bluuebunny/crossref_metadata_2025 huggingface dataset:
Cobalt nanocomposites on N-doped hierarchical porous carbon for highly selective formation of anilines and imines from nitroarenes
Authors: Song Tao , Ren Peng , Duan Yanan , Wang Zhaozhan , Chen Xiufang , Yang Yong
Published: July 2018

A heterogeneous, active, and non-noble cobalt nanocomposite for selective synthesis of aniline derivatives and imines from nitroarenes is reported.
Antibacterial properties and clinical potential of pleuromutilins
Authors: Goethe Olivia , Heuer Abigail , Ma Xiaoshen , Wang Zhixun , Herzon Seth B.
Published: July 2018

A critical review of the chemistry, biology, and clinical development of pleuromutilin-based antibiotics is presented.
Insights into the spontaneous formation of hybrid PdOx/PEDOT films: electroless deposition and oxygen reduction activity
Authors: Vigil Julian A. , Brumbach Michael T. , Duay Jonathon , Lambert Timothy N.
Published: July 2018

Hybrid PdOx/PEDOT films efficiently catalyse the direct 4e− oxygen reduction reaction in alkaline electrolyte.
Surface-enhanced Raman spectroscopic identification in fingerprints based on adhesive Au nanofilm
Authors: Lin Jieru , Zhang Chenjie , Xu Minmin , Yuan Yaxian , Yao Jianlin
Published: July 2018

A facial approach was developed successfully for transferring and recovering the pattern of fingerprints based on surface enhanced Raman spectroscopy and adhesive Au nanofilm.
Construction of 2D/2D layered g-C3N4/Bi12O17Cl2 hybrid material with matched energy band structure and its improved photocatalytic performance
Authors: Shi Lei , Si Weiwei , Wang Fangxiao , Qi Wei
Published: July 2018

Surface-to-surface contact g-C3N4/Bi12O17Cl2 hybrid material with a matched energy band structure could efficiently transfer photoinduced charges, improving the photocatalytic activity.
Apigenin ameliorates vascular injury in rats with high fructose-induced metabolic disturbance by inhibiting PI3K/AKT/GLUT1
Authors: Chen Xiaofang , Tan Jianyang , Zhang Lu , Liu Yonggang , Cheng Yahong , Zhang Qianying , Ding Hong
Published: July 2018

(A) Chemical structure of apigenin. (B) Graph illuminating the experimental design for the time course of fructose and apigenin administration, and the timelines for the histological studies, biochemical analysis and western blot analysis.
Anisotropic growth of gas–liquid precipitated ceria mesocrystals to wires several micrometers in length
Authors: Kubota Yuta , Kishi Tetsuo , Yano Tetsuji , Matsushita Nobuhiro
Published: July 2018

CeO2 wires several micrometers in length were formed through anisotropic growth of mesocrystals by oriented attachment on {111} surfaces.
Catalytic decarbonylation of stearic acid to hydrocarbons over activated carbon-supported nickel
Authors: Zhang Zihao , Chen Zhe , Chen Hao , Gou Xin , Chen Kequan , Lu Xiuyang , Ouyang Pingkai , Fu Jie
Published: July 2018

Highly efficient production of hydrocarbons from the decarbonylation of stearic acid in the absence of H2 over Ni/AC.
Ultralayered core–shell metal oxide nanosheet arrays for supercapacitors with long-term electrochemical stability
Authors: Han Dandan , Shen Ye , Pan Yifan , Cheng Zhenyu , Wei Yen , Zeng Guangjian , Mao Liucheng
Published: July 2018

As a supercapacitor electrode material with good electrochemical performance, the prepared ultralayered Co3O4@NiO core/shell nanosheet array electrode demonstrated a notably enhanced specific capacitance.
On the dynamics of transition metal migration and its impact on the performance of layered oxides for sodium-ion batteries: NaFeO2as a case study
Authors: Silván Begoña , Gonzalo Elena , Djuandhi Lisa , Sharma Neeraj , Fauth François , Saurel Damien
Published: July 2018

Reversibility of transition metal migration in layered oxides as cathodes for sodium ion batteries at the expense of polarization increase.
Titanium-based implant comprising a porous microstructure assembled with nanoleaves and controllable silicon-ion release for enhanced osseointegration
Authors: He Xiaojing , Zhang Xiangyu , Li Jianfang , Hang Ruiqiang , Huang Xiaobo , Yao Xiaohong , Qin Lin , Tang Bin
Published: July 2018

Osseointegration is crucial for early fixation as well as for long-term implantation success, hence numerous efforts have been made to tune the surface topography or chemical composition of biomedical implants to improve osseointegration.
Isoindigo benzodifurandione based conjugated polymers for high performance organic field-effect transistors
Authors: Takaya Tomotsugu , Mamo Melaku Dereje , Karakawa Makoto , Noh Yong-Young
Published: July 2018

We report isoindigo based copolymers, poly(isoindigo benzodifurandione-bithiophene-alkoxyl) (PIBDF-BTO) and poly(isoindigo-bithiophene-alkoxyl) (PI-BTO) for high performance organic field-effect transistors (OFETs).
Exploring novel bismuth-based materials for energy storage applications
Authors: Li Feng , Jiang Tao , Zhai Jiwei , Shen Bo , Zeng Huarong
Published: July 2018

A novel bismuth-based material of hot-pressed (Bi0.5K0.5)TiO3–0.06La(Mg0.5Ti0.5)O3 ceramic with an ultrahigh energy storage density and fast discharge speed.
Evaluation of the stability of cadmium [Cd] in slags from the Waste Thermal Treatment Plant [WTTP] in Kraków
Authors: Kosa-Burda Beata , Kicińska Alicja
Published: July 2018

The purpose of the research was to evaluate the mobility of cadmium [Cd] in slags from municipal waste incineration. The evaluation was based on TVA's two-stage wash-out test on fresh samples and on samples exposed to atmospheric factors’ influence for a period of two weeks. The tested slag samples were collected from the municipal Waste Thermal Treatment Plant [WTTP] in Kraków. Total Cd content in the waste was determined by the decomposition of samples in aqua regia. The Cd concentration in post-extraction solutions was determined by the AAS method. On the basis of the obtained results, it was found that prolonged contact with water causes leaching (washing out) of significant amounts (5.6–11.8% of the total content) of the element from the tested fresh waste. Prolonged contact with water, together with the influence of other atmospheric factors (temperature changes, sunshine, wind), has a negative influence on Cd stability in the examined waste, causing the release of significant amounts of that element into the surroundings, which may pose a threat to the environment.
Seasonality of water supply network failure in the aspect of water supply safety
Authors: Piegdoń Izabela , Tchórzewska-Cieślak Barbara
Published: July 2018

Many phenomena are characterized by unevenness and variability in time, so-called periodic fluctuations, of which seasonal variations are a special case. In water supply systems, the failures of water pipes are also characterized by unevenness during the year. Seasonality is especially evident when the failures are analysed at particular times of the year. The main purpose of this paper is to present the problems of failures in water supply network caused by seasonal changes, to determine seasonal indicators and to give an example of the system failure analysis for the selected city of south-eastern Poland. The analysis was based on actual operational data obtained from water supply company.
Determining the NOx emission from an auxiliary marine engine based on its operating conditions
Authors: Rymaniak Lukasz , Pielecha Jacek , Brzeziński Lukasz
Published: July 2018

The article presents considerations regarding determining the NOx emissions from auxiliary compression-ignition marine engines. In order to determine the real impact of a given object on air pollution, it is necessary to first carry out research aimed at determining its emission characteristics. Thus, it is necessary to conduct tests in real operating conditions or to calculate the ecological indicators based on the operating conditions. The paper presents the NOx emissions intensity of an auxiliary Tier III standard marine engine, which is used in the drive system of various heavy, off-road vehicles and water vessels. Due to the structure characteristics of the considered engine group, the presented relations and results refer to only one cylinder. This data was used to calculate the NOx emission of a marine auxiliary engine, which used the operating conditions obtained from dynamometer tests and the engine construction (the number of cylinders). The presented methodology of activities can be used to assess the ecological indicators of ships in actual navigation, including primarily the maneuvers performed in the port. The article is supplemented with theoretical considerations regarding the problem of pollutant emissions from auxiliary marine engines.
Experimental investigation of the kinetic energy correction factor in pipe flow
Authors: Janusz Teleszewski Tomasz
Published: July 2018

In this study, an experimental investigation of the kinetic energy (Coriolis) correction factor in laminar, transitional and turbulent flow in a transparent smooth pipe with a Reynolds number up to 25000 is performed. The velocity profiles are obtained using a laser Doppler velocimetry (LDV). Based on the experimental results obtained for Re < 25000, generalized correlations for the kinetic energy correction factor as a function of the Reynolds number are presented. The results of the research are compared with experimental results reported by other authors. The predicted correlations for the kinetic energy correction factor can be a very useful resource for the hydraulic calculations of fluid through circular ducts.
Method of Ear Detection for Maize Seed Based on Fisher Criterion
Authors: Kang Zhiqiang , Yuan Chaohui , Cheng Ruifeng
Published: July 2018

The purpose of this paper is to use machine vision to detect the size, shape, texture and color of maize seed ear. The traditional method is very limited and cannot meet the detection efficiency. This paper used logistic regression linear discriminant analysis method, the rule of perceptron, Fisher method and the least-square method, this paper use change between the Fisher criterion according to the the class of discrete degree error matrix and matrix of the discrete degree of reconstruction error in class than the maximum projection direction, classifying clusters. By fusion Fisher discriminant analysis method for testing in the test, through a large number of experiments and comparison method, the experiment proved that Fisher can high efficiency and high precision of classifying seed corn ear detection.
Wenn das Herz Hilfe braucht
Authors: Schäfer Sabine
Published: July 2018

Aktuelle Daten zeigen, dass weltweit etwa 50 Millionen Menschen an einer fortgeschrittenen, terminalen Herzinsuffizienz leiden und jährlich etwa zwei Millionen
Neuerkrankungen dazukommen. Die letzte Option für Patienten, bei denen weder die konventionelle noch die operative Therapie eine Besserung herbeiführen konnte,
ist die Transplantation oder die mechanische Kreislaufunterstützung. Infolge des Rückgangs der Spenderorgane und im Zuge der Entwicklung bei den ventrikulären
Unterstützungssystemen steigen seit den 1990er-Jahren die Implantationszahlen von Herzunterstützungssystemen deutlich an. 1
Dieser Beitrag gibt einen Überblick über die Entwicklung der ventrikulären Unterstützungssysteme sowie über Indikationen, Komplikationen und Nachsorge – mit
Schwerpunkt auf die gängigsten und meistverwendeten Modelle.
Pflegeexpertin APN als Schlüsselrolle im Delirmanagement
Authors: Moser Andrea , Fröhlich Martin R. , Suter-Riederer Susanne
Published: July 2018

Delirante Patienten in komplexen Situationen pflegen, verunsicherte Angehörige begleiten und das interprofessionelle Behandlungsteam unterstützen – die Advanced
Practice Nurse (APN) kann eine Schlüsselrolle im Delirmanagement auf Intensivstationen einnehmen. Ein delirspezifisches APN-Modell bildet ihre Tätigkeiten ab
und weist auf innovative Formen der Zusammenarbeit hin.
Das Jahr der Jubiläen
Authors: Schäfer P. Klaus
Published: July 2018

Das Jahr 2017 ist verstrichen, ohne dass in größerem Maße der Jubiläen zu Hirntod und Organtransplantation gedacht wurde. Aber auch für 2018 stehen große Jubiläen an. Wir betrachten die Jubiläen beider Jahre.
Die Rechtsfrage: – Wie kann ich neben dem Studium als Therapeutin arbeiten?
Authors: Bossow Karsten
Published: July 2018

„Ich bin Therapeutin und möchte nun neben meinem Masterstudium weiterhin meine Patienten betreuen. Welche Möglichkeiten habe ich?“

Alessa S. aus Düsseldorf
The Current S2e Guideline for Hallux valgus – Evidence-based Guideline Development Using Meta-analysis
Authors: Waizy Hazibullah , Panahi Babak , Dohle Jörn , Stukenborg-Colsman Christina
Published: July 2018

Die Hallux-valgus-Fehlstellung ist unbehandelt meist als progrediente Deformität anzusehen. Sie führt jedoch nicht zwangsläufig zu Schmerzen und Leidensdruck bei den Patienten. Prävention primär: Fußgerechtes Schuhwerk sowohl zur Vermeidung von Druckstellen als auch zur Vermeidung einer forcierten Progredienz der Pathologie. Funktionelle Stabilisierung des Fußes mittels Gymnastik oder physiotherapeutischer Anleitung. Prävention sekundär: Orthesenversorgung und/oder Einlagenversorgung zur Verbesserung der funktionellen Stabilisierung. Prävention tertiär: Die konsequente adaptierte postoperative Nachbehandlung, die sich an den operativen Maßnahmen orientiert. Die Indikation zur Einleitung einer therapeutischen Maßnahme beim Hallux valgus ist abhängig vom Leidensdruck des Patienten, Alter und Vorliegen einer Arthrose im Großzehengrundgelenk. Weitere patientenspezifische Pathologien können die Einleitung einer Therapie ebenfalls beeinflussen. In der 1. Stufe der ambulanten Therapie stehen die Beratung und Physiotherapie im Vordergrund, additiv Analgetika oder antiphlogistische Maßnahmen. Manuelle Therapien, physiotherapeutische Maßnahmen, Orthesen oder orthopädietechnische Maßnahmen sind in Anbetracht der bestehenden Pathologie und des Leidensdruckes anzuwenden. In der Stufe 2 der ambulanten bzw. stationären therapeutischen Maßnahmen ist beim symptomatischen Hallux valgus die operative Therapie indiziert. Die operative Therapie sollte sich dabei sowohl am Schweregrad der Pathologie als auch an den postoperativen Mobilisationsmöglichkeiten des Patienten und weiteren patientenspezifischen Kriterien orientieren.
„Reha vor Pflege“ – zur Problematik einer undeutlichen gesundheitspolitischen Regelstrategie – ein Positionspapier
Authors: Zerth Jürgen , Wasem Jürgen , Matusiewicz David
Published: July 2018

Das Prinzip „Reha vor Pflege“ lässt sich als Schwesterprinzip zu „ambulant vor stationär“ verstehen. Gleichwohl weisen die Zahlen aus den Routinedaten als auch
die Erfahrungen der Akteure darauf hin, dass das Prinzip nur unzureichend umgesetzt wird. Diese Frage aufgreifend hat sich ein interdisziplinärer Autorenkreis
zusammengetan, um auszuloten, welche Bedeutung in der realen Versorgung das Prinzip „Reha vor Pflege“ haben kann und welche Implikationen für eine
gesundheitspolitische Weiterentwicklung daraus abzuleiten wären. Diese Ergebnisse dieses Workshops sind im nachfolgenden Papier dargelegt.
Fall für Vier – Intensivtherapie
Authors: Hägele Anke
Published: July 2018

Der dreijährige Jannik hat eine unilaterale spastische Zerebralparese. Neben ambulanter Therapie bekam er die Chance einer stationären Therapie in einer spezialisierten Düsseldorfer Klinik. Sein Arzt, seine Ergo- und Physio-therapeutin und seine Motopädin schildern, wie sie den Jungen in dieser Zeit therapiert haben.
Ex-Vivo and In-Vitro Evidence that Low Molecular Weight Heparins Exhibit Less Binding to Plasma Proteins than Unfractionated Heparin
Authors: Young Edward , Wells Philip , Holloway Scott , Weitz Jeffrey , Hirsh Jack
Published: July 2018

We have compared the non-specific binding of unfractionated heparin (UFH) with that of low molecular weight heparin (LMWFl) to plasma proteins both ex vivo and in vitro. Non specific binding to plas ma proteins was assessed by comparing the heparin levels measured as anti-factor Xa activity before and after the addition of low affinity heparin, which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. For the ex-vivo studies, we compared the recovery of UFH and a LMWH (ardeparin) from the plasma of patients participating in a randomized trial of post operative venous thrombosis prophylaxis. For the in-vitro studies, we compared the recovery of UFH and 4 different LMWHs when added to the plasma from healthy volunteers and from patients with suspected venous thromboembolic disease. The results indicate that the recovery of LMWH is much less affected by nonspecific binding to plasma proteins both ex-vivo and in-vitro. In addition, there are differences between the LMWHs with respect to their plasma protein-binding.
Rabbit Plasma, unlike Its Human Counterpart, Contains no Complex between Protein S and C4b-Binding Protein
Authors: He Xuhua , Dahlbäck Björn
Published: July 2018

In human plasma, the anticoagulant vitamin K-dependent protein S exists in two molecular forms, as free protein and complexed to C4b- binding protein (C4BP), a complement regulatory protein. It has been suggested that rabbit plasma also contains two forms of protein S and that the interaction between protein S and C4BP m rabbits can be modulated by synthetic peptides corresponding to a sequence (residues 605-614) in the carboxy-lerminal part of protein S. In this report, we provide itsulls which challenge the conclusion that rabbit plasma contains the complexed form of protein S. The two forms of protein S in human plasma were separated by gel filtration chromatography on Sephacryl S-300 and the presence of protein S in the various fractions analyzed by Western blotting using a monoclonal antibody (HPS 21) directed against the γ-carboxyglutamic acid rich module of human protein S. This antibody, which was found to cross-react with rabbit protein S on Western blotting, was used in affinity purification of protein S from rabbit plasma as well as of recombinant rabbit protein S. HPS 21 specifically recognized protein S in rabbit plasma and did not cross-react with the other vitamin K-depeudenl plasma proteins. To elucidate whether rabbit plasma contained two forms of protein S, rabbit plasma was subjected to gelfiltration chromatography followed by Western blotting of the fractions with monoclonal antibody HPS 21. Protein S was found only in fractions eluting at a position corresponding to that of free protein S. A radiolabelled trace amount of recombinant rabbit protein S added to rabbit plasma chromatographed as free protein S and no high molecular weight form corresponding to a C4BP-protein S complex was detected. Rabbit protein S had the capacity to bind human C4BP and the addition of human C4BP to rabbit plasma changed the elution profile, of rabbit plasma protein S. After the addition of human C4BP, rabbit plasma protein S quantitatively eluted as a high molecular weight complex, suggesting that all the protein S in rabbit plasma was bound to human C4BP. The anticoagulant activity of human protein S is modulated by the complex formation with C4BP. Our results demonstrate that this function of C4BP and the protein S-C4BP complex formation has not been conserved throughout the evolution even though protein S has a preserved C4BP binding site.
Phospholipid-Specific Conformational Changes in Human Prothrombin upon Binding to Procoagulant Acidic Lipid Membranes
Authors: Wu Jogin R , Lentz Barry R
Published: July 2018

This paper provides evidence to demonstrate that human prothrombin undergoes conformational changes upon binding to procoagulant membranes specifically containing phosphatidylserine (PS). Fourier transform infrared spectroscopy was used to show a slight increase in ordered (α-helix, β-sheet, β-turns) secondary structure upon binding to PS-containing membranes. Thermograms representing prothrombin and prothrombin fragment 1 denaturation were obtained using differential scanning calorimetry. These were analyzed and interpreted in terms of changes in prothrombin domain organization associated with binding to PS-containing membranes. Changes in either secondary structure or domain organization upon binding to negatively-charged phosphatidylglycerol-containing membranes were, if they occurred at all, much less dramatic. The results paralleled results obtained previously with bovine prothrombin (1, 2). The implications of these results in terms of a possible molecular mechanism for the cofactor-like role of platelet membrane vesicles in prothrombin activation are discussed.
Scanning Electron Microscopic and Electrophoretic Studies on Clotting Factor Adsorbents
Authors: Deacon S. L. M , Howell R. M
Published: July 2018

Physical studies carried out on a range of protein and clotting factor adsorbents revealed marked morphological and charge differences. Their appearance in the scanning electron microscope could be used to classify the insoluble precipitates, calcium phosphate, barium sulphate and citrate, as either amorphorous or crystalline.

Surface charge is difficult to define but the present studies on the sparingly-soluble salts, based on calcium and barium, have revealed that they can be subdivided on the basis of the presence or absence of a charge reversal point in the pH-mobility curve. The anion component appeared to determine this characteristic; it was noted that phosphate and citrate ions had a marked effect and gave a biased negative potential at all pH values. We concluded that where a divalent cation is cohabiting with a trivalent anion, the greater potential-determining ability of the latter will dominate the overall charge at the surface of a particle, even below pH7 and the absence of a positive potential gives a monophasic pH-mobility curve.

Differences in both the physical appearance and electrophoretic mobility of the adsorbents studied reflect the wide variation in their chemical composition, especially among the various forms of calcium phosphate which, unlike barium sulphate, can include substituted ions such as hydroxyl, in their crystal lattice. The definition of these characteristics allows their behaviour towards clotting factors to be more easily predicted.
Effects of Fasting on Plasma and Platelet-Free Fatty Acids and Platelet Function in Healthy Males
Authors: Gjesdal Knut , Nordøy Arne , Wang Harald , Berntsen Harald , Mjøs Ole D.
Published: July 2018

10 healthy male volunteers fasted for 72 hours. Their plasma concentration of free fatty acid increased more than two-fold, to 1.8 mmol/1. The number of reversible venous “in vivo” platelet aggregates increased significantly (p <0.01); this figure correlated with the concentration of long-chain saturated free fatty acid in plasma (p <0.02). The correlation with the amount of long-chain saturated free fatty acid plus oleic acid (18:1) was even better (p <0.01). Plasma PF-4 concentration increased, suggesting increased platelet release reaction. In spite of the plasma increase, total platelet FFA concentration was reduced and there was a change in the distribution of platelet free fatty acid which correlated with the degree of aggregation.
Prevention of Deep Vein Thrombosis after Major Knee Surgery - A Randomized, Double-Blind Trial Comparing a Low Molecular Weight Heparin Fragment (Enoxaparin) to Placebo
Authors: Leclerc Jacques R , Geerts William H , Desjardins Louis , Jobin François , Laroche François , Delorme Fernand , Haviernick Sylvie , Atkinson Susan , Bourgouine Jean
Published: July 2018

Consecutive patients undergoing knee arthroplasty or tibial osteotomy at four participating hospitals received either enoxaparin, 30 mg subcutaneously every 12 h (n = 66) or an identicalappearing placebo (n = 65). All study medications started the morning after the operation and were continued up to a maximum of 14 days. Patients underwent surveillance with 125I-fibrinogen leg scanning and impedance plethysmography. Bilateral contrast venography was performed routinely at Day 14 or at time of discharge, if sooner. Deep vein thrombosis was detected by venography in 35 of 54 patients (65%) in the placebo group and in 8 of 41 patients in the enoxaparin group (19%), a risk reduction of 71%, P <0.0001. For the entire study group, deep vein thrombosis was detected by either venography of non-invasive tests in 37 of 64 patients (58%) in the placebo group and in 11 of 65 patients (17%) in the enoxaparin group, a risk reduction of 71%, P <0.0001. Proximal vein thrombosis was found in 19% of the placebo patients and in none of the enoxaparin patients, a risk reduction of 100%, P <0.001. Bleeding complications occurred in 5 of 65 patients (8%) in the placebo group and in 4 of 66 patients (6%) in the enoxaparin group, P = 0.71. There were no differences in the amount of blood loss, minimum hemoglobin levels and number of units of packed red cells given between the two treatment groups. We conclude that a fixed dose regimen of enoxaparin, started post-operatively, is an effective and safe regimen for reducing the frequency of deep vein thrombosis after major knee surgery.
Lupus Anticoagulant Activity Is Frequently Dependent on the Presence of β2-Glycoprotein I
Authors: Oostin Janine D , Derksen Ronald H W M , Entjes H Tanja I , Bouma Bonno N , de Groot Philip G
Published: July 2018

Antiphospholipid antibodies (aPL) are defined by anticardioli-pin antibody (aCL) ELISA and prolongation of phospholipid dependent coagulation assays (lupus anticoagulant; LAC). For the binding of aCL to cardiolipin a cofactor, β2-glycoprotein I (β2-GPI), is necessary. We have investigated whether the same cofactor is essential for LAC activity. Plasma from 6 LAC positive patients and 3 controls was depleted from β2-GPI by means of affinity chromatography. From the 6 LAC positive plasmas, 4 became LAC negative (tested with dRWT) when β2-GPI was depleted and became positive again when purified β2-GPI (200 μg/ml) was added. A dose response curve showed that addition of 50 μg/ml β2-GPI to β2-GPI deficient patient plasma, led to a positive dRWT. Depletion of, and addition of β2-GPI to plasma from controls had no effect on the dRWT. Measurement of β2-GPI plasma levels in 19 LAC positive patients, 40 LAC negative patients and 15 controls showed no difference in β2-GPI levels.

These results show that a combination of aPL and β2-GPI is essential not only for binding to cardiolipin, but also for LAC activity and imply that low β2-GPI levels (<50 μg/ml) can lead to false negative LAC tests. These observations may lead to new insights in the pathophysiological complications associated with aPL.
A Randomized and Blinded Comparison of Three Bleeding Time Techniques: the Ivy Method, and the Simplate II® Method in Two Directions
Authors: Šrámek R , Šrámek A , Koster T , Briët E , Rosendaat F R
Published: July 2018

We compared the Ivy bleeding time method and two alternatives of the Simplate II® method (incisions in horizontal and vertical direction) with each other, with regard to the sensitivity, the specificity, the costs and the burden for the patient. In the aspirin study an aspirin-induced bleeding defect was used. Seventy-two healthy volunteers were randomized to receive either 500 mg acetylsalicylic acid (ASA) or a placebo. Double blinding was maintained throughout the study. In the anticoagulation study 62 patients participated, who received oral anticoagulants (OAC) for various reasons. All participants received two bleeding time methods. The burden for the participants of each method was screened by a small standard questionnaire.

The differences in sensitivity and specificity between the three methods proved minimal. The Ivy method was more often preferred by the participants than the Simplate methods.

Since a choice on the basis of sensitivity and specificity appears not possible, we prefer the Ivy method because of lower costs and less burden.
Value of Liquid Crystal Contact Thermography and Plasma Level of D-Dimer for Screening of Deep Venous Thrombosis Following General Abdominal Surgery
Authors: Bounameaux H , Khabiri E , Huber O , Schneider P-A , Didier D , Moerloose P de , Reber G
Published: July 2018

Because the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular-weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 pg/1, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 pg/1 for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%.

Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 pg/1) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography. This sequential approach might be useful in studies of the efficacy of antithrombotic regimens for prophylaxis of DVT in patients at risk.
Release of Thromboxane A2 and β-Thromboglobulin during In-Vivo Plug Formation following Standardized Skin Incisions: Effect of a Moderate Fish Intake
Authors: Houwelingen Adriana C v , Thorngren Margareta , Hornstra Gerard , Born Gustav V R
Published: July 2018

This paper describes a controlled study of the effects of a fish supplement on haemostasis. This was evaluated by measuring bleeding times from skin incisions, the volume of the emerging blood, the number of platelets taking part in the formation of the haemostatic plug (platelet retention), and the release of thromboxane B2 and β-thromboglobulin in volunteers, before and after consuming a daily supplement of 100 g of fish (n = 20) or meat (n = 20) paste for 6 weeks. The fish supplement decreased the amount of thromboxane B2 released per platelet incorporated into the plug. Despite this, the skin bleeding times were hardly changed. There was also no difference in platelet retention, which was consistent with there being no difference in the release of β-thromboglobulin.

These results suggest that in the effect of marine diets on haemostasis, a reduced vascular reactivity plays a more important role than decreased plug formation.
Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment
Authors: Nurmohamed Michael T , Berckmans René J , Morriën-Salomons Willy M , Berends Fenny , Hommes Daan W , Rijnierse Joep J M M , Sturk Augueste
Published: July 2018

Background. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.

Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.

Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.

Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.
Expression of Platelet Membrane Glycoprotein V in Human Megakaryocytes and Megakaryocytic Cell Lines: A Study Using a Novel Monoclonal Antibody against GPV
Authors: Takafuta Toshiro , Fujirmura Kingo , Kawano Hironori , Noda Masaaki , Fujimoto Tetsuro , Oda Kenji , Shimomura Takeshi , Kuramoto Atsushi
Published: July 2018

Glycoprotein V (GPV) is a platelet membrane protein with a molecular weight of 82 kD, and one of the leucine rich glycoproteins (LRG). By reverse transcription-polymerase chain reaction (RT-PCR), GPV cDNA was amplified from mRNA of platelets and megakaryocytic cell lines. However, since there are few reports indicating whether GPV protein is expressed in megakaryocytes as a lineage and maturation specific protein, we studied the GPV expression at the protein level by using a novel monoclonal antibody (1D9) recognizing GPV. Flow cytometric and immunohistochemical analysis indicated that GPV was detected on the surface and in the cytoplasm of only the megakaryocytes in bone marrow aspirates. In a megakaryocytic cell line UT-7, GPV antigen increased after treatment with phorbol-12-myri-state-13-acetate (PMA). These data indicate that only megakaryocytes specifically express the GPV protein among hematopoietic cells and that the expression of GPV increases with differentiation of the megakaryocyte as GPIb-IX complex.
A Single Base Pair Deletion in the Promoter Region of the Factor IX Gene Is Associated with Haemophilia B
Authors: Hall Adrian J , Chuansumrit Ampaiwan , Peake Ian R , Winship Peter R
Published: July 2018

Patients with the haemophilia B Leyden phenotype show a distinct pattern of factor IX expression characterized by a post-pubertal increase in FIX levels and the remission of clinical symptoms in adult life. This phenotype has previously been linked to single base mutations within transcription factor binding sites in a region of ∼40 bp around the major start point of transcription of the FIX gene. Here we report a novel mutation in this region within the transcription factor C/EBP binding site at +1 to +18. The mutation is a single base pair deletion from a triplet of thymine residues at +6 to +8. We show that the extent to which this mutation disrupts the binding of C/EBP to its binding site is less marked than the disruption caused by the +13 A→G mutation of FIX Norwich (1). This correlates with age-matched phenotypic data we have available for the patient reported here and that of FIX Norwich.
Recombinant Versus High-sensitivity Conventional Thromboplastin: A Randomized Clinical Study in Patients on Oral Anticoagulation
Authors: Finazzi Guido , Falanga Anna , Galli Monica , Cortelazzo Sergio , Remuzzi Andrea , Barbui Tiziano
Published: July 2018

A prospective, randomized, double-blind clinical trial was carried out in a single center to compare the clinical and laboratory quality of oral anticoagulant therapy monitored with recombinant tissue factor (RTF) or with a sensitive, human-derived, conventional thromboplastin (CT) in the PT test. Seven hundred and fifty-seven consecutive patients receiving oral anticoagulation for various indications were randomized to RTF (n = 379) or CT (n = 368) for 6 months. Total follow-up was 167 and 153 patient-years for RTF and TP groups respectively. Fifty-six bleeding events were observed: 31 in the RTF group and 25 in the TP group. The incidence of bleeding was 18.5 and 16.5% pt-yrs for RTF and TP patients respectively (n.s.). The event-free follow-up curves were not significantly different between the two groups. The laboratory quality of oral anticoagulation was evaluated with the “last check in file” method: therapeutic INR was found in the same propor-tipn of RTF and TP patients (70.2% vs 68.8%). Our study shows that RTF is as effective as a sensitive, conventional thromboplastin for monitoring oral anticoagulation.
Recombinant Variants of Tissue-type Plasminogen Activator Containing Amino Acid Substitutions in the Fibronectin Finger-like Domain and the Kringle 1 Domain
Authors: Yahara Hitoshi , Matsumoto Keiji , Maruyama Hiroyuki , Nagaoka Tetsuya , Ikenaka Yasuhiro , Yajima Kazuyoshi , Fukao Hideharu , Ueshima Shigeru , Matsuo Osamu
Published: July 2018

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which is used to treat acute myocardial infarction. Pharmacokinetic-ally, t-PA is characterized by a rapid clearance from the circulation. In a previous study, we constructed variant forms of t-PA with genetic modifications at the fibronectin finger-like domain (finger domain) or at the kringle 1 domain (K1 domain). The finger modified variant, t-PA N37S.S38V.G39V.R40E. A41F.Q42S had about a 6.0-fold higher plasma half-life in vivo than wild-type t-PA. Two variants with modifications in the K1 domain, t-PA G161R.K162R.S165W and t-PA N115P, showed an improved kinetic parameters and a 2.2-fold higher plasma half-life in vivo than wild-type t-PA, respectively. To create a recombinant variant of t-PA with a higher enzymatic activity and a further prolonged half-life in vivo, the genes containing each modifications were joined and expressed in animal cells. The two variants, t-PA N37S.S38V G39V.R40E.A41F.Q42S.G161R.K162R.S165W and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N 115P, were purified from conditioned media and their biochemical, pharmacokinetic and thrombolytic profiles were investigated. Although the variant t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G161R.K162R.S165W demonstrated an impaired enzymatic activity compared to the wild:type t-PA, the half-life of the variant, t-PA N37S.S38V.G39V.R40E.A41F.Q42S. N115P, following intravenous bolus injection in rabbits was considerably longer than that of finger-domain modified variants. Human plasma clot lysis assay estimated the fibrinolytic activity of both variants to be about 2.0-fold less effective than that of the wild-type t-PA. In the rabbit jugular vein clot lysis model, doses of 1.0 and 0.0625 mg/kg were required for about 70% lysis in the wild-type t-PA and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N115P, respectively. These findings suggested that the variant in this study can be used at a lower dosage in a single bolus injection.
Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta
Authors: Gjesdal Knut , Pepper Duncan S.
Published: July 2018

Human platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.
Effects of t-AMCHA and EACA on the Plasma Kallikrein System
Authors: Nakahara Masao
Published: July 2018

Varied amounts of t-AMCHA or EACA added to non-contact fresh dog plasma generates kininogenase and TAME esterase activities. These phenomena may be abolished by prior addition of lima bean trypsin inhibitor. t-AMCHA or EACA had no effect on partially purified kallikrein, but had a significant inhibitory influence on plasma kininase. The generation of prekallikrein activator with t-AMCHA was ascertained by gel filtration on a Sephadex G-100 column. The blood kinin level increased about 50% one hr after administration of t-AMCHA. It is suggested from these results that t-AMCHA may initiate the true activation of the kallikrein system by activating the Hageman factor.
Heparin Therapy during Cardiopulmonary Bypass in Children Requires Ongoing Quality Control
Authors: Andrew Maureen , MacIntyre Brian , MacMillan James , Williams William G , Gruenwald Colleen , Johnston Marilyn , Burrows Fred , Wang Elaine , Adams Margaret
Published: July 2018

Heparin therapy for children undergoing cardiopulmonary bypass (CPB) is monitored in the operating room by automated whole blood activated clotting times (ACT). For many years our institution used Hemochron (HC) ACT machines but changed to HemoTec (HT) ACT machines because they required a smaller blood sample and provided results in duplicate. When HemoTec ACT machines were introduced at our institution, the surgical team was concerned that increased amounts of heparin were being administered to our patients during CPB. This study was conducted to investigate the potential mechanisms responsible for these clinical observations. First, we compared ACT values on ex vivo blood samples from 20 consecutive pediatric patients (6 samples each) during CPB. The HC ACT values were significantly and systematically increased over HT ACT values (HC: 750 ± 40 vs HT: 418 ± 26, Mean ± SEM, p <0.01). 94% of all HC ACT values were above 450 s compared to only 27% of HT ACT values. If HT ACT values had been used for patient monitoring, all patients would have received more heparin to achieve ACT values above 450 s. The two machines reported similar ACT values when heparin was added in vitro to whole blood (0.1-5.0 units/ml), (HC: Y = 98X + 104, r2 = 0.93 HT: Y = 82X + 109, r2 = 0.94). Heparin concentrations in our patients following a bolus of 300 U/kg of heparin, but prior to CPB were 3.2 ± 0.07 units/ml. Following the initiation of CPB, heparin concentrations decreased to 1.3 ± 0.05, reflecting, in part, hemodilution by the pump prime (1 U of heparin/ml). In contrast to the in vitro results, there was no relationship between ACT values measured by either machine and plasma heparin concentrations in ex vivo samples. Finally, plasma concentrations of 8 coagulation proteins measured prior to CPB and following CPB were decreased by 27-55%, predominantly reflecting the final dilution by CPB. In conclusion: 1) HT and HC machines cannot be used interchangeably in pediatric patients without risk of altering clinical practice in an uncontrolled fashion; and 2) ACT values from children on CPB correlate poorly with heparin concentrations, likely due to hemodilution. Optimal use of anticoagulant therapy during CPB in children requires further study in clinical trials and ongoing quality control.
Effect of Isotretinoin on Endogenous Tissue-Type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor 1 (PAI-1) in Humans
Authors: Wallnöfer A E , van Griensven J M T , Schoemaker H C , Cohen A F , Lambert W , Kluft C , Meijer P , Kooistra T
Published: July 2018

The effect of isotretinoin on fibrinolysis was investigated in 10 healthy, male volunteers in a randomized, double-blind, crossover-designed study. Isotretinoin (40 mg) was administered in the morning and in the evening for 5 days. t-PA, u-PA and PAI-1 antigen and activity in plasma were measured every morning at 9 a.m. on days 1 to 4 and every 3 hours over 24 hours on day 5. Isotretinoin treatment had no significant stimulatory effect on endogenous t-PA antigen and activity in morning plasma samples nor on their circadian variation. Also, u-PA antigen levels did not change after isotretinoin treatment. Mean PAI-1 antigen and PAI activity in 9 a.m. plasma samples were non-significantly higher during isotretinoin than during placebo treatment. After treatment with isotretinoin a significant rise of fasting triglyceride plasma levels was observed as compared to placebo. The study shows that isotretinoin has no clinically significant effect on endogenous fibrinolysis.
Demonstration of Rickettsia Conorii-Induced Coagulative and Platelet Activation in vivo in Patients with Mediterranean Spotted Fever
Authors: Davì Giovanni , Giammarresi Carlo , Vigneri Sergio , Ganci Antonina , Ferri Claudio , Di Francesco Letizia , Vitale Giustina , Mansueto Serafino
Published: July 2018

Endothelial injury in vivo induced by Rickettsia Conorii, the etiologic agent of Mediterranean Spotted Fever (MSF) has been recently demonstrated. We sought to determine whether platelet and/or coagulative activation in vivo can be demonstrated in the acute phase of MSF, through measurements of a major metabolite of thromboxane (TX) in the urine (1 1-dehydro-TXB2) and of plasma prothrombin fragment 1+2, whose levels reflect activation of prothrombin to thrombin. Moreover, we measured plasma endothelin-1 as marker of endothelial dysfunction. Our results provide biochemical evidence for the occurrence of TXA2-dependent platelet activation and thrombin generation in vivo, together with endothelial dysfunction. These phenomena could account for clinical manifestations of MSF, such as vasculitis and focal microthrombus formation. These results could also provide a rationale for testing the efficacy of aspirin or heparin in reducing the prothrombotic status of Rickettsiae diseases.
Primary Prevention of Coronary Arterial Thrombosis with the Factor Xa Inhibitor rTAP in a Canine Electrolytic Injury Model
Authors: Lynch Joseph J , Sitko Gary R , Lehman E Dale , Vlasuk George P
Published: July 2018

The antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex (LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls), rTAP (50 μg/kg/min continuous infusion) or heparin (200 U/kg bolus followed by 2 U/kg/min continuous infusion) were started 60 min prior to the initiation of LCX coronary artery electrolytic injury (150 μA continuous anodal current). All 6/6 saline-treated control animals developed occlusive thrombi at 49.8 ± 13.6 min after the initiation of vessel injury, and possessed a residual thrombus mass of 20.7 ± 3.3 mg. In the rTAP treatment group, 4/6 preparations developed occlusive thrombi, but with times to thrombosis delayed significantly compared to both the saline control as well as to the heparin treatment group (202.7 ± 28.9 min; p <0.01 to both saline and heparin groups). The remaining 2 rTAP-treated preparations remained patent despite the continued electrical stimulation of the coronary vessel for 5 h. Residual thrombus mass in the rTAP treatment group was reduced markedly compared to the saline control group (4.4 ± 1.0 mg; p <0.01). Heparin infusion resulted in a modest but statistically insignificant delay in occlusive LCX coronary artery thrombosis compared to saline controls, with all 6/6 heparin-treated preparations occluding at 79.7 ± 16.5 min after the initiation of vessel injury. Residual thrombus mass in heparin-treated animals, however, was reduced compared to saline controls (9.4 ± 1.4 mg; p <0.01). These results support a pivotal role for fXa in the process of arterial thrombosis, as well as the feasibility of inhibiting fXa as an effective strategy for the primary prevention of arterial thrombosis.