bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of inflow velocity on thermal stratification in a water storage tank
Authors: Kozłowska Kamila , Jadwiszczak Piotr
Published: July 2018

The paper presents the analysis of thermal processes occurring in thermal energy storage tanks used for heating hot water systems. Three-dimensional Computational Fluid Dynamics (CFD) methods were used. The standard buffer charging stage was modelled for three tank inlets’ diameters DN20, DN40 and DN80. With a constant charging water flow and temperature the port diameter affects inlet velocity, heat storage dynamics, thermal stratification and thermocline thickness in storage tank. The smallest diameter causes unfavourable thermal mixing of accumulated water, and the largest diameter supports thermal stratification
Post-treatment of coke wastewater on activated carbons
Authors: Kwarciak-Kozłowska Anna , Madeła Magdalena , Wrońska Magdalena
Published: July 2018

The aim of this research was to determine the effect the ozonation and sonification processes for post-treatment of coke wastewaters using activated carbons. The tests were carried out in three systems ie. I-AC (activated carbon), II-O3+AC (ozonation + activated carbon) and III-US+AC (ultrasound + activated carbon). In the experiment were used a three types of activated carbons: WG-12, ROW 08 Supra and Picabiol. The sorption process was carried out in static conditions at contact for 24h time of the wastewater with activated carbons. Coke wastewater was oxidized through ozonation at a constant ozone dose of 10 mg/dm3. Sonication of coke wastewater was conducted at vibration amplitude was 61.5 μm, with sonication time of 8 min. Results of removing of COD were estimated on the base of sorption capacity and COD removal efficiency. The second system was the most effective (O3+AC) for carbons WG-12 and ROW 08 Supra, whereas in the case of carbon Picabiol, the best efficiency was found for system I (AC). The lowest efficiency of removal of COD from coke wastewater was the systems III (US+AC) for all three activated carbons.
Impact of stirrer rotational speed on liquid circulation in a rectangular vessel – a study applying DPIV
Authors: Ligus Grzegorz , Wasilewski Marek
Published: July 2018

This paper contains the results of experimental study concerned with liquid mixing process using a stirrer located in a rectangular vessel. The current study applied Digital Particle Image Velocimetry technique (DPIV). On the basis of non-invasive measurements, velocity vector profiles were determined with regard to the velocity of the mixing process, and they were subsequently applied for identification and assessment of liquid circulation in a vessel. The correlation between the rotational speed of the stirrer and fluctuations and directions of the liquid flow velocity were determined. This paper focuses on the assessment of the mixing intensity resulting from the rectangular geometry of the vessel. The study proposes and develops a dependence between the shape of the velocity profile of the circulating liquid and the intensity of the mixing process. The study demonstrates the existence of suitable conditions for performing mixing processes in rectangular vessels.
Polymer materials with controlled degradation time
Authors: Niedzielska Ewelina , Masek Anna
Published: July 2018

The aim of this work was carry out accelarated process of ageing for cyclic olefin copolymer ethylene – norbornene (Topas). The Topas cyclic olefin copolymer (COC) family characterize high transparency, excellent mechanical properties and low water permeability. The influence of external factors such as UV radiation, elevated temperature, oxygen effect and humidity causing degradation of polymer macroparticles was also investigated. The properties of the polymer before and after weathering and UV radiation were also compared. Degradability was examinated by measuring color change, FTIR spectrum analysis and determination of the ageing factor k. The tensile strength, elongation at break and hardness of composites by Shore A method were measured. The synergistic effect of temperature, humidity and UV radiation reduces the mechanical properties of the samples tested, while the interaction of only UV radiation on the samples causes a significant change color.
Application of NGS for studying the antibiotic resistant microbiome in Wrocław tap water
Authors: Siedlecka Agata , Piekarska Katarzyna
Published: July 2018

The NGS method was used to investigate the biodiversity of ARB dwelling in tap water, able to form biofilm on bullion media supplemented with antibiotics: β-lactam, fluoroquinolone, 3rd generation cephalosporin and tetracycline. Biofilms formed by cold-and hot-tap water microorganisms were also examined. The presence of 10 ARGs in plasmid DNA of cultivated biomass was tested using a standard PCR. The analyses revealed that the most predominant families were Sphingomonadaceae, Paenibacillaceae, Enterobacteriaceae, Bacillaceae and Sphingomonadaceae in FQ, C3G, T, C-W and H-W samples, respectively (explanations of abbreviations in the text). The ARGs did not correlate with resistance phenotypes.
Assessment of thermal comfort in lecture room by chosen calculation methods
Authors: Wesołowska Małgorzata , Laska Marta
Published: July 2018

The proper level of comfort conditions is one of the main goal when designing HVAC systems in buildings. It influences our self-being, our health and productivity. Thermal comfort is a complex issue and relates to indoor air parameters and personal factors. The publication presents the outcome of the research undertaken in one of the lecture room at Wroclaw University of Science and Technology, Poland. It consisted of measurements of comfort parameters, questionnaire survey and PMV and PPD calculations based on different approaches.
Cryogenic energy storage system coupled with packed-bed cold storage
Authors: Wojcieszak Paweł , Malecha Ziemowit
Published: July 2018

Cryogenic Energy Storage (CES) systems are able to improve the stability of electrical grids with large shares of intermittent power plants. In CES systems, excess electrical energy can be used in the liquefaction of cryogenic fluids, which may be stored in large cryogenic vessels for long periods of time. When the demand for electricity is high, work is recovered from the cryogen during a power cycle using ambient or waste heat as an upper heat source. Most research is focused on liquid air energy storage (LAES). However, natural gas can also be a promising working fluid for the CES system. This paper presents a natural gas-based CES system, coupled with a low temperature packed bed cold storage unit. The cold, which is stored at a low temperature level, can be used to increase the efficiency of the cryogenic liquefiers. The model for the packed bed in a high grade cold storage unit was implemented and then compared with the experimental data. The impact of cold recycling on the liquefaction yield and efficiency of the cryogenic energy storage system was investigated
The water quality of streams located in large urban agglomeration, case study of the SłuŻewiecki Stream
Authors: Wojtkowska Małgorzata , Matula Magdalena , Kozińska Paulina
Published: July 2018

The quality assessment of watercourse, located in a highly urbanized area was the goal of research. The SłuŻewiecki Stream, which flows in the southern part of the capital city of Warsaw is the subject of study. The aim of the research was to determine the tendency of the water quality changes in the SłuŻewiecki Stream, flowing in the highly urbanized area and being a sink of the non-point and industry sources of pollutions as well as the surface runoffs which comes from its catchment. The field research was conducted along the entire length of the stream in 2015 and 2016. The water samples were collected monthly from a depth to 20 cm. Water quality tests were carried out in accordance with the valid analytical methods. The obtained results point to poor water quality. Therefore it can be conducted that the development and use of the direct catchment is the one of main factors affecting the water quality in SłuŻewiecki Stream. The tributaries, often not inventoried, from built-up, populated areas, are the most polluted. Tributaries contain large amount of organic compounds and nutrients.
Effects of pyrolysis parameters on the yield and properties of biochar from pelletized sunflower husk
Authors: Wystalska Katarzyna , Malińska Krystyna , Włodarczyk Renata , Chajczyk Olga
Published: July 2018

Pyrolysis of biomass residues from agriculture and food processing industry allows production of biochars with diverse physical and chemical properties for a wide range of applications in agriculture and environmental protection. Biochars produced from pelletized sunflower husks through slow pyrolysis in the range of temperatures (480–580°C) showed total carbon of 70.53%–81.96%, total nitrogen of 1.2%, alkaline pH (9.37–10.32), low surface area (0.93–2.91 m2 g-1) and porosity of 13.23–15.43%. Higher pyrolysis temperatures resulted in lower biochar yields. With the increase in temperature the content of organic matter, nitrogen, Ca and Mg decreased whereas the increase in temperature resulted in higher contents of total carbon and phosphorus. Produced biochars showed potential for agricultural applications.
Multivariate Splines-Based Asymmetric Aerodynamic Modeling of Morphing Aircraft
Authors: Xu Xiaowu , Zhang Wei , Zhan Hao
Published: July 2018

The aerodynamic parameters of morphing aircraft can vary significantly in the morphing process; the aerodynamic data model is complex and high-order nonlinear. This paper presents a new method of aerodynamic modeling of morphing aircraft by using multivariate splines. Firstly, the aerodynamic coefficient model of morphing aircraft based on the multivariate splines model structure is presented. This model can describe symmetric and asymmetric aerodynamic forces. Then, the multivariate simple splines estimation process is introduced in detail and the concrete formulation is deduced. Finally, the final model structure is determined by error analysis, and the aerodynamic parameter polynomial model in the global coordinate system is obtained by coordinate transformation. The results show that this method can accurately describe the aerodynamic model of morphing aircraft during arbitrary symmetric and asymmetric morphing process without predicting the specific model structure of the aerodynamic parameters related to varying process.
Flutter Boundary Prediction of a Two Dimensional Airfoil in Transonic Flight Regime with the Preset Angles of Attack
Authors: Gao Guozhu , Bai Junqiang , Li Guojun , Liu Nan , Li Yufei
Published: July 2018

Angle of attack has impact on transonic flow filed and aerodynamic force, but most of current researches on flutter use zero angle hypothesis, which has no consideration about angle of attack. Therefore, we use unsteady Reynold Averaged Navier-Stokes (RANS) equation and structural dynamic equation to establish the time domain aeroelastic analysis method. The solution in time domain is the fourth-order implicit Adams linear multi-step method which is based on prediction-correction method. The numerical simulations were used to analyze the transonic flutter boundary of Isogai Case A Model which was based on zero angle condition and nonzero angle respectively. The simulation results show that the reduced flutter speed decreases as the preset angle of attack decreases between 0.73 and 0.76, which shows a 12.5% decrease of the flutter speed at the farthest. Nonzero angle makes the transonic dip weaker and wider than fully turbulent flow. Changing in angle of attack of 6°, the flutter speed in the deepest position of transonic dip has increased by 124% compared to the flutter speed of 0°. Therefore, when flutter characters of airfoil is analyzed, the effects of the initial angle of attack must be taken into account in order to analyze flutter boundary correctly. In other words, increasing the angle of attack offers a way to control the system in terms of delaying flutter.
Decision Modeling of UAV On-Line Path Planning Based on IMM
Authors: Yang Qiming , Xu Jiancheng , Tian Haibao , Wu Yong
Published: July 2018

In order to enhance the capability of tracking targets autonomously of UAV, a model for UAV on-line path planning is established based on the theoretical framework of partially observable markov decision process(POMDP). The elements of the POMDP model are analyzed and described. According to the diversity of the target motion in real world, the law of state transition in POMDP model is described by the method of Interactive Multiple Model(IMM) To adapt to the target maneuvering changes. The action strategy of the UAV is calculated through nominal belief-state optimization(NBO) algorithm which is designed to search optimal action policy to minimize the cumulative cost of action. The generated action strategy controls the UAV flight. The simulation results show that the established POMDP model can achieve autonomous planning for UAV route, and it can control the UAV to effectively track target. The planning path is more reasonable and efficient than the result of using single state transition law.
Calcifications in Thyroid Tumors on Ultrasonography: Calcification Types and Relationship with Histopathological Type
Authors: Kobayashi Kaoru , Fujimoto Tomoko , Ota Hisashi , Hirokawa Mitsuyoshi , Yabuta Tomonori , Masuoka Hiroo , Fukushima Mitsuhiro , Higashiyama Takuya , Kihara Minoru , Ito Yasuhiro , Miya Akihiro , Miyauchi Akira
Published: July 2018

The purpose of the study is to clarify the prevalence of calcifications within thyroid tumors on ultrasonography as well as the relationship between the calcification and histopathological types.

Calcifications were classified into 6 (or 8) types according to their shape, size, and region. The prevalence of calcifications and types were investigated in new outpatients and patients who underwent thyroid surgery.

Among 2,902 nodules in 2,678 new outpatients, 747 nodules (26%) had calcifications. The types showed a wide distribution. Among 941 patients with papillary carcinoma (PC), 725 patients (77%) had calcifications, and the types showed a wide distribution. 18 patients with the diffuse sclerosing variant of PC only showed punctate microcalcifications in the parenchyma (100%), 32 patients with the cyst-forming type of PC mostly fragmentary and massive types (100%), and 161 metastatic lymph nodes from PC mostly punctate microcalcifications and fragmentary types (48%). Among 337 patients with follicular carcinoma, 79 patients (23%) had calcifications, and the types were mostly fragmentary, massive, and egg-shell types. Among 41 patients with undifferentiated carcinoma, 33 patients (80%) presented with calcifications, which were mostly the massive and egg-shell types. Among 137 patients with medullary carcinoma, 99 patients (72%) had calcification, and the types showed a wide distribution. None of 173 patients with primary thyroid lymphoma had calcifications (0%).

Calcifications on ultrasonography can be one of the characteristic findings and a full understanding of the prevalence of calcifications and types will markedly contribute to the ultrasonic diagnosis of thyroid tumors.
Ti(III)-Mediated Radical-Induced Approach to a Bicyclic δ-Lactone with a Bridgehead β-Hydroxy Group
Authors: Chakraborty Tushar , Das Dipendu , Khan Hina
Published: July 2018

Herein, we portray a synthetic route to a bicyclic lactone containing a bridgehead hydroxy group, a structure that is present in many natural products of biological and medicinal relevance. Ethyl (E)-3-(dimethylphenylsilyl)-7,8-epoxyoct-2-enoate underwent radical-mediated­ reductive epoxide opening with concomitant intramolecular cyclization using Cp2Ti(III)Cl to give cis-6-(dimethylphenylsilyl)-3-oxabicyclo[4.3.0]nonan-4-one, a bicyclic lactone with a bridgehead silyl group serving as a masked hydroxy group. Furthermore, the bridgehead C–Si bond underwent stereoretentive oxidative cleavage to give cis-6-hydroxy-3-oxabicyclo[4.3.0]nonan-4-one in high yield under Tamao–Fleming oxidation conditions; this demonstrates the potential utility of this strategy in the synthesis of many natural products bearing similar hydroxylated bridgehead chiral center embedded in a bicyclic lactone framework.
Divergent Syntheses of Carbazole Alkaloids
Authors: Song Chuanjun , Chang Junbiao , Ji Feixiang , Huang He , Li Mengyang , Guo Yanqin
Published: July 2018

Starting from common intermediate methyl 1-hydroxy-9H-carbazole-3-carboxylate, synthetic routes toward murrayaquinone A, olivacine, and N-methylcalothrixin B were developed.
Perception of the Quality of Life of Tobacco Growers Exposed to Pesticides: Emphasis on Health, Hearing, and Working Conditions
Authors: Cazé Ana , Lacerda Adriana , Lüders Débora , Conto Juliana , Marques Jair , Leroux Tony
Published: July 2018

Introduction Tobacco farming exposes workers to various health risks due to the high application of pesticides needed to control pests, weeds and fungal diseases that prevent the tobacco plant growth.

Objective To analyze the perception of the quality of life of tobacco growers exposed to pesticides, with emphasis on general health, hearing, and working conditions.

Method This is a descriptive, cross-sectional study using a quantitative approach with farmers from southern Brazil. Data were collected from November of 2012 to November of 2014. For data collection, we opted for the 36-item short form health survey (SF-36) questionnaire, and a questionnaire with closed questions about health, hearing and working conditions. We evaluated a total of 78 subjects; the study group, made up of 40 tobacco farmers exposed to pesticides, and a control group of 38 participants without occupational exposure to pesticides. Both groups are residents of the same municipality, and users of the federal public health system.

Results The results showed that tobacco growers had lower quality of life scores compared with the control group. Significant differences were observed in the areas of pain and general health. There were correlations between physical elements and chronic diseases; hearing complaints and a lack of personal protective equipment use, occupation and hearing complaints, as well as general health and hearing complaints.

Conclusion Tobacco farming is a risky activity for general and hearing health, and it can impact the quality of life of those working in this field.
Failure of Immunosuppression in a Severe Haemophilia B Patient with Specific Antibody
Authors: Allain Jean-Pierre , Frommel Dominique
Published: July 2018

Prevention of a secondary response to factor IX by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor IX had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor IX antibody was not depressed. The difficulties of modifying the anamnestic response to factor IX by chemical immunosuppression may be as real as has been reported for factor VIII in classical haemophilia.
Prothrombin Determination by Means of a Chromogenic Peptide Substrate
Authors: Axelsson G , Korsan-Bengtsen K , Waldenström J
Published: July 2018

A two stage method to determine prothrombin with the chromogenic peptide substrate benzoyl-phe-val-arg-p-nitroanilide has been worked out. Citrated plasma (10 μl) was diluted in 600 μl tris buffer, pH 8.2, ionic strength 0.18 and activated with 250 μl of a commercial rabbit brain-lung thromboplastin. After 325 s incubation at 37° C 200 μl of a 1 mM solution of the chromogenic substrate was added and the increase in absorbance was recorded in a LKB-Beckman 8600 enzyme analyzer. A reading time of 1 minute (including a delay of 20 s) was used which permitted 55 analyses per hour to be carried out. An approximate linear relationship was found between ΔA/min and dilutions of normal plasma in prothrombin deficient plasma. The method is insensitive to variations of factors V, VII and X. Less than 10 % of normal plasma was needed to “normalize” plasmas deficient in factor V or VII or X.

A group of 99 dicoumarol treated patients and 23 normal subjects has been investigated using the present method and compared with a factor II-VII-X determination method. A correlation coefficient of 0.95 was found.
Inhibitory Effect of Acetylsalicylic Acid on Human Platelet Function in Normal Volunteers and in Women Using a Combined Oral Contraceptive Regime
Authors: Baele G , Thiery M , Vermeulen A , Barbier F
Published: July 2018

Six parameters related to the release reaction were measured simultaneously in 10 human volunteers prior to the intake of one single dose of 1 g acetylsalicylic acid and 1, 4, 5, 6 and 7 days later: ΔE5 with diluted collagen, ΔE10 with Thrombofax® and the serotonin-14C release by undiluted and diluted collagen, by Thrombofax and by bovine plasma. The duration of the inhibitory effect varied according to the test used. It was the most prolonged (through the 7th day) if serotonin-14C release by diluted collagen was measured.

A systematic investigation of the platelet release reaction in women taking a combined oral contraceptive was also performed. There were no statistically significant differences from a control group. No difference in acetylsalicylic acid sensitivity, measured 24 hours after intake of 1 g of aspirin, could be demonstrated.
Effect of Aspirin on Platelet Phospholipids
Authors: Valles J , Aznar J , Santos M. T
Published: July 2018

It was observed that the acetylsalicylic acid “in vitro” (final concentration 10−4 M) as well as “in vivo” (1 g of aspirin) caused a platelet phospholipids variation which basically consisted of:

1. A diminution of the phospholipids/proteins rate of 22%.

2. A reduction of sphingomyelin “in vivo” of 27.66% and “in vitro” of 16.82%.

3. An increase in phosphatidyl choline “in vivo” of 12.24% and “in vitro” 10.28%.

The possible effects that these changes might have on the platelet function are evaluated.
Rapeseed Oil and Sunflower Oil Diets Enhance Platelet In Vitro Aggregation and Thromboxane Production in Healthy Men when Compared with Milk Fat or Habitual Diets
Authors: Mutanen Marja , Freese Riitta , Valsta Liisa M , Ahola Irma , Ahlström Antti
Published: July 2018

In this highly controlled trial, 26 normolipidemic men (average age 28 years, range 18 to 60) were fed a baseline diet high in milk fat (MF) (fat 36% of energy, saturates 19%, monounsaturates 11%, polyunsaturates 4%), followed by a diet high in sunflower oil (SO) (fat 38% of energy, saturates 13%, monounsaturates 10%, polyunsaturates 13%) and another diet high in low erucic-acid rapeseed oil (RO) (fat 38% of energy, saturates 12%, monounsaturates 16%, polyunsaturates 8%). All diets were mixed natural diets with the same cholesterol contents. The baseline milk fat diet was given for 14 days and the oil diets for 24 days in a blind cross-over design. The platelet in vitro aggregation (slope %/min) induced by 1, 2 and 3 pM ADP and collagen (25 pg/ml PRP) was highly significantly (p <0.001) increased after both oil diets when compared with the results from the milk fat diet. The aggregation pattern determined by threshold collagen concentration confirmed increased collagen sensitivity of the platelets after the rapeseed oil diet (p <0.001). The enhancement of platelet aggregation was associated with increased in vitro platelet thromboxane production after the oil diets vs. the milk fat diet (p <0.05 after the sunflower oil diet and p <0.001 after the rapeseed oil diet).
Report of Scientific and Standardization Subcommittee on Neonatal Hemostasis Diagnosis and Treatment of Neonatal Thrombosis
Authors: Schmidt Barbara , Andrew Maureen
Published: July 2018

Thrombotic disease in newborn infants is common and serious enough to require effective and safe intervention (1). Flowever, neonatal thrombosis is also sufficiently rare to prompt anecdotal observations rather than controlled clinical trials. While there is an abundance of case reports in the pediatric literature, there is a conspicuous paucity of well-designed studies to guide clinical decision-making (2).

The Subcommittee on Neonatal Hemostasis of the Scientific and Standardization Committee recognizes the need for multicenter controlled clinical trials to determine the risks and benefits of different treatment modalities for neonatal thrombosis. Until such data becomes available, the following recommendations may assist clinicians in the management of newborn infants with thrombotic disease. These recommendations were endorsed by the Subcommittee after careful review of the literature and several consensus meetings.
Bacterial Expression of Biologically Active High Molecular Weight Kininogen Light Chain
Authors: Kunapuli Satya P , DeLa Cadena Raul A , Colman Robert W
Published: July 2018

Human high molecular weight kininogen (HK), a single chain plasma glycoprotein, serves as a cofactor in the contact system of blood coagulation. After cleavage by human plasma kallikrein, the nonapeptide bradykinin is released. The HK light chain (LC) contains coagulant activity, which requires both the ability to bind the contact system zymogens, prekallikrein and factor XI, and the ability to interact with negatively charged surfaces. Since bacterial expression might not be successful if carbohydrate was required for activity, we evaluated that possibility by incubating plasma HK with endoglycosydase F. Although the procedure removed detectable N-linked carbohydrate, no change in specific activity occurred. We then developed a bacterial expression system to produce recombinant HK LC. The cDNA coding for the HK LC was prepared by polymerase chain reaction (PCR), digested with restriction enzymes EcoRI and PstI, and introduced into the bacterial expression vector pKK223-3. E. coli harboring this recombinant plasmid (pSKl) expressed HK LC upon induction with isopropylthio-galactoside (IPTG). The recombinant protein (27 kDa), when transferred onto a PVDF membrane, was recognized by monospecific polyclonal anti-HK LC-antibodies. The recombinant HK LC was purified by heparin agarose affinity chromatography to homogeneity and found to have a specific activity of 28 coagulant units per mg protein, similar to the specific activity of the LC derived by proteolytic digestion of human plasma HK. We conclude: 1) The HK LC synthesized in bacteria is biologically active, and 2) the 40% carbohydrate content of the HK LC is not required for its cofactor activity.
The Effect of Suramin on Laboratory Tests of Coagulation
Authors: Horne McDonald K , Wilson Olga J , Cooper Michael , Gralnick Harvey R , Myers Charles E
Published: July 2018

The antitrypanosomal drug suramin, which has recently been under investigation as a cancer chemotherapeutic agent, has previously been found to induce heparin-like anticoagulants in treated patients. In the currently reported work suramin is shown to have an additional anticoagulant activity that is due to direct effects of the drug on procoagulant proteins. The studies were conducted with pooled normal plasma treated in vitro with suramin and with plasma samples obtained from patients who had received the drug intravenously for 2 weeks. It is demonstrated that in plasma suramin inhibits factors V, VIII, IX, X, XI, and XII, while thrombin, prothrombin, and factor VII are unaffected. The inhibition of factor V is virtually irreversible, although the effect of suramin on the other factors is readily reversed by dilution.
Pharmacodynamic Properties of Long Lasting Butyryl Heparin Derivatives in the Rabbit
Authors: Saivin S , Caranobe C , Petitou M , Lormeau J C , Houin G , Boneu B
Published: July 2018

This paper reports on the pharmacodynamic properties of butyryl derivatives of unfractionated heparin (C4-UH) and of low molecular weight heparin (C4-CY 216) after bolus intravenous injection, constant infusion and subcutaneous administration to rabbits. The pharmacodynamic properties of the two butyryl derivatives were compared to those of the parent compounds, unfractionated heparin (UH) and low molecular weight heparin (CY 216). After bolus intravenous injection of increasing doses, the disposition of the butyryl derivatives were comparable to that of their parent compounds up to 3 mg kg-1. Over this dose, their clearances became 2 to 3 times lower. These long lasting properties were confirmed by constant intravenous infusion experiments. After subcutaneous administration, the bioavailability of C4-UH remained low (10%) at any dose while that of C4-CY 216 ranged from 42 to 120%. If these findings are confirmed in man, these new derivatives open the possibility of treating established deep vein thrombosis with only one daily injection of a butyryl derivative of low molecular weight heparin.
The Reversible Antithrombin Activity of Incubated Plasma
Authors: Gomperts E. D , Stavridis J. C , Mibashan R. S
Published: July 2018

The thrombin time of normal citrated plasma is progressively prolonged on incubation in open glass tubes at 37° C. The phenomenon is dependent on the temperature and duration of incubation, on the pH, and on the concentration of calcium ions present. Platelet-rich citrated plasma fails to exhibit augmented antithrombin activity when similarly incubated, and the addition of washed platelets to platelet-poor plasma inhibits this activity. The clot retarding action of incubated plasma against thrombin is also manifested against Arvin (Ancrod), but not against Reptilase-R. This thrombin time lenghening may be inhibited by incubation with anti-antithrombin III antiserum thus indicating that the phenomenon of thrombin time lengthening is consistent with enhanced activity of antithrombin III. It is unlikely that alterations in the activity of α2-macroglobulin, is important in the reduced thrombin-coagulability of incubated plasma. Interference with the polymerisation of fibrin monomers by the physicochemical changes may contribute to the observed phenomenon.
Enhancement of Platelet Sensitivity to ADP-Aggregation by Isometric Exercise in Arteriosclerotic Patients and its Prevention
Authors: Sano Tadahiro , Motomiya Takeshi , Yamazaki Hiroh , Shimamoto Takio
Published: July 2018

A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points:

1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment.

2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positive significant correlations between the values obtained by these three methods.

3. It was proved to be highly reproducible and is thought to be useful clinically.

By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement of platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.
Factor VIII Inhibitor Associated with Chlorpromazine-Induced Hepatic Injury
Authors: Glazier Richard L , Crowell Edward B
Published: July 2018

A 90-year-old man was given chlorpromazine for sedation and 2 weeks later developed cholestatic jaundice and subsequently a factor VIII inhibitor. His death 4 weeks after institution of chlorpromazine, from massive bleeding, coupled with the autopsy finding of intrahepatic cholestatic jaundice, suggests that both adverse reactions were due to the drug.
Fibrinolytic, Factor VIII and Pulse Rate Responses to Repeated Adrenaline Infusion Followed by Haemorrhage
Authors: Britton B. J , Giddings J. C , Brooks Lynne , Bloom A. L
Published: July 2018

The role of catecholamines in the activation of coagulation and fibrinolysis following surgery remains controversial. In this study 5 dogs were infused with 1, 2, 3, 6, 9 and 12 μg kg–1 min–1 of adrenaline at twice weekly intervals and were then reexposed to 3 μg kg–1 min–1. Pulse rate and factor VIII increased after infusion of 1,2 and 3 μg kg–1 min–1 but thereafter there was a diminished response and no response on reexposure to 3 μg kg–1 min–1 although this was not significant in the case of pulse rate. Euglobulin lysis time shortened after each infusion of adrenaline and showed no development of tolerance. A control series of dogs infused with saline showed no similar changes.

Both groups of animals were then bled to a blood pressure of 60 mm Hg for 60 minutes. Pulse rate and factor VIII did not change but euglobulin lysis time shortened in both groups. The results suggest that the activation pathways for changes in factor VIII and euglobulin lysis time induced by adrenaline are separate.
Pharmacokinetics of Full Length and Two-Domain Tissue Factor Pathway Inhibitor in Combination with Heparin in Rabbits
Authors: Bregengaard Claus , Nordfang Ole , Østergaard Per , Petersen Jens G L , Meyn Giorgio , Diness Viggo , Svendsen Ove , Hedner Ulla
Published: July 2018

Tissue factor pathway inhibitor (TFPI) is a feed back inhibitor of the initial activation of the extrinsic pathway of coagulation. In humans, injection of heparin results in a 2-6 fold increase in plasma TFPI and recent studies suggest that TFPI may be important for the anticoagulant activity of heparin. Full length (FL) TFPI, but not recombinant two-domain (2D) TFPI, has a poly cationic C-terminus showing very strong heparin binding. Therefore, we have investigated if heparin affects the pharmacokinetics of TFPI with and without this C-terminus.

FL-TFPI (608 U/kg) and 2D-TFPI (337 U/kg) were injected intravenously in rabbits with and without simultaneous intravenous injections of low molecular weight heparin (450 anti-XaU/kg).

Heparin decreased the volume of distribution and the clearance of FL-TFPI by a factor 10-15, whereas the pharmacokinetics of 2D-TFPI were unaffected by heparin. When heparin was administered 2 h following TFPI the recovery of FL-TFPI was similar to that found in the group receiving the two compounds simultaneously, suggesting that the releasable pool of FL-TFPI is removed very slowly in the absence of circulating heparin.
Platelet Aggregation on Extracellular Matrix: Effect of a Recombinant GPIb-Binding Fragment of von Willebrand Factor
Authors: Dardik R , Ruggeri Z M , Savion N , Gitel S , Martinowitz U , Chu V , Varon D
Published: July 2018

Platelets in whole blood incubated on extracellular matrix (ECM) produced by bovine corneal endothelial cells under oscillatory flow conditions demonstrate extensive aggregate formation. Since both platelet-subendothelium and platelet-platelet interactions are mediated by von Willebrand factor (vWF), we used this system to examine the effect of a recombinant GPIb-binding fragment of vWF (designated RG12986), comprising residues 445-733 of the native vWF subunit, on platelet reactivity with ECM. The seven cysteines present in the RG12986 fragment were reduced and alkylated in order to achieve a monomeric conformation. The recombinant vWF fragment binds to unstimulated platelets in the absence of exogenous modulators. When added to platelet-rich plasma, it inhibits ristocetin-induced platelet agglutination. Binding of 51Cr-labeled platelets in reconstituted whole blood to ECM was inhibited by RG12986 in a dose dependent and saturable manner, with IC50 of 4 μM and maximal inhibition (about 70%) at 6 μM. Scanning electron microscope (SEM) analysis showed that addition of RG12986 to whole blood significantly inhibited platelet aggregation on ECM. The extent of inhibition observed with RG12986 at a final concentration of 4 μM was similar to that obtained with the cell adhesion peptide RGDS at the concentration of 0.1 mM. The ability of the RG12986 fragment to inhibit platelet aggregation on ECM is in agreement with the concept that blockade of vWF-GPIb interaction may inhibit further events leading to activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex and subsequent thrombus formation.
Some Relations Between Light Transmission Changes and Biochemical Parameters of Stored Platelet Packs
Authors: Järemo Petter , Edlund Bror , Berseus Olle , Kutti Jack
Published: July 2018

In the present work a computerised method for continuous monitoring of light transmission through platelet packs was evaluated. One series (Series 1) of 50 platelet concentrates was studied over a 5-day period, and thereafter the pH, extracellular lactate dehydrogenase (LDH) and platelet factor 4 (PF4) in the concentrates were determined. A second series (Series 2) of 52 concentrates was also monitored over 5 days, and thereafter the pH, extracellular LDH and intracellular concentrations of ATP, ADP and AMP were determined. 11 and 14 of the concentrates of Series 1 and 2, respectively, demonstrated long lasting transmission increases (≥ 3.0 days). In the total of 102 platelet concentrates 34 were observed to have late (<1.0 day) or no transmission increase. It is concluded, that the present optical method identifies both a group of platelet concentrates having long lasting transmission increases and a group consisting of platelet concentrates having late or no transmission increase. Compared to the latter concentrates preparations with long lasting transmission changes demonstrated significant biochemical alterations. These observations could be applicable in the quality control of platelet concentrates.
Prothrombin Activation Fragment 1 + 2 and Thrombin Antithrombin III Complexes in Patients with Angina Pectoris: Relation to the Presence and Severity of Coronary Atherosclerosis
Authors: Kienast J , Thompson S G , Raskino C , Pelzer H , Fechtrup C , Ostermann H , Loo J van de
Published: July 2018

Plasma levels of the prothrombin activation fragment 1 + 2 (F 1 + 2) and of thrombin antithrombin III complexes (TAT) were determined in 225 patients with angina pectoris undergoing coronary angiography. Oral anticoagulant therapy was associated with a marked reduction in mean Fl + 2 (0.63 vs 1.62 nmol/l, p <0.0001) and TAT levels (1.65 vs 2.23 μg/1, p <0.0001). Omitting patients on oral anticoagulants, TAT values showed a positive association with patients’ age (r = 0.18; p = 0.01) and were slightly higher in patients with a history of myocardial infarction than in those without (2.47 vs 2.11 <g/l; p = 0.06). Both Fl + 2 and TAT levels were increased in patients with angiographically verified coronary atherosclerosis as compared to patients with angina and angiographically normal coronaries (Fl + 2: 1.76 vs 1.36 nmol/1, TAT: 2.35 vs 2.00 μg/1; p-values after adjusting for age, sex and past history of myocardial infarction 0.06 and 0.11 respectively). However, no graded relationship between Fl + 2 or TAT values and severity of atherosclerosis was observed. This study provides suggestive evidence that a procoagulant state exists in patients with angina pectoris and coronary atherosclerosis. Its relevance in predicting coronary ischaemic events needs to be studied prospectively.
Enhanced Prothrombin and lntrinsic Factor X Activation on Blood Platelets from Diabetic Patients
Authors: Lupu Cristina , Calb Maria , Lonescu Mihaela , Lupu Florea
Published: July 2018

The present work was conducted to bring information about the enhanced procoagulant activity of blood platelets in diabetes mellitus, as compared to normal control platelets. The inquiry was performed on platelets from either human patients or hamsters with streptozotocin-induced diabetes. The experiments comprised functional assays of factor Xa and thrombin generation in the presence of normal or diabetic platelets, using saturating amounts of coagulation factors. The prothrombinasic and tenasic complexes activation was measured by using discontinuous amidolytic tests with chromogenic substrates (S-2238 for FXa and S-2222 for thrombin). The results showed that, in contrast to the low prothrombin and factor X converting activity of normal platelets, the thrombin and FXa generation on diabetic platelets was increased by 3-7 times for either humans or hamsters. These findings may be relevant for the pathogenesis of thrombotic complications known to occur in diabetes mellitus.
Haemostatic Variables and Menopausal Status: Influence of Hormone Replacement Therapy
Authors: Scarabin Pierre-Yves , Plu-Bureau Geneviève , Bara Lucienne , Bonithon-Kopp Claire , Guize Louis , Samama Meyer M
Published: July 2018

Large cohort studies have shown that postmenopausal estrogen use was associated with a reduction in the risk of coronary heart disease, This putative beneficial effect of hormone replacement therapy (HRT) may be partly mediated through changes in clotting factors and fibrinolytic system. We have measured haemostatic variables in 293 consecutive healthy women aged 45-54 years who attended a health check-up centre in Paris (IPC). Premenopausal women taking hormonal therapy were excluded (n = 34). Most women using HRT were given 17-β estradiol in combination with progestin. Mean levels (m ± sd) of plasma fibrinogen, factor VII coagulant activity and plasminogen activator inhibitor (PAI) were significantly higher in postmenopausal women not taking HRT (n = 99) than in premenopausal women (n = 139) within the same decade (319 ± 52 mg/dl vs 304 ± 60 mg/dl, 107 ± 17% vs 96 ± 16%, 9.73 ± 5.71 U/ml vs 7.61 ± 4.36 U/ml respectively). Allowance for main cardiovascular risk factors made no substantial differences to the results, although the effect of the menopause on fibrinogen was no longer significant. HRT (n = 21) significantly reversed the menopause-related changes in factor VII (94 ± 15%), even after adjustment for confounding factors. The same trend in both fibrinogen (294 ± 46 mg/dl) and PAI (8.22 ± 5.51 U/ml) was observed. Similar results were found in women using oral or percutaneous estrogen. Our findings suggest that 17-β estradiol in combination with progestins may protect against an increased thrombotic tendency in postmenopausal women. Randomized clinical trials are urgently needed for a better understanding of HRT effect on atherothrombotic process.
A Compound Heterozygous Protein C Deficiency with a Single Nucleotide G Deletion Encoding Gly-381 and an Amino Acid Substitution of Lys for Gla-26
Authors: Ido Masaru , Ohiwa Michiaki , Hayashi Tatsuya , Nishioka Junji , Hatada Tsuyoshi , Watanabe Yasuyuki , Wada Hideo , Shirakawa Shigeru , Suzuki Koji
Published: July 2018

We report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all exons in protein C gene in this family revealed two mutations. The first abnormality, derived from the mother, was a deletion of one of four consecutive G at nucleotide number 10758 in exon IX which would result in a frame shift mutation and completely change amino acid sequence from Gly381 in the carboxyl-terminal region of protein C. The second abnormality, derived from the father, was a single nucleotide mutation from G to A in the codon (GAG to AAG) at nucleotide number 2977 in exon III, which would result in a substitution of Lys for γ-carboxyglutamic acid (Gla)26. This change would be responsible for the reduced immunological protein C levels of the patient and the father, estimated by a monoclonal antibody which recognizes the Gla-domain in a Ca2+-dependent manner (3.8% and 57%, respectively). Partially purified abnormal protein C from the father’s plasma showed a normal amidolytic activity and a change in the electrophoretic mobility. We detected the above mutations in his family members using two methods; one was a creation of new restriction enzyme sites using mutagenic primers and the other was single nucleotide primer extension. Both methods are rapid and useful for the diagnosis of prenatal protein C abnormalities.
The Routine Measurement of Platelet Size Using Sodium Citrate Alone as the Anticoagulant
Authors: Bath P M W
Published: July 2018

Mean platelet volume (MPV), a measure of platelet size, is becoming recognised as an important marker of platelet function. However, platelets swell in edetic acid (EDTA), the Standard haematology anticoagulant, in a time-dependent manner making such measurements potentially unreliable. The effect of incubation time on MPV, and platelet distribution width (PDW), as measured in EDTA, low (1:9 volume/volume with blood) or high (1:4 v/v with blood) concentration sodium citrate was studied. MPV measured in high concentration sodium citrate did not change with time in contrast to MPV measured in either low concentration sodium citrate or EDTA which both increased in an inverse exponential fashion. MPV and PDW, measured in high concentration sodium citrate, had similar within-assay and between-assay coefficients of Variation as other platelet, red cell and white cell haematology variables measured in EDTA: MPV 1.4%, 2.1%; PDW 1.4%, 1.5%; MCV 0.4%, 0.7%; PC 3.1%, 6.1%; WCC 1.5%, 7.3%; Hb 2.1%, 2.4% respectively. MPV measured in EDTA and corrected for incubation time approximated to, but was higher than, the MPV measured in high concentration sodium citrate. PDW correlated inversely with platelet count (r = <0.415, 2p <0.001). MPV may be measured in sodium citrate (at 1:4 v/v with blood) alone with a better accuracy and reproducibility than similar measurements made in EDTA. Furthermore, such measurements are not influenced by incubation time, unlike for EDTA.
Platelet Aggregation Induced by Plasma from Type IIB von Willebrand’s Disease Patients Is Associated with an Increase in Cytosolic Ca2+ Concentration
Authors: Francesconi Maria Angela , Deana Renzo , Girolami Antonio , Pontara Elena , Casonato Alessandra
Published: July 2018

The effect of type IIB von Willebrand’s factor (vWF) on platelet cytosolic Ca2+ ion concentration, measured by means of the probe fura 2, was investigated. Seven patients with type IIB von Willebrand disease (vWD) were studied. Addition of type IIB vWD plasma to platelet suspensions induced a cytosolic calcium increase accompanied by platelet aggregation. Both processes were completely abolished by addition of the calciumchelating agent EGTA, indomethacin, peptide RGDS, and monoclonal antibodies blocking the vWF binding site on GPIb-IX (LJIB1) or the cytoadhesive receptor on GPIIb-IIIa (LJCP8). The ADP-scavenger apyrase and the protein kinase C-inhibitor staurosporine partially inhibited the rate of the cytosolic calcium increase. No direct correlation between the extent of Ca2+ rise and the phenotypic expression of IIB vWD, such as the degree of spontaneous platelet aggregation or thrombocytopenia was apparent. It is suggested that aggregation and cytosolic Ca2+ increase in platelets exposed to plasma from type IIB vWD patients is mediated by a self-potentiating mechanism involving both GPIb and GPIIb-IIIa receptors as well as the thromboxane biosynthetic pathway.
Induction of Endothelial Tissue Factor by Endotoxin and Its Precursors
Authors: Moldow Charles F , Bach Ronald R , Staskus Katherine , Rick Paul D
Published: July 2018

The structural determinants of lipopolysaccharide required for the induction of tissue factor in human umbilical vein endothelial cells were studied. Intact lipid A was essential for the induction of tissue factor whereas the incomplete lipid A precursors lipid IVA and lipid X, as well as monophosphoryl lipid A and acyloxyacyl hydrolase-treated lipopolysaccharide, were unable to induce tissue factor and tissue factor specific mRNA. However, the lipid A precursor, lipid IVA, was able to inhibit LPS-mediated induction of tissue factor; structural determinants distal to lipid A were found to be required for maximal induction of tissue factor activity and tissue factor mRNA. The presence of serum in the assay was found to amplify but was not obligate for tissue factor induction by LPS.