors: Lissner Donata , Sonnenberg Elena , Siegmund Britta
Published: July 2018

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, often occur early in life. Therefore, they affect our patient’s individual path of life, their ability to work and the quality of life tremendously, which calls for close and comprehensive medical care. This article features 5 cardinal signs and their diagnostics.
Der Einsatz von Idarucizumab bei intrazerebraler Blutung – Ein Fallbericht
Authors: Hummel Björn , Senger Sebastian , Schleicher Christian , Eichler Hermann
Published: July 2018

Anamnese und klinischer Befund Aufnahme eines 82-jährigen Patienten mit Verdacht auf zerebrale Blutung nach häuslichem Sturz unter Dauerantikoagulation mit Dabigatran wegen Vorhofflimmern.

Untersuchungen Die kraniale Computertomografie zeigte beidseitige chronische Subduralhämatome mit frischen Blutanteilen eines ausgedehnten, linksseitigen Subduralhämatoms und Mittellinienverlagerung. Die Laboranalyse ergab eine nur mäßig hohe Dabigatran-Konzentration bei durchlaufender Thrombinzeit.

Diagnose Sturzbedingte intrazerebrale Blutung und chronisches Subduralhämatom unter Antikoagulation.

Therapie und Verlauf Präoperative Gabe von Idarucizumab zur Antagonisierung von Dabigatran und neurochirurgische Hämatom-Evakuation mit rückläufiger Mittellinienverlagerung. Heparinisierung und Wiederaufnahme der Dabigatran-Behandlung nach Rehabilitation in klinisch stabilem Verlauf bei neurologisch geringgradigen Residuen.
Length of stay overestimates severity of post-ERCP pancreatitis: Is it time to revise the consensus definition?
Authors: Faghih Mahya , Sinha Amitasha , Moran Robert , Afghani Elham , Patel Yuval , Storm Andrew , Kamal Ayesha , Akshintala Venkata , Zaheer Atif , Kalloo Anthony , Kumbhari Vivek , Khashab Mouen , Singh Vikesh
Published: July 2018

Introduction Length of stay (LOS) is an important determinant of the severity of post-ERCP pancreatitis (PEP) in the consensus definition. The aim of our study was to evaluate and compare severity of PEP based on the revised Atlanta classification (RAC) and the consensus definition.

Patients and methods Between 1/2000 and 12/2011, all adult patients admitted with suspicion of PEP after outpatient ERCP were evaluated. PEP was defined using the RAC, but the severity of PEP was defined using both revised Atlanta and consensus definitions.

Results A total of 341 patients (mean age 49 years and 75 % females) were diagnosed with PEP. The consensus definition classified 57 %, 37 %, and 8 % of patients with mild, moderate, and severe PEP, respectively. The RAC diagnosed 94 %, 6 %, and 0 % with mild, moderate, and severe acute pancreatitis, respectively. Of the patients diagnosed with moderate-severe PEP by consensus definition, only 12.5 % had clinical parameters of pancreatitis severity, such as acute fluid collection(s), pancreatic necrosis, transient organ failure and/or required percutaneous or surgical drainage, while 87.5 % were classified only based on a LOS ≥ 4 days. The most common reason for increased LOS was persistent post-procedural abdominal pain in 47 % of patients, followed by other reasons not related to pancreatitis in 17 %.

Conclusion The consensus definition overestimates the rates of severe PEP when compared to the RAC. The majority of PEP patients classified as moderate-severe PEP have extended LOS, due to post-procedural abdominal pain rather than complications of PEP.
Die Implementierung medizinischer Einsatzteams als Beitrag zur Verbesserung der perioperativen Patientensicherheit. Wer? Wann? Wie?
Authors: Schewe Jens-Christian , Lenkeit Stefan , Ganser Janina , Heller Axel R. , Koch Thea
Published: July 2018

Im Gegensatz zur präklinischen Notfallmedizin existieren in Deutschland bis heute keine vergleichbaren fest etablierten Strukturen oder gesetzliche Vorgaben zur Aufbau- und Ablauforganisation sowie Personalqualifikation und Ausstattung der innerklinischen Notfallversorgung. Bei perioperativen Patienten treten unerwartete Komplikationen auf Normalstation jedoch relativ häufig auf. Oft sind bereits Stunden vor einem möglichen kritischen Ereignis Warnzeichen für eine Verschlechterung zu erkennen, wobei diese zu oft unbemerkt bleiben und es im Verlauf zu vermeidbaren schwerwiegenden Komplikationen oder Herz-Kreislauf-Stillständen kommen kann. Zur Verbesserung der innerklinischen Versorgungsstruktur und zur Vermeidung von innerklinischen Herz-Kreislauf-Stillständen dient die Etablierung sog. medizinischer Einsatzteams (engl. medical emergency teams). Dieser werden im Sinne eines präventiven Therapieansatzes bei erkennbaren Abweichungen der Vitalparameter frühzeitig alarmiert.
Durch diesen präventiven Therapieansatz können innerklinische Kreislaufstillstände und ungeplante Aufnahmen auf eine Intensivstation vermieden und die perioperative Patientensicherheit erhöht werden.
Periphere arterielle Verschlusskrankheit: Wann ist ein PCSK9-Inhibitor sinnvoll?
Authors: Kröger Knut , Espinola-Klein Christine , Hoffmann Ulrich , Kalka Christoph , Lawall Holger , Weiss Norbert
Published: July 2018

Die Leitlinie der Europäischen Gesellschaft für Kardiologie empfiehlt bei Patienten mit manifester peripherer arterieller Verschlusskrankheit (PAVK) ebenso wie bei KHK oder zerebrovaskulärer Erkrankung einen LDL-C-Zielwert < 70 mg/dL oder eine Reduktion um 50 %, wenn der Ausgangswert zwischen 70 und 135 mg/dL liegt. Die Applikation eines PCSK9-Inhibitors ermöglicht die Zielwerterreichung für viele Patienten, die dies unter einer maximalen Statintherapie in Kombination mit Ezetemib nicht erreichen. In der Fourier-Studie konnte für Patienten mit PAVK, die bei Studieneinschluss weder einen Myokardinfarkt noch einen Apoplex erlitten hatten, eine deutliche Risikoreduktion (RR) sowohl der kardiovaskulären (RR = 0,67; 0,47 – 0,96; p = 0,0283) als auch der die Extremität betreffenden Endpunkte (RR = 0,43; 0,19 – 0,99; p = 0,042) erreicht werden. Diese Patienten werden insbesondere bei Fachärzten für Angiologie erkannt und diese Facharztgruppe ist im GBA-Beschluss als Verordner speziell genannt.
Divergent Reactivity of Indole-Tethered Ynones with Silver(I) and Gold(I) Catalysts: A Combined Synthetic and Computational Study
Authors: Lynam Jason , Taylor Richard , Unsworth William , Liddon John , Rossi-Ashton James , Clarke Aimee
Published: July 2018

A combined synthetic and computational (DFT) study has been performed to account for the divergent reactivity of indole-tethered ynones when treated with Ag(I) and Au(I) catalysts. The two catalyst systems deliver spirocyclic indolenines and carbazoles, respectively, from the same precursors, with the reaction outcomes believed to be a result of differences in the rates of a key protodemetalation step. A ring-opening/ring-closing isomerisation process is proposed to enable the interconversion of spirocyclic and C-2 annulated indole intermediates, in contrast to the 1,2-migration mechanism tentatively proposed in previous studies.
Enhancement of Spontaneous Fibrinolytic Activity in Diabetic Retinopathy
Authors: Ostermann Helmut , Tschöpe Diethelm , Greber Wolfgang , Meyer-Rüsenberg Hans-Werner , van de Loo Jürgen
Published: July 2018

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.
The Production of a Factor X Activator by a Methylcholanthrene-Induced Rat Fibrosarcoma
Authors: Pangasnan Rosanna S , Devereux Dennis , DeCunzo Louis P , Karp George I
Published: July 2018

The association between neoplasia and thrombosis has been well documented. We have studied the production of a procoagulant which is a factor X activator in a rat fibrosarcoma model. Extracts of excised tumor were assayed in a one stage clotting assay using normal and factor deficient human plasmas. The activity was not due to tissue factor, as acceleration of clotting was observed in FVII deficient plasma. No activity was noted in FX deficient plasma. The activator was capable of cleaving 125I-FX in the absence or presence of calcium. A radioimmunoassay (RIA) demonstrated a 5,100-fold increase in the levels of FX activation peptide after exposure to sarcoma extract. The FX activation occurs in the absence of calcium although the effect is greatly accelerated in the presence of 5 mM CaCl2. Using a two-stage amidolytic assay, functional activation of FX by the sarcoma was demonstrated. Inhibitor studies suggest that the sarcoma-derived procoagulant is a serine protease. The methylcholanthrene-induced rat sarcoma may serve as a useful model for investigating the regulation and effects of cancer procoagulants.
Two New Nonsense Mutations in Type Ia Antithrombin III Deficiency at Leu 140 and Arg 197
Authors: Tomonari Akira , Iwahana Hiroyuki , Yoshimoto Katsuhiko , Shigekiyo Toshio , Saito Shiro , Itakura Mitsuo
Published: July 2018

Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, the molecular basis of hereditary type la antithrombin III (AT III) deficiency was disclosed in two families. One mutation was a change from T to A in the codon of TTA for Leu 140 forming a stop codon of TAA, which was confirmed by mutated primer-mediated PCR-HindIII digestion. The application of this method demonstrated that all four affected members had the mutant allele in a heterozygous state and that none of unaffected subjects had this mutation. Another mutation in the second family was a change from C to T in the codon of CGA for Arg 197 also forming a stop codon of TGA, which was confirmed by PCR-HaeIII digestion. Based on these, it was concluded that the two new nonsense mutations in the AT III gene in a heterozygous state are the molecular basis of hereditary type Ia AT III deficiency.
Fibrinolytic Potential and Antiphospholipid Antibodies in Systemic Lupus Erythematosus and Other Connective Tissue Disorders
Authors: Jurado M , Páramo J A , Gutierrez-Pimentel M , Rocha E
Published: July 2018

We studied the fibrinolytic response before and after venous occlusion (VO) in 30 patients with systemic lupus erythematosus (SLE), 25 with rheumatoid arthritis (RA) and 25 with different connective tissue disorders. Results were compared in patients with and without antiphospholipid antibodies (APA) and a history of either thrombosis or abortions. Before occlusion plasma levels of tissue-type plasminogen activator (t-PA) antigen and its inhibitor (PAI-1) were significantly higher in the patient group (p <0.001). After occlusion, a low fibrinolytic activity on fibrin plates (p <0.005) was observed in the same group. t-PA capacity and t-PA release were similar in relation to controls. The plasma PAI-1 activity was significantly elevated in each group of patients (p <0.005) as compared to the control group. No significant differences with respect to t-PA and PAI-1 were observed in patients as to the presence or absence of thrombosis. There was also no correlation between the fibrinolytic changes and the presence of APA. It is concluded that an impairment of the fibrinolytic system, mainly related to increased PAI-1 levels, is present in most patients with connective tissue disorders, although these changes did not correlate with the presence of APA or the incidence of thrombosis.
Cigarette Smoking Increases Thromboxane A2 Formation without Affecting Platelet Survival in Young Healthy Females
Authors: Dotevall Annika , Rångemark Christina , Eriksson Elsa , Kutti Jack , Wadenvik Hans , Wennmalm Åke
Published: July 2018

Smoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinor-thromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20–46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p <0.05), while plasma and urinary β-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p <0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.
Treatment of Venous Thromboembolism in Patients with Congenital Deficiency of Antithrombin III
Authors: Schulman S , Tengborn L
Published: July 2018

The treatment course of all thromboembolic events in the patients with congenital deficiency of antithrombin III (AT III) in the national Swedish register was reviewed in order to assess the appropriate medical therapy in this situation. The medical treatment of 70 events of venous thromboembolism was evaluated. There were eight cases with signs of clinical progression. The risk of therapeutic failure with heparin could be as low as 1.5% or as high as 9.2%. It would not be cost-effective to substitute with concentrates of AT III in every case with congenital deficiency thereof in connection with acute venous thromboembolism. “Heparin resistance” does not seem to be a problem in the vast majority of these patients.
Vitronectin Modulates Glycosaminoglycan Dependent Reactions of Protein C Inhibitor
Authors: Seiffert Dietmar , Geiger Margarethe , Ecke Sonja , Binder Bernd R
Published: July 2018

Protein C inhibitor (PCI), a glycosaminoglycan (GAG) dependent serine protease inhibitor, inhibits its target proteases by forming SDS-stable 1:1 complexes. GAGs alter target enzyme specificity of PCI in such a way that e.g. urokinase (uPA) is the preferred target enzyme in the presence of GAGs while in their absence preferentially tissue kallikrein (TK) complexes are formed.

The effect of the GAG-binding adhesive glycoprotein vitronectin (Vn) on the GAG-stimulated inhibition of uPA by PCI was studied using an amidolytic assay. In the presence of heparin, Vn protected uPA from inhibition by PCI in a dose-dependent manner with respect to both, Vn- and heparin-concentration. Vn also was active when heparin was replaced by low-molecular weight heparin or heparan sulfate, respectively. In the absence of GAGs, Vn had no effect on the inhibition of uPA by PCI.

In a similar system, Vn was far less effective in modifying the inhibitory function of heparin on the inhibition of TK by PCI. When equimolar concentrations of radiolabelled uPA and TK were incubated with PCI in the presence of heparin, only complexes of PCI with uPA were detectable. Addition of Vn reduced this complex formation, whereas, in contrast, complexes of PCI and TK appeared. These results indicate that Vn modulates both, the activity and specificity of PCI and suggest different structural heparin-requirements for the PCI/uPA versus PCI/TK interaction.
Expression of Urokinase and Its Receptor in Invasive and Non-Invasive Prostate Cancer Cell Lines
Authors: Hollas W , Hoosein N , Chung L W K , Mazar A , Henkin J , Kariko K , Barnathan E S , Boyd D
Published: July 2018

We previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 106 cells per 48 h) than DU-145 cells (63 ng/ml per 106 cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.
Treatment of Hypertension Induces a Fall in Platelet Basal Cytoplasmic Calcium Concentration without Influencing Platelet Aggregation
Authors: Wilson J , Orchard M A , Prentice C R M , Lees A D , Baig M W , Perrins E J , Davies J A
Published: July 2018

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76–181) to 73 (60–83) nM, which was similar to the median value of 70 (61–80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.
Changes in G-Actin after Platelet Activation in Platelet Rich Plasma
Authors: Heptinstall S , Glenn J , Spangenberg P
Published: July 2018

We have used the DNase I inhibition assay to study changes in G-actin after platelet activation in platelet-rich plasma (PRP) induced by ADP. Because of problems associated with depolymerization of F-actin after lysis of ADP-activated platelets in the presence of plasma, G-actin was measured using a lysis buffer that contained formaldehyde to prevent any depolymerization of F-actin.

Different patterns of response were seen depending on the concentration of ADP used, and these were modified by avoiding aggregation by either not stirring the sample or by adding EDTA. The results show rapid conversion of G-actin to F-actin in association with shape change, and there is a further decrease in G-actin associated with irreversible platelet aggregation. Thus evidence is presented that actin polymerization occurs in two phases after ADP stimulation.
Congenital Histidine-Rich Glycoprotein Deficiency
Authors: Shigekiyo Toshio , Ohshima Tsutomu , Oka Hirofumi , Tomonari Akira , Azuma Hiroyuki , Saito Shiro
Published: July 2018

The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. A month after stopping the drug, her plasma activities of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and plasminogen activator inhibitor were normal, but her plasma histidine-rich glycoprotein (HRG) level was only 21% of the normal level of 109.5 ± 51.5% (mean ± 2 SD). The HRG concentrations in her plasma determined on four different occasions over 6 months were similar. She showed no clinical signs of liver insufficiency or sepsis. Low levels of plasma HRG (20% to 35% of normal) were also found in her aunt, uncle and two daughters. These results suggest that congenital HRG deficiency is inheritary in this family.
Effects of Hirudin on Activated Partial Thromboplastin Time Determined with Ten Different Reagents
Authors: Tripodi Armando , Chantarangkul Veena , Arbini Arnaldo A , Moia Marco , Mannucci Pier Mannuccio
Published: July 2018

Hirudin prolongs the APTT when added to normal plasma and the extent of prolongation depends on the type of reagent used. The aim of this study was to compare the dose-response curves of 10 widely used APTT reagents for linearity and parallelism. On each of 10 working days a normal pooled plasma was mixed with increasing amounts of recombinant hirudin (HBW023) ranging from 0 to 5 μg/ml and tested for APTT by photo optical coagulometer. Within each working day, clotting times were measured in duplicate and the order of testing with each reagent was changed every day. Results were expressed as ratios of clotting times with hirudin to clotting times without hirudin, and the values plotted against the hirudin concentration on a log-log scale. The dose-response curves for all reagents were linear over 0.3–1.2 μg/ml. The reagent-related slopes ranged from 0.225 ± 0.003 to 0.303 ± 0.003 (mean ± SE) and were significantly different. Precision studies indicated that the least sensitive reagent was also the least precise. These findings indicate that the clotting time values obtained for patients treated with hirudin will vary depending on the APTT reagent used.
On the Mechanism of Coagulation Inhibition on Surfaces with End Point Immobilized Heparin
Authors: Elgue G , Blombäck M , Olsson P , Riesenfeld J
Published: July 2018

A well established technique to improve blood compatibility of artificial materials for use in the circulation is to coat the surface with heparin. The present report describes the antithrombin mediated inhibition of thrombin and factor Xa by surfaces modified with end point immobilized heparin. The reaction was followed by conventional chromogenic substrate based enzyme assays as well as by immunological measurement of the enzyme inhibitor (thrombin-antithrombin) complex formation. Both enzymes were rapidly inactivated by heparin surfaces after selective presaturation with antithrombin on the immobilized high affinity heparin molecules. The thrombin inhibitory capacity was enhanced when both high and low affinity heparin were preadsorbed with inhibitor. The main part of the thrombin-antithrombin complex formed remained bound to the surface, however, without functionally blocking the activity of the high affinity sequence of the immobilized heparin.

Aliquots of recalcified plasma were slowly rotated in loops of heparinized tubing to investigate whether the main thromboresistant function of the surface was exerted at the level of thrombin or by inactivation of preceding enzymes. After 1 h no visible clotting occurred and only trace amounts of thrombin (0.07 IU/ml), measured as thrombin-antithrombin complexes, had been formed. In non-heparinized loops and in the test tube plasma clotted after 20 min. The thrombin generation when clotting occurred was in the order of 10 IU/ml. It is concluded that the immobilized heparin mediates inhibition of the coagulation cascade prior to prothrombin activation.
Pharmacokinetics of Saruplase, a Recombinant Unglycosylated Human Single-Chain Urokinase-Type Plasminogen Activator and Its Effects on Fibrinolytic and Haemostatic Parameters in Healthy Male Subjects
Authors: de Boer A , Kluft C , Gerloff J , Dooijewaard G , Günzler W A , Beier H , van der Meer F J M , Cohen A F
Published: July 2018

Pharmacokinetics of two doses of the recombinant single-chain urokinase-type plasminogen activator (r-scu-PA) saruplase (40 and 20 mg) and its effect on fibrinolytic and haemostatic parameters were studied in six healthy male subjects using a randomized, double-blind, placebo-controlled, cross-over study. Special precautions were taken to prevent artefactual in vitro effects on fibrinolytic activity.

The clearance of saruplase ranged from 310 to 862 ml/min and the apparent volume of distribution of the central compartment was about 8 1. Both doses of saruplase caused α2-antiplasmin consumption, indicating some systemic fibrinolytic activation. However, the 20 mg dose caused no detectable fibrinogen breakdown and only a small increase in total fibrin/fibrinogen degradation products (TDP) (from 0.16 μg/ml [range 0.14 to 0.19] to 0.78 μg/ml [range 0.56 to 1.26]), while the 40 mg dose produce a fibrinogen breakdown to an average value of 44% (range 19 to 60%) and TDP increased from 0.12 μg/ml (range 0.11–0.12) to 2.29 μg/ml (range 0.45 to 5.55). The breakdown of fibrinogen was related to the quantity of saruplase converted to active two-chain u-PA (tcu-PA) in vivo (6 to 22% conversion). There were no important effects of saruplase on overall blood coagulation (activated partial thromboplastin time) and platelet function (collagen induced platelet aggregation, urinary [2,3-dinor]-thromboxane B2 excretion and plasminogen activator inhibitor 1 [PAI-1] release from platelets).

Saruplase is cleared rapidly from the plasma and a variable amount is converted to tcu-PA. This two-chain form of u-PA probably causes the dose-dependent systemic fibrinolytic activation.
Risk of Hepatitis A in Dutch Hemophilia Patients
Authors: Mauser-Bunschoten E P , Zaaijer H L , van Drimmelen A A J , Berg H M van den , Roosendaal G , Lelie P N
Published: July 2018

Recently, clotting factor preparations transmitted hepatitis A virus (HAV) to hemophilia patients. To study the risk of HAV infection in Dutch hemophilia patients, serum samples of 341 patients with hemophilia were tested for HAV antibodies (anti-HAV).

197/341 patients (group 1) were treated with clotting factor concentrates produced from large plasma pools, 144/341 patients (group 2) were treated with small pool cryoprecipitate. The test results were compared to those of healthy blood donors (n = 19,746) of the same age. In addition stored serum samples (1983-1994) from hemophilia patients were tested for HAV antibodies.

No increased risk of HAV infection was found in Dutch hemophilia patients. The anti-HAV prevalence in group 1 was 20%, in group 213% and in blood donors 41%. A significantly (p <0.002) lower percentage of HAV antibodies was found in hemophilia patients born in the 1950s using cryoprecipitate (11%) as compared to blood donors of the same age (40%), probably caused by passive administration of anti-HAV through clotting product. Passive immunization in the past was significantly (p <0.02) more often found in group 2 (41.7%) than in group 1 (28%).

In the period 1983 till 1988 five seroconversions were seen in group 1 (2%) and one in group 2 (0.7%). Anti-HAV seroconversions were not observed after 1988.

In a risk analysis we estimated that 2 plasma pools of 10,000 Dutch blood donors per year may contain HAV. The absence of HAV among Dutch hemophilia patients suggests that this contamination is successfully inactivated.
von Willebrand Factor, Soluble P-Selectin, Tissue Plasminogen Activator and Plasminogen Activator Inhibitor in Atherosclerosis
Authors: Blann A D , Dobrotova M , Kubisz P , McCollum C N
Published: July 2018

Tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (IHD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman’s correlations between tPA and vWf (r = 0.37, p <0.001), tPA and triglycerides (r = 0.38, p <0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.
Physiological Effects of Nonimmune Platelet Associated Immunoglobulin G
Authors: Sugiura K , Steiner M , Baldini M
Published: July 2018

The function of nonimmune IgG associated with platelets is unknown. In a series of experiments we have investigated this problem, relating amount of platelet-associated IgG (PAIgG) to platelet volume, serotonin release, adherence of platelets to monocytes and platelet senescence. Most of these studies were performed with human platelets. Platelets freed of preexisting PAIgG by incubation at 22° C were incubated with IgG in a series of concentrations ranging from 0.4 — 27.0 X10-6 M. The IgG preparations used were demonstrably free of aggregated forms of the protein. The amount of PAIgG bound to platelets was determined by the use of fluorescein isothiocyanate-conjugated anti-IgG antibody (F-anti-IgG antibody) which was quantified in a fluorospectrophotometer. Newly bound IgG was assayed similarly by the use of F-IgG. A dose-dependent increase in platelet volume was associated with the binding of nonimmune IgG by platelets. The process which leveled off at an IgG concentration of 1.2 —1.5 X10-5 M was almost fully reversible and was not due to platelet shape change or aggregation. Release of serotonin from IgG-treated platelets was relatively small but to the extent that it occurred was positively related to the IgG concentration to which platelets were exposed. Adherence to autologous monocytes studied quantitatively by the use of formaldehyde-fixed cells was also positively related to the amount of IgG on the platelets. Normal or IgG-defident serum had a potent inhibitory (noncompetitive) action on the binding of F-IgG and F-anti-human IgG antibody to human platelets. Cohorts of platelets prepared in rabbits during the recovery phase of immunological thrombocytopenia induced by injection of heterologous antiserum, showed an age-dependent increase of PAIgG and of IgG binding. These results suggest that PAIgG plays a role in the clearance of senescent platelets.
International Collaborative Study on the Assay of Commercially Available High and Low Molecular Weight Urokinases
Authors: Gaffney P J , Tydeman S M , Kirkwood T B L , Aronson D , Murano G
Published: July 2018

Urokinases of different molecular weights are now commercially available. An international collaborative study (eight laboratories) has been conducted to investigate the effect of type and concentration of plasminogen on the assay of two different urokinase preparations against the International Reference Preparation (IRP). Considerable inter-laboratory variation in relative potency estimation was found, and a small effect of plasminogen concentration, independent of type, was apparent.
Daunorubicin and Platelet Function
Authors: Pogliani M E , Fantasia R , Lambertenghi-Deliliers G , Cofrancesco E
Published: July 2018

The influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.

Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.

Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.

The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.

This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.