bluuebunny/crossref_metadata_2025 huggingface dataset:
Fate of mesoangioblasts in a vaginal birth injury model: influence of the route of administration
Authors: Mori da Cunha Marina Gabriela Monteiro Carvalho , Giacomazzi Giorgia , Callewaert Geertje , Hympanova Lucie , Russo Francesca , Vande Velde Greetje , Gijsbers Rik , Albersen Maarten , Sampaolesi Maurilio , Deprest Jan
Published: July 2018

Currently cell therapy is considered as an experimental strategy to assist the healing process following simulated vaginal birth injury in rats, boosting the functional and morphologic recovery of pelvic floor muscles and nerves. However, the optimal administration route and dose still need to be determined. Mesangioblasts theoretically have the advantage that they can differentiate in skeletal and smooth muscle. We investigated the fate of mesoangioblasts transduced with luciferase and green fluorescent protein reporter genes (rMABseGFP/fLUC) using bioluminescence, immunofluorescence and RT-PCR in rats undergoing simulated birth injury. rMABseGFP/fLUC were injected locally, intravenously and intra-arterially (common iliacs and aorta). Intra-arterial delivery resulted in the highest amount of rMABseGFP/fLUC in the pelvic organs region and in a more homogeneous distribution over all relevant pelvic organs. Sham controls showed that the presence of the injury is important for recruitment of intra-arterially injected rMABseGFP/fLUC. Injection through the aorta or bilaterally in the common iliac arteries resulted in comparable numbers of rMABseGFP/fLUC in the pelvic organs, yet aortic injection was faster and gave less complications.
The crustal geophysical signature of a world-class magmatic mineral system
Authors: Heinson Graham , Didana Yohannes , Soeffky Paul , Thiel Stephan , Wise Tom
Published: July 2018

World-class magmatic mineral systems are characterised by fluid/melt originating in the deep crust and mantle. However, processes that entrain and focus fluids from a deep-source region to a kilometre-scale deposit through the crust are unclear. A magnetotelluric (MT) and reflection seismic program across the margin of the Gawler Craton, Australia yield a distinct signature for a 1590 Ma event associated with emplacement of iron-oxide copper gold uranium (IOCG-U) deposits. Two- and three-dimensional MT modelling images a 50 km wide lower-crustal region of resistivity <10 Ωm along an accreted Proterozoic belt. The least resistive (~1 Ωm) part terminates at the brittle-ductile transition at ~15 km, directly beneath a rifted sedimentary basin. Above the brittle-ductile transition, three narrow low-resistivity zones (~100 Ωm) branch to the surface. The least resistive zone is remarkably aligned with the world-class IOCG-U Olympic Dam deposit and the other two with significant known IOCG-U mineral occurrences. These zones are spatially correlated with narrow regions of low seismic reflectivity in the upper crust, and the deeper lower-crust conductor is almost seismically transparent. We argue this whole-of-crust imaging encapsulates deep mineral system and maps pathways of metalliferous fluids from crust and mantle sources to emplacement at discrete locations.
Codon usage clusters correlation: towards protein solubility prediction in heterologous expression systems in E. coli
Authors: Pellizza Leonardo , Smal Clara , Rodrigo Guido , Arán Martín
Published: July 2018

Production of soluble recombinant proteins is crucial to the development of industry and basic research. However, the aggregation due to the incorrect folding of the nascent polypeptides is still a mayor bottleneck. Understanding the factors governing protein solubility is important to grasp the underlying mechanisms and improve the design of recombinant proteins. Here we show a quantitative study of the expression and solubility of a set of proteins from Bizionia argentinensis. Through the analysis of different features known to modulate protein production, we defined two parameters based on the %MinMax algorithm to compare codon usage clusters between the host and the target genes. We demonstrate that the absolute difference between all %MinMax frequencies of the host and the target gene is significantly negatively correlated with protein expression levels. But most importantly, a strong positive correlation between solubility and the degree of conservation of codons usage clusters is observed for two independent datasets. Moreover, we evince that this correlation is higher in codon usage clusters involved in less compact protein secondary structure regions. Our results provide important tools for protein design and support the notion that codon usage may dictate translation rate and modulate co-translational folding.
The Functional Alterations in Top-Down Attention Streams of Parkinson’s disease Measured by EEG
Authors: Bin Yoo Hye , Concha Edgar Omar de la , De Ridder Dirk , Pickut Barbara A. , Vanneste Sven
Published: July 2018

Early and moderate Parkinson’s disease patients seem to have attention dysfunctions manifested differentially in separate attention streams: top-down and bottom-up. With a focus on the neurophysiological underpinnings of such differences, this study evaluated source-localized regional activity and functional connectivity of regions in the top-down and bottom-up streams as well as any discordance between the two streams. Resting state electroencephalography was used for 36 Parkinson’s disease patients and 36 healthy controls matched for age and gender. Parkinson’s disease patients showed disproportionally higher bilateral gamma activity in the bottom-up stream and higher left alpha2 connectivity in the top-down stream when compared to age-matched controls. An additional cross-frequency coupling analysis showed that Parkinson’s patients have higher alpha2-gamma coupling in the right posterior parietal cortex, which is part of the top-down stream. Higher coupling in this region was also associated with lower severity of motor symptoms in Parkinson’s disease. This study provides evidence that in Parkinson’s disease, the activity in gamma frequency band and connectivity in alpha2 frequency band is discordant between top-down and bottom-up attention streams.
3D Flower-like β-MnO2/Reduced Graphene Oxide Nanocomposites for Catalytic Ozonation of Dichloroacetic Acid
Authors: Li Gang , Li Kezheng , Liu Aijuan , Yang Ping , Du Yukou , Zhu Mingshan
Published: July 2018

Considering the potential use of manganese oxide based nanocomposite in catalytic ozonation of water contaminant, we report unique three-dimensional (3D) nanoarchitectures composed of β-MnO2 and reduced graphene oxide (RGO) for catalytic ozonation of dichloroacetic acid (DCAA) from drinking water. The catalytic results show that the 3D β-MnO2/RGO nanocomposites (FMOG) can be used as efficient and stable ozonation catalysts to eliminate DCAA from water. The probable mechanism of catalytic ozonation was also proposed by detecting intermediates using gas chromatography-mass spectrometry. This result likely paves a facile avenue and initiates new opportunities for the exploration of heterogeneous catalysts for the removal of disinfection by-products from drinking water.
Integrated Polymer Composites for Electro-responsive Drug Delivery
Authors: Pradeep P. , Kumar P. , Choonara Y. E. , Pillay V.
Published: July 2018

The notions of “on-demand” and “on–off” therapeutic intervention fits perfectly with electro-responsive drug delivery (ERDD) systems, wherein an external modulation of bioactive release can be realised and even programmed. Conventionally, electroactive candidates such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene were blended with polymeric or peptide hydrogels. However, the recent interests in ERDD derive from the integration of material composites (such as carbon nanotubes, graphene oxide, clay enclatherates, and microtubes) together with responsive hydrogels to provide enhanced and more electro-controllable drug delivery platforms. This chapter provides an insight into recent advances in integrated polymer composites for ERDD and a molecular mechanistic outlook to the performance and setup of such stimuli responsive systems.
Biologically-inspired Stimuli-responsive DDS
Authors: Kim Jeong-Hwan
Published: July 2018

The focus of this chapter is the use of bio-inspired, bioengineered or biomimetic systems that find tremendous application in tissue engineering, amongst other applications. Essentially, such systems either have a biological component integrated into the material component or materials that have been designed based on natural or synthetic smart materials. In particular, the chapter will review the use of bio-inspired hierarchical nanocomposites as stimuli-triggered drug deliverable scaffolds in 3-D/4-D-bioprinting, tissues regeneration, vascularization, and biological coatings.
Stimuli-responsive Material Inspired Drug Delivery Systems and Devices
Authors: Manchineella Shivaprasad , Govindaraju Thimmaiah
Published: July 2018

Stimuli-responsive materials, owing to the fascinating feature of the controlled release of the payload, have been actively researched to develop smart materials systems and devices for drug delivery applications. Such devices could be controlled using a variety of physical, chemical and biological stimuli such as temperature, electric field, ultrasound, magnetic field, pH, ionic strength, enzymes, endogenous chemical molecules and receptors, and thus provide control over the temporal release of the drug. This chapter summarises the various aspects of such materials inspired systems and devices, and introduces their application in the field of drug delivery and therapeutics.
Enzyme-linked immunosorbent assay for aflatoxin B1using a portable pH meter as the readout
Authors: Chen Juanjuan , Wang Lixu , Zhao Mengmeng , Huang Da , Luo Fang , Huang Liying , Qiu Bin , Guo Longhua , Lin Zhenyu , Chen Guonan
Published: July 2018

A simple and portable biosensor was developed for aflatoxin B1determination using a portable pH meter as the readout.
Tailored transition metal-doped nickel phosphide nanoparticles for the electrochemical oxygen evolution reaction (OER)
Authors: Man Ho-Wing , Tsang Chui-Shan , Li Molly Meng-Jung , Mo Jiaying , Huang Bolong , Lee Lawrence Yoon Suk , Leung Yun-chung , Wong Kwok-Yin , Tsang Shik Chi Edman
Published: July 2018

Foreign transition metals are doped into the nickel phosphide nanoparticles through a simple wet-chemical process to show a high level of doping without significant distortion of crystal structure and morphology, which endows excellent activity in the electrochemical oxygen evolution reaction.
Probing the π → π* photoisomerization mechanism of trans-azobenzene by multi-state ab initio on-the-fly trajectory dynamics simulations
Authors: Xu Chao , Yu Le , Gu Feng Long , Zhu Chaoyuan
Published: July 2018

Global nonadiabatic switching on-the-fly trajectory surface hopping simulations at the 5SA-CASSCF(6,6)/6-31G quantum level have been employed to probe the photoisomerization mechanism of trans-azobenzene upon ππ* excitation within four coupled singlet low-lying electronic states (S0, S1, S2, and S3).
Ion mobility action spectroscopy of flavin dianions reveals deprotomer-dependent photochemistry
Authors: Bull James N. , Carrascosa Eduardo , Giacomozzi Linda , Bieske Evan J. , Stockett Mark H.
Published: July 2018

Photo-induced proton transfer, deprotomer-dependent photochemistry, and intramolecular charge transfer in flavin anions are investigated using action spectroscopy.
Collision-induced dissociation of sodiated glucose, galactose, and mannose, and the identification of anomeric configurations
Authors: Huynh Hai Thi , Phan Huu Trong , Hsu Po-Jen , Chen Jien-Lian , Nguan Hock Seng , Tsai Shang-Ting , Roongcharoen Thantip , Liew Chia Yen , Ni Chi-Kung , Kuo Jer-Lai
Published: July 2018

Different dehydration barrier heights of cis and trans configurations between O1 and O2 provide a simple and fast anomeric configuration identification.
Targeting heme oxygenase-1 by quercetin ameliorates alcohol-induced acute liver injury via inhibiting NLRP3 inflammasome activation
Authors: Liu Shu , Tian Lei , Chai Guangrui , Wen Bo , Wang Bingyuan
Published: July 2018

Quercetin can ameliorate alcohol-induced acute liver injury via inducing heme oxygenase-1 and inhibiting NLRP3 inflammasome activation.
Comparative effects of trifluoromethyl- and methyl-group substitutions in proline
Authors: Kubyshkin Vladimir , Pridma Stanislav , Budisa Nediljko
Published: July 2018

What is the outcome of trifluoromethyl-/methyl-substitution in each position of the proline ring? Look inside to find out.
A 3D graphene current collector boosts ultrahigh specific capacity in a highly uniform Prussian blue@graphene composite as a freestanding cathode for sodium ion batteries
Authors: Chu Hang , Pei Yu , Cui Zheng , Steven Craig , Dong Pei , Ajayan Pulickel M. , Ye Mingxin , Shen Jianfeng
Published: July 2018

A highly uniform Prussian blue/graphene aerogel with a 3D structure was prepared, which reached an ultrahigh specific capacity as a composite electrode.
Predicted microlensing events from analysis of Gaia Data Release 2
Authors: Bramich D. M.
Published: July 2018

Context. Astrometric microlensing can be used to make precise measurements of the masses of lens stars that are independent of their assumed internal physics. Such direct mass measurements, obtained purely by observing the gravitational effects of the stars on external objects, are crucial for validating theoretical stellar models. Specifically, astrometric microlensing provides a channel to direct mass measurements of single stars for which so few measurements exist. Microlensing events that also exhibit a detectable photometric signature provide even stronger lens mass constraints.

Aims. I use the astrometric solutions and photometric measurements of ~1.7 billion stars provided by Gaia Data Release 2 (GDR2) to predict microlensing events during the nominal Gaia mission and beyond. This will enable astronomers to observe the entirety of each event, including the peak, with appropriate observing resources. The data collected will allow precise lens mass measurements for white dwarfs and low-mass main sequence stars (K and M dwarfs) helping to constrain stellar evolutionary models.

Methods. I search for source-lens pairs in GDR2 that could potentially lead to microlensing events between 25th July 2014 and 25th July 2026. I estimate the lens masses using GDR2 photometry and parallaxes, and appropriate model stellar isochrones. Combined with the source and lens parallax measurements from GDR2, this allows the Einstein ring radius to be computed for each source-lens pair. By considering the source and lens paths on the sky, I calculate the microlensing signals that are to be expected.

Results. I present a list of 76 predicted microlensing events. Nine and five astrometric events will be caused by the white dwarf stars LAWD 37 and Stein 2051 B, respectively. A further nine events will exhibit detectable photometric and astrometric signatures. Of the remaining events, ten will exhibit astrometric signals with peak amplitudes above 0.5 mas, while the rest are low-amplitude astrometric events with peak amplitudes between 0.131 and 0.5 mas. Five and two events will reach their peaks during 2018 and 2019, respectively. Five of the photometric events have the potential to evolve into high-magnification events, which may also probe for planetary companions to the lenses.
Update Schwangerschaftsrhinitis
Authors: Friebe-Hoffmann U. , Lindemann J.
Published: July 2018

Als sog. Schwangerschaftsrhinitis (SSR) wird eine mehrwöchige, schwangerschaftsbegleitende nasale Obstruktion bezeichnet, die sich durch eine Schwellung der
Mukosa sowie vermehrte Sekretion ohne Hinweis auf eine Entzündung, Infektion, Allergie oder Raumforderung auszeichnet und deren Symptome nach der Geburt rasch
wieder verschwinden. Die SSR zählt zu den endokrinen nasalen Hyperreaktivitäten. Etwa ein Viertel aller Schwangeren ist von diesem Krankheitsbild betroffen, das
zu jedem Zeitpunkt der Schwangerschaft auftreten kann. Pathophysiologisch werden vor allem hormonelle Einflüsse diskutiert, Rauchen sowie eine vorbestehende
Hausstaubmilbenallergie gelten als Risikofaktoren. Nachfolgend stellen wir ein stufentherapeutisches Konzept für die Behandlung der SSR vor und diskutieren die
aktuelle Literatur.
Liebe Leserin, lieber Leser
Authors: Bergmann Günther
Published: July 2018

Conditio Humana – so der Titel der Arbeit von Arthur Trenkel, dem Nestor und – gemeinsam mit K.Knoepfel – Mentor der Deutschen Balint Gesellschaft in den 70 er Jahren.
Trans-kulturelle Ost-West Fallbesprechungsgruppe – ein Praxisbericht (Hashizume – Schüffel Group)
Authors: Deter Hans-Christian
Published: July 2018

Es wird berichtet, dass Fallbesprechungsgruppen auf deutschen und japanischen Psychosomatik-Kongressen mit Mitgliedern aus verschiedenen Kulturkreisen entwickelt wurden. Hierbei wird ein medizinischer Fall von einem Teilnehmer, meist in Englischer Sprache präsentiert. Nach klärenden Rückfragen diskutieren die Teilnehmer aus einem Land/einer Kultur getrennt den Fall in der eigenen Sprache. Die jetzigen interessanten Erfahrungen aus den Gruppen der Chinesen, Japaner und Europäer von Ärzten und Psychologen wurden bei diesem Treffen zum Schluss zusammengetragen und noch einmal mit allen Teilnehmern in Englischer Sprache diskutiert. Diese Art von Fallbesprechungsgruppen führte zu neuen Einsichten und Erlebnissen der Teilnehmer. Die Bedeutung kultureller Bedingungen um eine Krankheit, die Arzt- Patienten Beziehung und die Art der Behandlung zu verstehen, können vertraut, aber manchmal auch ziemlich überraschend sein.
Factor VII Mie: Homozygous Asymptomatic Type I Deficiency Caused by an Amino Acid Substitution of His (CAC) for Arg(247) (CGC) in the Catalytic Domain
Authors: Ohiwa Michiaki , Hayashi Tatsuya , Wada Hideo , Minamikawa Kouzou , Shirakawa Shigeru , Suzuki Koji
Published: July 2018

We found hereditary factor VII deficiency in a clinically asymptomatic family, and characterized their factor VII gene and the abnormal molecule using recombinant DNA techniques. The propositus was a 45-year-old woman who was noted to have a prolonged prothrombin time. The level of factor VII antigen of the patient was 25.9% of that of normal individuals and the level of factor VII activity was 28% and 24%, when tested using rabbit brain tissue factor and human placental tissue factor in a one-stage clotting assay, respectively. Two of her sisters had almost the same reduced levels of factor VII antigen and activity, and her parents who are first cousins, a son, a daughter and a niece had moderately reduced leves of both factor VII activity and antigen. To identify the mutation site, all the coding exons and exon-intron boundaries of the factor VII gene of the propositus were amplified using the polymerase chain reaction (PCR), then subcloned and sequenced. One mis- sense mutation (G to A) was identified in exon VIII of the gene resulting in an amino acid substitution of His(CAC) for Arg(247)(CGC) in the gene product. PCR using a mutagenic primer to introduce a new kpaL I site into the mutant allele of the patient’s factor VII gene revealed that this allele was inherited in the affected individuals in the pedigree. Transient expression assays using BHK cells transfected with an expression vector containing the mutant factor VII cDNA suggested that this mutation leads to factor VII deficiency by impairing secretion of the mutated factor VII. This is the first report of a single point mutation which induces factor VII deficiency with both activity and antigen reduced in parallel.
Metabolism of the Coagulation Factors of the Prothrombin Complex in Hypothyroidism in Man
Authors: van Oosterom Allan T , Kerkhoven Peter , Veltkamp Jan J
Published: July 2018

The metabolic rate of prothrombin, factors VII, IX and X, was studied in nine hypothyroid patients. Disappearance rates of the four vitamin-K-dependent factors, called the prothrombin complex, were measured after assumedly complete blocking of their synthesis with adequate doses of a coumarin congener (acenocoumarol). Reappearance rates were assessed by induction of synthesis with high doses of vitamin K1 (phytomenadion) when stable hypocoagulability had been achieved. Normal values for these rates were derived from earlier studies in our laboratory. In hypothyroid patients the rates of both disappearance and reappearance were significantly slower for all factors tested. Practical consequences of these observations are discussed.

The initial level of factor-IX activity in all nine patients was substantially lower than in normal individuals. Therapy by thyroxine-substitution led to normal levels of factor-IX. This implies a divergency in the retardation of the breakdown and production rates in hypothyroidism. The reappearance rate was indeed found to be more retarded than the disappearance rate.
Factor VIII Inhibitor and Bronchogenic Carcinoma
Authors: Al-Ismail S A D , Parry D H , Moisey C U , Bloom A L
Published: July 2018

An inhibitor to procoagulant factor VIII (FVIIIC) developed in a patient three years after palliative resection of a bronchogenic carcinoma. The inhibitor was not active against ristocetin cofactor but possibly had some activity against factor XI. It responded to immunosuppressive therapy. This is apparently the first reported association of carcinoma and factor VIII inhibitor.
Thrombin-Like and Factor X-Activator Components of Bothrops Snake Venoms
Authors: Nahas Linda , Kamiguti Aura S , Barros M Alice R
Published: July 2018

A comparative study on the coagulant activity of snake venoms was carried out in 26 Bothrops species, using specific clotting systems for the thrombin-like and the factor X- activator activities. With only two exceptions (B. erythromelas and B. castelnaudi) all venoms showed thrombin-like activity, since they were able to clot fibrinogen directly. The absence of thrombin-like action of B. erythromelas venom is due to a fibrinogenolytic effect. Five venoms (B. atrox asper, B. bilineatus bilineatus, B. cotiara, B. fonsecai and B. itapetiningae) were unable to produce a prothrombin activator when preincubated with serum, factor V, and phospholipid. None of the venoms seems to require factors VII, VIII, IX, XII and XIII for their complete coagulant action. Direct prothrombin activation was observed in most of the Bothrops venoms, alone or combined with thrombin-like and factor X-activator activities.

An anticoagulant activity was exhibited by B. castelnaudi venom, probably due to an. anti- Xa action. This study points out that the coagulant activity of snake venoms varies within the same genus and must be characterized for each species. Thus, in Bothrops venoms the thrombin-like and factor X-activator components are not always associated, the coagulant effect may be related only to one of the components.
The Effect of Prophylaxis with Low Dose Heparin on Blood Coagulation Parameters
Authors: Hedlund Per Olov , Blombäck Margareta
Published: July 2018

Heparin was administered subcutaneously 5.000 IU twice daily using a double blind method to ten of twenty-one patients undergoing transvesical prostatectomy.

Platelet count, APTT, thrombin time, Reptilase time, Normotest, fibrinogen, Factor- VIII, ethanol gelation test, antithrombin III, fibrinolytic degradation products, α1-antitrypsin and α2-macroglobulin were studied pre- and postoperatively up to the 10th postoperative day. Statistical analysis of parameters of blood coagulation and fibrinolysis showed no significant difference between the two groups. The mechanism by which low dose heparin exerts its thromboprophylactic effect could not be elucidated from the study of the investigated parameters. The laboratory data gave no indication to a possible increased risk of postoperative hemorrhage.
Interactions between Human Plasma Proteins and Heparin-Poly(Methyl Methacrylate) Copolymer
Authors: Boffa M C , Labarre D , Jozefowicz M , Boffa G A
Published: July 2018

A solid Heparin-PMMA copolymer has been synthetized by a radical polymerization of methyl methacrylate from oxidative reaction initiated by Ce4+ ions in the presence of heparin. Covalently linked heparin was 10% of copolymer weight. The antithrombin activity of the copolymer corresponded to 1% of grafted heparin. PMMA sequence of the copolymer played the leading role in fibrinogen, immunoglobulins, transferrin and albumin adsorption. These proteins adsorbed on the copolymer, showed different competitive desorption pattern in the presence of whole plasma: fibrinogen presented the highest degree of affinity for the copolymer. The heparin part of the copolymer was responsible for antithrombin III adsorption and for decrease of factor V activity. Active antithrombin III was eluted. An inactivation of factor V in plasma was observed using high concentrations of soluble heparin. This result suggested that copolymer heparin chains, even devoid of antithrombin activity, were involved in this inactivation. With Heparin-PMMA copolymer, plasma clotting pro-enzymes behaved differently than on heparin-sepharose copolymer: disappearance of factor XI activity, decrease in prekallikrein activity and activation of factor IX were observed. PMMA sequences were responsible for factor IX activation.
Complement-Dependent and Complement-Independent Interactions of Bacterial Lipopolysaccharides and Mucopeptides with Rabbit and Human Platelets
Authors: Semeraro N , Colucci M , Vermylen J
Published: July 2018

The effect of 10 commercial lipopolysaccharides (LPS) and of 5 highly purified LPS with variable but defined polysaccharide content, two LPS from anaerobic bacteria, two mucopeptides and two meningococcal polysaccharides, was studied on rabbit and human platelets. All the LPS preparations induced aggregation in rabbit heparinized platelet-rich plasma (PRP) but to differing degrees. However, a preparation consisting essentially of lipid A (from Salmonella minnesota Re 595) was one of the most active. The mucopeptides were very potent whereas the meningococcal polysaccharides had no effect. The activity was abolished by inactivation of complement. The lack of ability of LPS and mucopeptides to aggregate rabbit platelets in ethyleneglycol tetraacetic acid (EGTA) – PRP suggests that the mechanism depends on activation of the classical pathway of complement. None of the bacterial products induced aggregation of human platelets.

When washed rabbit platelets are mixed with complement-depleted rabbit serum and calcium chloride, generation of thrombin occurs. Washed platelets contribute to thrombin generation by providing factor V, a factor X activating activity, and possibly phospholipid (Brit. J. Haemat. 36: 107, 1977). All the LPS preparations but not the mucopeptides or meningococcal polysaccharides enhanced the rate of thrombin formation by enhancing the factor X activating activity of rabbit or human platelets.

It is concluded that LPS affect rabbit platelets both by complement-dependent and complement-independent mechanisms, but human platelets only by the complement- independent pathway. Mucopeptides react with platelets only by the complement-dependent way and have no effect on human platelets.
Aggregation of Gel-Filtered Guinea-Pig Platelets by Lipoproteins
Authors: Fujitani Buichi , Tsuboi Toshimichi , Yoshida Kouichi , Shimizu Masanao
Published: July 2018

Very low density lipoproteins (VLDL) and low density lipoproteins (LDL) were isolated from serum of hypercholesterolemic guinea-pigs, and the effect of these lipoproteins on guinea-pig platelets was studied. VLDL (>100 μg/ml) and LDL (>100 μg/ml) were found to cause aggregation of gel-filtered platelets (GFP), although the extent of GFP aggregation by LDL was smaller than that by VLDL. In platelet-rich plasma, however, lipoproteins could not induce platelet aggregation. VLDL and LDL even at the low concentrations at which lipoproteins alone could not induce aggregation potentiated ADP-induced aggregation of GFP. VLDL-induced aggregation of GFP was inhibited by apyrase (0.2–1.0 mg/ml) in a concentration-related manner. Prostaglandin E1, dipyridamole, potassium cyanide and ethylenediaminetetraacetic acid inhibited VLDL- and ADP-induced aggregation of GFP in the almost same degree. Inhibitions of VLDL-induced GFP aggregation by acetylsalicylic acid and albumin were slightly stronger than that of ADP-induced aggregation. These findings suggest that lipoproteins modulate platelets so that endogenous ADP can be released from platelets.
The Action Mechanism of the Purified Platelet Aggregation Principle of Trimeresurus mucrosquamatus Venom
Authors: Ouyang Chaoho , Teng Che-Ming
Published: July 2018

The minimal concentration of the platelet aggregation principle (Platelet Aggregoserpen- tin, PAS) necessary to induce platelet aggregation was 10 ng/ml, about one-hundredth of that of the crude venom. PAS induced the release of platelet factors 3 and 4 from platelets, but the released platelet factor 3 was easily inactivated by the anti-phospholipid effect of PAS. Pretreatment of platelets with neuraminidase potentiated PAS-induced platelet aggregation. PAS-induced platelet aggregation was independent on released ADP; it could occur in the ADP-removing systems, such as apyrase or a combination of phosphoenolpyruvate and pyruvate kinase. However, PAS-induced platelet aggregation could be inhibited by adenine nucleotides and adenosine.

PAS-induced platelet aggregation was inhibited by some anti-inflammatory agents, antimalarial drugs, local anesthetics, antihistamine and smooth muscle relaxants. After deaggregation of PAS-treated platelets, thrombin and sodium arachidonate could further induce platelet aggregation, but ADP and second dose of PAS could not. It is concluded that PAS-induced platelet aggregation is due to prostaglandin synthesis. Recent literatures on the mechanism of platelet aggregation were surveyed and the actions of PAS were discussed.
Plasma Thrombin Assay using a Chromogenic Substrate in Disseminated Intravascular Coagulation due to Snake Bite Envenomation
Authors: Herrmann R P , Bailey P E
Published: July 2018

Using the chromogenic substrate, Tos-Gly-Pro-Arg-pNA-HCL (Chromozym TH, Boehringer Mannheim) plasma thrombin was estimated in six cases of envenomation by Australian elapid snakes. All patients manifested findings chracteristic of defibrination due to envenomation by these snakes. Fibrin-fibrinogen degradation products were grossly elevated, as was plasma thrombin in all cases.

Following treatment with antivenene, all abnormal coagulation parameters returned rapidly towards normal by 24 hours and plasma thrombin disappeared.
Detection and Partial Purification of a Natural Heparin Inhibitor from Hog Small Intestine
Authors: Gertler Menard M , Chien Mingjien , Yue Robert H
Published: July 2018

A natural occurring heparin inhibitor was detected and was partially purified from the mucosa of hog small intestine. The mucosa was homogenized and was extracted overnight in 0.15 M NaCl, 0.01 M imidazole, 0.001 M EDTA, pH 6.5. When the extract was made to 85% saturation in ammonium sulfate, a large quantity of heparin neutralizing activity was detected in the precipitate. Each small intestine contains approximately 35,000 units of heparin neutralizing activity. This heparin inhibitor was further purified by the procedures of zinc sulfate precipitation, ammonium sulfate fractionation, ethanol precipitation and heparin-sepharose chromatography. A 37 fold partial purification with 15% overall recovery was achieved to yield heparin inhibitor with specific activity of 50-65 units per mg of protein.
Interfering Factors in the Assay of Plasminogen Activators by the Fibrin Plate Method
Authors: Wijngaards G
Published: July 2018

The assay of plasminogen activator activities on fibrin plates was re-evaluated with special reference to fibrinolysis inhibitors present in samples and in fibrin plates. The nature, action and stability of inhibiting material were studied in tissues with considerable differences in activator and inhibitor contents! human lung, liver and placenta. Extracts were tested for inhibitory capacity against purified human uterine tissue plasminogen activator, urokinase and plasmin on fibrin plates prepared from different grades of fibrinogens and fibrin.

The tissue extracts inhibited fibrinolysis on fibrin plates to varying degrees, dependent on the sample medium, the type of fibrin plate and the kind of plasminogen activator. The influence of inhibitors in the sample and in the fibrin plate was partly abolished by the presence of 2 M KSCN in the sample. The procedure for preparing the samples as described by Astrup and Albrechtsen did not completely eliminate the inhibitory action against the added plasminogen activators.

Comparison of urokinase inhibition with tissue activator inhibition by the tissue extracts as to the degree of denaturation in the Astrup and Albrechtsen procedure showed that they have much in common. Nevertheless, some differences were found which indicated the possible existence of separate urokinase and tissue activator inhibitors or of different inhibition mechanisms for these plasminogen activators.
Somatostatin-Induced Changes in the Hemostasis of Rats
Authors: Long Michael W , Micossi Piero , Pontiroli Antonio E , Dunbar Joseph C , Foà Piero P , Henry Raymond L
Published: July 2018

Somatostatin (SRIF) given intravenously, either as a single bolus or as a 2 hr infusion caused a significant prolongation of partial thromboplastin time (PTT) and depressed platelet counts and platelet aggregation in the rat. Following daily injections of protamine- zinc SRIF for 2 weeks the platelet count returned to normal, PTT remained prolonged and platelet aggregation was enhanced. The doses of SRIF used in this work were adequate to suppress the secretion of insulin and glucagon by the isolated pancreatic islets of treated animals.
The Shape of the Fibrinogen Molecule: Sausage or Banana?
Authors: Lederer K
Published: July 2018

The experimental results and the interpretation of small angle X-ray scattering measurements by the author and Hammel (1975) and of small angle neutron scattering measurements by Marguerie and Stuhrmann (1976) on dilute solutions of bovine fibrinogen are compared. The potential of both methods to discern straight and bent cylindrical structures is demonstrated. The study arrives at the conclusion that the question whether the fibrinogen molecule resembles more a banana or a straight sausage cannot be safely decided by the available data. This justifies the previous suggestion of the author to imagine the fibrinogen molecule as a swollen sausage 450 Å long and 90 Å thick with conceivable flexibility, a molecular model of sufficient universality to include the banana-shaped model of Marguerie and Stuhrmann (1976) as a special case.
Immunohistochemical and Histochemical Investigations on In Vivo Thrombolysis with Urokinase in Rabbits
Authors: Hisano Shuusuke , Sueishi Katsuo , Ishii Yutaka , Tanaka Kenzo
Published: July 2018

Using human urokinase in vivo thrombolysis was studied in autologous artificial thrombi in the pulmonary circulation of rabbits by immunofluorescence and Todd’s fibrinolysis autography techniques.

As compared to the control thrombi of the untreated rabbits, a small increase of thrombolysis was found in the rabbits treated with urokinase.

Urokinase fluorescence was observed in the leukocytes, but not along the fibrin fibrils in the thrombi of the rabbits treated with urokinase. By Todd’s fibrinolysis autography, lytic areas were observed around aggregated leukocytes in the thrombi of the rabbits treated with urokinase.

The small lysis of autologous artificial thrombi of rabbits by human urokinase may be caused by (1) low affinity of human urokinase for rabbit plasminogen, (2) weak adsorption of human urokinase to rabbit fibrin, (3) phagocytosis of human urokinase by leukocytes and (4) high level of antifibrinolytic activity of rabbit plasma.
Diagnostic Efficacy of Plasma Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-2 in Differentiation of Hepatocellular Carcinoma from Cirrhosis
Authors: Song Kyung Soon , Lee Anna , Choi Jong Rak , Kwon Oh Hun
Published: July 2018

We determined the plasma antigen levels of urokinase-type plasminogen activator(u-PA) and plasminogen activator inhibitor 2(PAI-2) in 41 patients with hepatocellular carcinoma and 28 patients with different stages of liver cirrhosis. No significant differences of u-PA and PAI-2 levels were calculated between the two groups of tumor patients (HCC) and liver cirrhosis without tumor (non-HCC).Within both study groups, no significant differences were found in u-PA and PAI-2 levels of the different Child categories. Discriminative functions of both u-PA and PAI-2 (total error count estimates of 43.1% and 43.6%, respectively), were low compared to that (29.0%) of alpha-fetoprotein (AFP). The combinations of AFP and u-PA lowered the total error rate (21.9%) more than that of each marker alone. However, whether plasma u-PA and PAI-2 may be considered as a risk factor further investigation was needed and our findings raise the question as to whether these markers could be considered as useful screening markers for earlier detection of HCC in liver cirrhosis because discriminant functions of u-PA and PAI-2 were not significant.

Sensitivities and specificities of u-PA and PAI-2 were also not high enough, resulting in the ranges of total diagnostic efficiency from 43% to 50%, and, from 49% to 63% , respectively, at different cut-off values. No direct relationship was detected between AFP and u-PA, between AFP and PAI-2, and between u-PA and PAI-2.
“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate
Authors: Arrighi Silvana , Rossi Roberta , Borri Maria Giuseppina , Lesnikov Vladimir , Lesnikov Marina , Franco Elena , Divizia Maurizio , Santis Maria Elena De , Bucci Enzo
Published: July 2018

To improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.

The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.
Residence Time in Niches of Stagnant Flow Determines Fibrin Clot Formation in an Arterial Branching Model - Detailed Flow Analysis and Experimental Results
Authors: Reininger Armin J , Reininger Cornelia B , Heinzmann Ulrich , Wurzinger Laurenz J
Published: July 2018

Deposition of blood components in branching flow has been investigated primarily with regard to platelets. We instead examined thrombin-induced fibrin clot formation in separated laminar as well as turbulent branching flow. The most rapid clot growth and largest clot mass was obtained at the lowest inflow rate. Increased inflow reduced the clot size and turbulence completely prevented clot formation. Examination of corresponding flow conditions revealed the recirculation zone in laminar flow to be characterized by two stationary, counterrotating vortices. Niches of stagnant flow, exhibiting long residence times, low wall shear rates and characterized by convergent flow, were spared between the bulk flow and these vortices. Here, fibrin clot growth continued even when shear rates were increased more than 100-fold. Our results indicate that, in branching flow, the long residence times and convergent flow characteristic of flow niches rather than shear rate are critical for fibrin clot formation.
Changes in Haemostatic Variables Induced by Oral Contraceptives Containing 50 μg or 30 μg Oestrogen: Absence of Dose-dependent Effect on PAI-1 Activity
Authors: Scarabin Pierre-Yves , Plu-Bureau Geneviéve , Zitoun Daniéle , Bara Lucienne , Guize Louis , Samama Michel Meyer
Published: July 2018

Several studies have suggested a dose-response relation between the oestrogen content of oral contraceptive (OC) and the risk of both venous thrombosis and arterial disease, when oestrogen doses were higher than 50 μg. However, there is no clear epidemiological evidence for a decrease in thrombotic risk with formulations containing less than 50μg oestrogen. Therefore, we investigated haemostatic variables in users of OC containing either 30 μg (35 women) or 50μg (29 women) ethinyl estradiol as compared with non users (64 women) matched for age and smoking status. Mean values of antithrombin activity were significantly lower in 30 γg or 50 μg oestrogen users than in non users (96% and 98% vs 105%, respectively, p<0.001), but they were not significantly different between the two groups of OC users. There was a significant increase in mean values of factor VII antigen in women taking either 30μg or 50μg oestrogen as compared with non users (96% and 101% vs 85%, respectively, p<0.005). Although the difference between both groups of OC users was not significant, a positive linear trend in factor VII levels was observed within the 0-50μg oestrogen range (p <0.001). Mean levels of fibrinogen were slightly higher in 30μg or 50μg oestrogen users than in non users (2.71, 2.66 g/l vs 2.55 g/l, respectively,), but there was no significant difference between the three groups. Mean values of PAI-1 activity were significantly lower in both groups of OC users than in non users (4.89 and 4.63 AU/ml vs 6.47 AU/ml, respectively, p <0.02), but this decrease was not dose-dependent. There was no significant difference in haemostatic variables between 30 μg oestrogen preparations containing either 100μg (13 women), 150μg (3 women) or 200μg (19 women) levonorgestrel. In 50μg oestrogen preparations, the wide range of different types of progestogens did not allow valid assessment of proge- stogens effect. These data provide further evidence for an alteration of blood coagulation and fibrinolysis in OC users within the 30μg-50μg oestrogen range. However, despite a possible dose-dependent effect of oestrogen on factor VII, our results suggest no substantial change in PAI-1 activity and other markers of thrombogenic risk when oestrogen content of combined OC is decreased from 50μg to 30μg. The potential role of progestogens in haemostatic system needs further investigations.
Aurintricarboxylic Acid Reduces Platelet Deposition in Stenosed and Endothelially Injured Rabbit Carotid Arteries more Effectively than other Antiplatelet Interventions
Authors: Golino Palolo , Ragni Massimo , Cirillo Plinio , Pascucci Immacolata , Ezekowitz Michael D , Pawashe Aruna , Scognamiglio Annalisa , Pace Leonardo , Guarino Angela , Chiariello Massimo
Published: July 2018

In the present study we tested the effects of different antithrombotic interventions on platelet deposition in experimentally-stenotic rabbit carotid arteries with endothelial injury. Platelet deposition, quantitated by labeling autologous platelets with 111 In-oxine, was significantly reduced compared to control animals by all interventions tested, i.e., R 68070, a drug with thromboxane A2 synthase and receptor blocking properties, BN 52021, a PAF receptor antagonist, aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (Gp) Ib/von Wille-brand factor (vWf) interaction, AZ-1, a monoclonal antibody against rabbit GPIIb/IIIa, the platelet receptor for fibrinogen, and AP-1, a monoclonal antibody against rabbit tissue factor. ATA was significantly more effective than all the other interventions in reducing platelet deposition in the stenotic vessels. We conclude that inhibition of Gp Ib/vWf interaction may be a more suitable target for antithrombotic therapy under conditions of high shear stress, like those produced in this model.
Induction of Immune Tolerance in a 7-Year-Old Hemophiliac with an Anaphylactoid Inhibitor
Authors: Harper James L , Gill Joan C , Hopp Russell J , Evans John , Haire William D
Published: July 2018

Background: Anaphylactic reactions were a rare complication of low purity VIII concentrates, hut not with high purity VIII concentrates

Case: 7 y/o WM with severe hemophilia A, received only cryoprecipitate and monoclonally purified VIII concentrates; developed post-infusional urticaria. A 2-Bethesda-unit inhibitor was detected. Generalized urticaria and bronchospasm following factor developed as the titer increased. Skin tests demonstrated reactivity to plasma derived VIII, but not recombinant VIII (rhVIII). Attempts at desensitization using rhVIII failed. KLISA revealed an anti-VIIl IgB antibody. He was treated with a modified tolerance regimen using rhVIII starting at 500 U/day with aggressive premedication. The dosage increased by 200 U weekly as tolerated to a maximum of l00U/kg/d without symptoms. Results: His antibody titer decreased rapidly once he started l00U/kg/d. Six months later, the inhibitor was <1 Bethesda unit. Conclusion: Immune tolerance induction using a graduated dosage of rhVIII was successful.
Characterization of a cDNA for Rhesus Monkey Protein C Inhibitor – Evidence for N-Terminal Involvement in Heparin Stimulation
Authors: Radtke Klaus-P , Fernández José A , Villoutreix Bruno O , Greengard Judith S , Griffin John H
Published: July 2018

cDNAs for protein C inhibitor (PCI) were cloned from human and rhesus monkey
1
liver RNAs by reverse transcription and polymerase chain reaction (PCR) amplification. Sequencing showed that rhesus monkey and human PCI cDNAs were 93% identical. Predicted amino acid sequences differed at 26 of 387 residues. Pour of these differences (T352M, N359S, R362K, L3631) were in the reactive center loop that is important for inhibitory specificity, and two were in the N-terminal helix (M8T, E13K) that is implicated in glycosaminoglycan binding. PCI in human or rhesus monkey plasma showed comparable inhibitory activity towards human activated protein C in the presence of 10 U/ml heparin. However, maximal acceleration of the inhibition of activated protein C required 5-fold lower heparin concentration for rhesus monkey than for human plasma, consistent with the interpretation that the additional positive charge (E13K) in a putative-heparin binding region increased the affinity for heparin.