bluuebunny/crossref_metadata_2025 huggingface dataset:
Socially-mediated arousal and contagion within domestic chick broods
Authors: Edgar Joanne L. , Nicol Christine J.
Published: July 2018

Emotional contagion – an underpinning valenced feature of empathy – is made up of simpler, potentially dissociable social processes which can include socially-mediated arousal and behavioural/physiological contagion. Previous studies of emotional contagion have often conflated these processes rather than examining their independent contribution to empathic response. We measured socially-mediated arousal and contagion in 9-week old domestic chicks (n = 19 broods), who were unrelated but raised together from hatching. Pairs of observer chicks were exposed to two conditions in a counterbalanced order: air puff to conspecifics (AP) (during which an air puff was applied to three conspecifics at 30 s intervals) and control with noise of air puff (C) (during which the air puff was directed away from the apparatus at 30 s intervals). Behaviour and surface eye temperature of subjects and observers were measured throughout a 10-min pre-treatment and 10-min treatment period. Subjects and observers responded to AP with increased freezing, and reduced preening and ground pecking. Subjects and observers also showed reduced surface eye temperature - indicative of stress-induced hyperthermia. Subject-Observer behaviour was highly correlated within broods during both C and AP conditions, but with higher overall synchrony during AP. We demonstrate the co-occurrence of socially-mediated behavioural and physiological arousal and contagion; component features of emotional contagion.
Decoding unconstrained arm movements in primates using high-density electrocorticography signals for brain-machine interface use
Authors: Hu Kejia , Jamali Mohsen , Moses Ziev B. , Ortega Carlos A. , Friedman Gabriel N. , Xu Wendong , Williams Ziv M.
Published: July 2018

Motor deficit is among the most debilitating aspects of injury to the central nervous system. Despite ongoing progress in brain-machine interface (BMI) development and in the functional electrical stimulation of muscles and nerves, little is understood about how neural signals in the brain may be used to potentially control movement in one’s own unconstrained paralyzed limb. We recorded from high-density electrocorticography (ECoG) electrode arrays in the ventral premotor cortex (PMv) of a rhesus macaque and used real-time motion tracking techniques to correlate spatial-temporal changes in neural activity with arm movements made towards objects in three-dimensional space at millisecond precision. We found that neural activity from a small number of electrodes within the PMv can be used to accurately predict reach-return movement onset and directionality. Also, whereas higher gamma frequency field activity was more predictive about movement direction during performance, mid-band (beta and low gamma) activity was more predictive of movement prior to onset. We speculate these dual spatiotemporal signals may be used to optimize both planning and execution of movement during natural reaching, with prospective relevance to the future development of neural prosthetics aimed at restoring motor control over one’s own paralyzed limb.
Microalgal Microscale Model for Microalgal Growth Inhibition Evaluation of Marine Natural Products
Authors: Zhao Qing , Chen An-Na , Hu Shun-Xin , Liu Qian , Chen Min , Liu Lu , Shao Chang-Lun , Tang Xue-Xi , Wang Chang-Yun
Published: July 2018

Marine organisms especially sessile invertebrates, such as soft corals, gorgonians and sponges, can survive in the competitive environment mainly relying on their second metabolites with chemoecological effects including allelopathy and algal growth inhibition. It is well known that the microscale models are urgently needed in marine chemoecology assessment to evaluate the algal growth inhibition activity of trace quantity natural products. In this work, a microalgal growth inhibition model was established for microalgal inhibition evaluation of marine natural products with 96-well microplate by automatic fluorescence observation using microplate reader. Subsequently, this model was applied to bioassay-guided isolation and preliminary bioactivity screening of the secondary metabolites from soft corals, gorgonians, sponges and their symbiotic microbes collected from the South China Sea. As a result, fifteen compounds (1‒15) were found to exhibit microalgal growth inhibition activities against at least one of marine microalgae, Karenia mikimotoi, Isochrysis galbana, and Heterosigma akashiwo. Specifically, altersolanol C (13) demonstrated potent activity against K. mikimotoi with the 96h-EC50 value of 1.16 µg/mL, more than four times stronger than that of the positive control K2Cr2O7. It was suggested that the microalgal growth inhibition microscale model is suitable for bioassay-guided isolation and preliminary bioactivity screening of marine natural products.
Nutraceuticals in prostate cancer therapeutic strategies and their neo-adjuvant use in diverse populations
Authors: Reed Dominique , Raina Komal , Agarwal Rajesh
Published: July 2018

Prostate cancer (PCa) is the most frequently diagnosed malignancy and second leading cause of cancer mortality in American males. Notably, men of African descent in the United States and Caribbean have the highest PCa mortality rates compared to men with European ancestry. Although current therapeutics are quite potent and effective, disease resistance, progression to metastasis, therapy-associated toxicities and efficacy-related issues in diverse populations develop over time. Thus, non-toxic and efficacious therapeutic strategies are needed to address these major obstacles for the clinical treatment and management of PCa. In this regard, preclinical and population-based efficacy studies have shown the potential of natural non-toxic nutraceuticals as potent anti-PCa agents. Accordingly, the implementation of nutraceutical intervention and genetic testing in diverse populations might aid in the development and design of precision medicine strategies to reduce the burden of chemotherapy-associated toxicities, suppress disease resistance, and treat both localized and advanced PCa. Consequently, additional large-scale and inclusive clinical studies are required to fully assess efficacy and therapeutic limitations of these agents in PCa. This review discusses the most current clinical research on selected nutraceutical agents and their efficacy in the context of clinico-pathological outcomes and disease susceptibility in diverse PCa clinical and epidemiological studies.
Molecular adaptation in supramolecular self-assembly: brickwall-type phases of indacene-tetrone on silver surfaces
Authors: Kalashnyk Nataliya , Dumur Frédéric , Gigmes Didier , Clair Sylvain
Published: July 2018

Different contrasts are observed via STM in brickwall phases of indacene-tetrone resulting from the adaptation on different epitaxial templates.
Visible-light circular dichroism of colourless chiral organic compounds enabled by interfacial charge-transfer transitions
Authors: Fujisawa Jun-ichi , Kaneko Naohito , Eda Takumi , Hanaya Minoru
Published: July 2018

We report the visible-light circular dichroism (CD) of colourless organic compounds based on interfacial charge-transfer (ICT) transitions with TiO2 nanoparticles.
A photo-responsive poly(amide–triazole) physical organogel bearing azobenzene residues in the main chain
Authors: Wang Huai-Zhen , Chow Hak-Fun
Published: July 2018

The synthesis of a click poly(amide–triazole) bearing multiple azobenzene units along the main chain was reported.
Alkaline-earth metal based MOFs with second scale long-lasting phosphor behavior
Authors: Briones David , Leo Pedro , Cepeda Javier , Orcajo Gisela , Calleja Guillermo , Sanz Raúl , Rodríguez-Diéguez Antonio , Martínez Fernando
Published: July 2018

Three MOFs based on alkaline-earth metals and aromatic carboxylate linkers show blue fluorescence that turns into green long-lasting phosphorescence.
Insight into the enhanced photocatalytic activity of SrTiO3 in the presence of a (Ni, V/Nb/Ta/Sb) pair
Authors: Modak Brindaban , Ghosh Swapan K.
Published: July 2018

Present study explored the effect of codoping of V, Nb, Ta, and Sb into Ni-doped SrTiO3 to enhance its photocatalytic activity under visible light.
RGO-functionalized polymer nanofibrous membrane with exceptional surface activity and ultra-low airflow resistance for PM2.5 filtration
Authors: Zhang Peng , Wan Dongyang , Zhang Zhenyi , Wang Guodong , Hu Junhua , Shao Guosheng
Published: July 2018

RGO-functionalized polymer nanofibrous membrane is developed through an electrospinning technique, which exhibits the exceptional surface activity and ultra-low airflow resistance for PM2.5 filtration.
The gut microbiota urolithin metabotypes revisited: the human metabolism of ellagic acid is mainly determined by aging
Authors: Cortés-Martín A. , García-Villalba R. , González-Sarrías A. , Romo-Vaquero M. , Loria-Kohen V. , Ramírez-de-Molina A. , Tomás-Barberán F. A. , Selma M. V. , Espín J. C.
Published: July 2018

Human urolithin gut microbiota metabotypes are mainly determined by aging.
Quantitative and multiplex microRNA assays from unprocessed cells in isolated nanoliter well arrays
Authors: Tentori Augusto M. , Nagarajan Maxwell B. , Kim Jae Jung , Zhang Wen Cai , Slack Frank J. , Doyle Patrick S.
Published: July 2018

This platform utilizes functionalized hydrogel posts contained within isolated nanoliter well reactors for quantitative and multiplex microRNA assays directly from unprocessed cell samples without needing prior nucleic acid extraction.
Synthesis of new spiro pyrrole/pyrrolizine/thiazole derivatives via (3+2) cycloaddition reactions
Authors: Mali Prakash R. , Khomane Navnath B. , Sridhar B. , Meshram H. M. , Likhar Pravin R.
Published: July 2018

An efficient one-pot multi-component protocol has been developed for the synthesis of novel spiro-fused pyrrole/pyrrolizine/thiazole derivatives using (3+2) cycloaddition reactions; all products were obtained in moderate to excellent yields and synthesized from commercially available starting materials.
Room-temperature ferroelectricity and a switchable diode effect in two-dimensional α-In2Se3 thin layers
Authors: Wan Siyuan , Li Yue , Li Wei , Mao Xiaoyu , Zhu Wenguang , Zeng Hualing
Published: July 2018

A switchable diode based on room-temperature two-dimensional ferroelectric α-In2Se3 thin layers.
A systematic study of the co-solvent effect for an all-organic redox flow battery
Authors: Wang Xiang , Xing Xueqi , Huo Yongjie , Zhao Yicheng , Li Yongdan
Published: July 2018

BP/DBB are used as active species in AORFB. The solubility of DBB is increased by co-solvents.
Molecular dynamics simulation of droplet nucleation and growth on a rough surface: revealing the microscopic mechanism of the flooding mode
Authors: Niu Dong , Tang GuiHua
Published: July 2018

Droplet nucleation and growth have a significant influence on dropwise condensation heat transfer.
Bayberry tannin immobilized bovine serum albumin nanospheres: characterization, irradiation stability and selective removal of uranyl ions from radioactive wastewater
Authors: Yu Jie , Luo Xuegang , Liu Bo , Zhou Jian , Feng Jian , Zhu Wenkun , Wang Shanlin , Zhang Yongde , Lin Xiaoyan , Chen Ping
Published: July 2018

A novel bayberry tannin immobilized BSA–BT-NS adsorbent with excellent adsorption capacity and high selectivity for UO22+.
Solvent treatment: the formation mechanism of advanced porous membranes for flow batteries
Authors: Lu Wenjing , Qiao Lin , Dai Qing , Zhang Huamin , Li Xianfeng
Published: July 2018

Advanced porous membranes for flow batteries were successfully prepared by the adjustment of process parameters during solvent treatment.
Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways
Authors: Dimasuay Kris Genelyn , Sanchez Amelia , Schaefer Niccolette , Polanco Jorge , Ferrington Deborah A. , Chu Hong Wei
Published: July 2018

Rhinovirus (RV) infection is involved in acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). RV primarily infects upper and lower airway epithelium. Immunoproteasomes (IP) are proteolytic machineries with multiple functions including the regulation of MHC class I antigen processing during viral infection. However, the role of IP in RV infection has not been explored. We sought to investigate the expression and function of IP during airway RV infection. Primary human tracheobronchial epithelial (HTBE) cells were cultured at air–liquid interface (ALI) and treated with RV16, RV1B, or interferon (IFN)-λ in the absence or presence of an IP inhibitor (ONX-0914). IP gene (i.e. LMP2) deficient mouse tracheal epithelial cells (mTECs) were cultured for the mechanistic studies. LMP2-deficient mouse model was used to define the in vivo role of IP in RV infection. IP subunits LMP2 and LMP7, antiviral genes MX1 and OAS1 and viral load were measured. Both RV16 and RV1B significantly increased the expression of LMP2 and LMP7 mRNA and proteins, and IFN-λ mRNA in HTBE cells. ONX-0914 down-regulated MX1 and OAS1, and increased RV16 load in HTBE cells. LMP2-deficient mTECs showed a significant increase in RV1B load compared with the wild-type (WT) cells. LMP2-deficient (compared with WT) mice increased viral load and neutrophils in bronchoalveolar lavage (BAL) fluid after 24 h of RV1B infection. Mechanistically, IFN-λ induction by RV infection contributed to LMP2 and LMP7 up-regulation in HTBE cells. Our data suggest that IP are induced during airway RV infection, which in turn may serve as an antiviral and anti-inflammatory mechanism.
Young Children's Structure Production: A Revision of the Index of Productive Syntax
Authors: Altenberg Evelyn P. , Roberts Jenny A. , Scarborough Hollis S.
Published: July 2018

Purpose

The Index of Productive Syntax (IPSyn; Scarborough, 1990) is widely used to measure syntax production in young children. The goal of this article is to promote greater clarity and consistency in machine and hand scoring by presenting a revised version of the IPSyn (IPSyn-R) and comparing it with the original IPSyn (IPSyn-O).

Method

Longitudinal syntax production in 10 30- and 42-month-old typically developing children drawn from the Child Language Data Exchange System (MacWhinney, 2000) Weismer corpus was examined, using both the IPSyn-O and the IPSyn-R.

Results

The IPSyn-R provided nearly identical scores to the IPSyn-O with the exception of scores affected primarily by 1 modified noun phrase structure. Structures ranked as more advanced were produced less frequently. The results also reveal which of the IPSyn-R's 59 structures were most and least likely to be produced by this sample at these ages.

Conclusions

The qualitative and quantitative differences between the IPSyn-O and the IPSyn-R are relatively minor. The IPSyn-R can make it easier to score the IPSyn, both by clinicians and researchers, and facilitate the IPSyn's move to machine scoring of language samples.
Wege zu einer „Angehörigenfreundlichen Intensivstation“
Authors: Voß Stefanie
Published: July 2018

Die Besuchszeiten sind auf den meisten Intensivstationen streng reglementiert. Das widerspricht nicht nur den Bedürfnissen der Angehörigen, sondern wirkt sich auch negativ auf den Genesungsprozess der Patienten aus. Dabei ist es gar nicht so schwierig, die Besuchsregelungen flexibel und individuell zu gestalten.
Model of Human Occupation (MOHO) – Praktisch angewandt
Authors: Kaldewei Nicole
Published: July 2018

Das MOHO ist vielen Ergotherapeuten als Inhaltsmodell und durch Assessments wie das Child Occupational Self Assessment (COSA) oder das Worker Role Interview (WRI) bekannt. 2017 erschien die englisch-sprachige Neuauflage. Zu den Neuentwicklungen gehört unter anderem die detaillierte Betrachtung der Umwelt des Klienten. Das Klientenbeispiel dieses Artikels nimmt in erster Linie Bezug auf diese Neuerungen.
Duration of Oral Anticoagulant Therapy after Proximal Deep Vein Thrombosis: a Decision Analysis
Authors: Sarasin François P , Bounameaux Henri
Published: July 2018

The optimal duration of oral anticoagulant therapy following proximal deep vein thrombosis (DVT) in the lower limbs remains controversial. To compare the risk benefit tradeoffs for different treatment durations (6 to 24 weeks) we constructed a Markov-based decision analysis model which explicitly balances the time-dependent declining risk of recurrent thrombosis and pulmonary embolism against the risk of major hemorrhagic complications. Specifically, we determined the threshold below which the risk of recurrent DVT exceeds the risk of major hemorrhage if anticoagulant therapy is discontinued, and above which the benefits provided by oral anticoagulants are outweighed by their risk.

Our model shows that for patients with a low hemorrhagic risk (0.5%/month), the benefit yielded by oral anticoagulants breaks off beyond the 4th month of therapy, while patients with moderate (1%/month) to high (2%/month) bleeding risk will no longer benefit from the therapy after 3 or 2.5 months, respectively.

In conclusion, our model supports the validity of the usually recommended duration of 3 months of oral anticoagulation after proximal vein thrombosis in the lower limbs, but suggests that this duration should be modulated between 2.5 and 4 months depending upon individual bleeding risk. Since clinical trials can hardly handle the complexity of the addressed issue, such a model may prove very helpful in daily clinical practice.
Inhibition of In Vitro Clot Growth by r-Hirudin Is More Effective and Longer Sustained than by an Analogous Peptide
Authors: Römisch Jürgen , Stöhr Hans-Arnold , Stauß Harald , Koschinsky Rainer , Stüber Werner , Pâques Eric-Paul
Published: July 2018

The specific thrombin inhibitors r-hirudin and a synthetic peptide (I)
D
-FPRP(G)4-NGDFEEIPEEYL were compared in in vitro tests, r-hirudin proved to be the superior compound with respect to inhibition of amidolytic small substrate turnover that is catalysed by soluble and immobilised thrombin as well as to inhibition of fibrinogen activation. In an in vitro clot model significantly higher molar concentrations of peptide I are needed to achieve fibrin bound thrombin inhibition equivalent to that of r-hirudin. Stable complexes consisting of thrombin and hirudin oppose labile complexes containing the synthetic peptide. The latter leads to a regaining of thrombin activity with subsequent additional fibrin accretion. Analyses of the mixtures of thrombin and peptide I display a time dependent release of amino-terminal
D
-FPR peptide (III) exhibiting, similar to the residual fragment (peptide II), only weak inhibitory activity. Peptide I and the carboxy-terminal fragment induce, within a certain concentration range, an increase in thrombin activity and clot growth.
Humic Acid Induces Expression of Tissue Factor by Cultured Endothelial Cells: Regulation by Cytosolic Calcium and Protein Kinase C
Authors: Yang Hsin-Ling , Lu Fung-Jou , Wung Shu-Li , Chiu Hui-Chong
Published: July 2018

Blackfoot disease is a thrombotic peripheral vascular disease causally related to the fluorescent humic acid (HA) found in the drinking water of wells in endemic areas in Taiwan. In this study we examined the effect of HA on tissue factor (TF) expression by vascular endothelial cells.

Incubation of cultured human umbilical vein endothelial cells (HUVEC) with HA isolated from endemic area drinking water or with a synthetic humic acid polymer (SHA), resulted in enhanced cell surface expression of TF activity by HUVEC. The intracellular calcium level ([Ca24]i) was measured using a calcium-specific fluorescent probe, fura 2. Changes in [Ca24]i level were followed and quantitatively analyzed by spectrofluorometric microscopy, after incubation of the fura 2-loaded HUVEC with HA or SHA in a medium containing 1.8 mM CaCl2. Both HA and SHA increased [Ca2+]i in the presence of extracellular calcium ions, but not in their absence, indicating that influx of extracellular Ca2+ occurred during incubation of HUVEC with HA or SHA. Verapamil, a potent calcium channel blocker, did not abolish the enhancement of [Ca24]i induced by HA or SHA, indicating that specific calcium channels may not be involved in the HA/SHA-induced elevation of [Ca24]i. The elevated [Ca24]i level induced by HA or SHA returned to basal level following removal of HA or SHA and incubation of the washed cells in medium containing 1.8 mM CaCl2. All these changes occurred in the absence of significant cytotoxic effects. The HA/SHA-induced enhancement of cell surface TF activity was inhibited by a specific inhibitor of protein kinase C, H7, suggesting that protein kinase C is involved in the process leading to the enhanced expression of TF activity induced by HA or SHA.

In conclusion, this study demonstrates that HA and SHA enhance cell surface expression of TF activity by permeabilization of the cell membrane to extracellular Ca24 ions, leading to elevation of [Ca2+]i that functions as a second messenger to activate protein kinase C, leading finally to enhanced cell surface TF expression. Enhancement of vascular endothelial cell surface TF activity by HA may play a role in the HA-induced thrombotic vascular disorders of Blackfoot disease.
Platelet-Bound Prekallikrein Promotes Pro-Urokinase-Induced Clot Lysis: A Mechanism for Targeting the Factor XII Dependent Intrinsic Pathway of Fibrinolysis
Authors: Loza Jean-Pierre , Gurewich Victor , Johnstone Michael , Pannell Ralph
Published: July 2018

Clots formed from platelet rich plasma were found to be lysed more readily by low concentrations of pro-urokinase (pro-UK) than clots formed from platelet poor plasma. This was not a non-specific effect since the reverse occurred with tissue plasminogen activator. A mechanical explanation due to platelet-mediated clot retraction was excluded by experiments in which retraction was inhibited with cyto-chalasin B. Therefore, a platelet-mediated enzymatic mechanism was postulated to explain the promotion of fibrinolysis. Casein autography of isolated platelets revealed a ≈ 90 kDa band of activity which comigrated with plasma prekallikrein (PK)/kallikrein, a known activator of pro-UK. Furthermore, treatment of platelets with plasma PK activator (PPA), consisting essentially of factor XIIa, induced activation of pro-UK and of chromomgenic substrate for kallikrein (S-2302). This activity corresponded to approximately 40-200 pM kallikrein per 10
8 washed and gel filtered platelets per ml. The activation of pro-UK by PPA-pretreated platelets was dose-dependent and inhibited by soybean trypsin inhibitor but not by bdellin, a specific inhibitor of plasmin, nor by the corn inhibitor of factor XIIa. Kinetic analysis of pro-UK activation by kallikrein showed promotion of the reaction by platelets. The KM
of the reaction was reduced by platelets by ≈ 7-fold, while the kcat
was essentially unchanged. In conclusion, PK was shown to be tightly associated with platelets where it can be activated by factor XIIa during clotting. The activation of pro-UK by platelet-bound kallikrein provides an explanation for the observed platelet mediated promotion of pro-UK-induced clot lysis. Since pro-UK and plasminogen have also been shown to be associated with platelets, the present findings suggest a mechanism by which the factor Xlla-dependent intrinsic pathway of fibrinolysis can be localized and targeted to a thrombus.
A Comparative Study of Prothrombinase and Thrombin Inhibitors in a Novel Rabbit Model of Non-Occlusive Deep Vein Thrombosis
Authors: Hollenbach Stan , Sinha Uma , Lin Pei-Hua , Needham Kathy , Frey Lisa , Hancock Tom , Wong Arnold , Wolf David
Published: July 2018

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.
Effects of Recombinant Human Soluble Thrombomodulin (rhs-TM) on a Rat Model of Disseminated Intravascular Coagulation with Decreased Levels of Plasma Antithrombin III
Authors: Aoki Yoshikazu , Ohishi Rika , Takei Ryoichi , Matsuzaki Osamu , Mohri Mitsunobu , Saitoh Ken-ichi , Gomi Komakazu , Sugihara Taisuke , Kiyota Takao , Yamamoto Shuji , Ishida Torao , Maruyama Ikuro
Published: July 2018

We reported that recombinant human soluble thrombomodulin (rhs- TM) is effective for disseminated intravascular coagulation (DIC) in vivo, in mice and rats. In the present work, we investigated the effects of decreased plasma antithrombin III (ATIII) levels on anticoagulant effects of rhs-TM, as compared to findings with heparin, of which effect is lowered by the decreased plasma ATIII levels in patients with DIC. Rat plasma ATIII levels decreased when we mixed plasma with anti-rat ATIII antibody and the potential of heparin to prolong APTT or PT was markedly diminished. The potential of rhs-TM to prolong APTT and PT was not affected. In rats injected with anti-rat ATIII antibody, plasma ATIII levels decreased immediately. When the rats were infused with tissue factor (TF), DIC was induced. At doses of rhs-TM and heparin which were equally effective at inhibiting the decrease in platelet count and fibrinogen level in cuntiol rats treated with TF, only rhs-TM remained effective in preventing DIC in rats with reduced ATIII levels. Heparin was not effective, when administered to these rats with reduced ATIII levels. Therefore, rhs-TM effectively inhibits coagulation independent of ATIII levels, in contrast to heparin, which depends on the ATIII level.
Is Heparin the Ideal Anticoagulant for Cardiopulmonary Bypass? Dermatan Sulphate May Be an Alternate Choice
Authors: Brister Stephanie J , Ofosu Frederick A , Heigenhauser George J F , Gianese Francesco , Buchanan Michael R
Published: July 2018

Performance of cardiopulmonary bypass (CPB) during cardiac surgery requires the administration of high dose heparin to prevent CPB pump occlusion. However, this heparin use is associated with bleeding side-effects. Moreover, at the end of CPB, the heparin must be neutralized with protamine sulphate, which is also associated with adverse side-effects. A number of recent studies suggest that dermatan sulphate may be useful as an alternate anticoagulant to heparin. We determined whether CPB could be performed using dermatan sulphate instead of heparin, in an adult pig CPB model. When heparin was used, a high dose (> 200 U/kg, which generated > 3 anti-thrombin U/ml of plasma), was required to perform successful CPB and to maintain CPB pump patency. This dose was associated with a post CPB bleeding of ≈ 600 ml/2h. in contrast, successful CPB could be achieved when the pigs were given lower doses of dermatan sulphate than heparin, which in turn, were associated with less bleeding. We conclude that dermatan sulphate may be an alternate anticoagulant for cardiac surgery
Activation and Inactivation of Human Protein C by Plasmin
Authors: Váradi Katalin , Philapitsch Anton , Santa Thomas , Schwarz Hans Peter
Published: July 2018

Transient procoagulant states resulting in failure of recanalization or rethrombosis of the reperfused artery during thrombolytic therapy might be due to an inhibitory effect of plasmin on the anticoagulant properties of protein C. We therefore studied the effect of plasmin on protein C (PC) and activated protein C (APC) using purified human proteins.

Incubation of 70 nM purified human PC with 40-400 nM human plasmin resulted in rapid activation and subsequent inactivation of PC as measured by amidolytic and anticoagulant assays. The rates of activation and inactivation were dependent on the concentration of plasmin. Lower concentrations of plasmin resulted in higher peaks of generated APC and more sustained activity, while at higher concentrations, both activation and inactivation were more rapid. Anticoagulant activity appeared more sensitive to inactivation by plasmin than amidolytic activity; e. g., while amidolytic activity reached a maximum of 13.8 nM in 6 min and declined to approximately 6 nM after 30 min, anticoagulant activity reached its maximum of only 1.4 nM within 30 s and completely disappeared within 90 s.

Plasmin rapidly destroyed both the anticoagulant and amidolytic activity of purified APC, with second order rate constants of 2.8 × 105 M−1 s−1 and 1.2 × 104 M−1 −1, respectively, for 70 nM APC. The rates of activation and subsequent inactivation were slowed by the presence of CaCl2. The second order rate constant of inactivation of APC amidolytic activity decreased to 6.6 × 103 M−1 s−1 in the presence of 5 mM CaCl2. Proteolytic degradation of both PC and APC corresponding to the loss of amidolytic activity was demonstrated on SDS-PAGE using 125I-labelled proteins. When normal human plasma was incubated with plasmin or streptokinase a substantial loss of PC anticoagulant activity was observed.

These results in vitro suggest that plasmin modulates the anticoagulant properties of protein C in a way that might be of relevance for the success of fibrinolytic therapy.
Aprotinin Could Promote Arterial Thrombosis in Pigs: a Prospective Randomized, Blind Study
Authors: Samama Ch M , Mazoyer E , Bruneval P , Ciostek P , Bonnin Ph , Bonneau M , Roussi J , Bailliart O , Pignaud G , Viars P , Caen J P , Drouet L O
Published: July 2018

Haemostatic properties of aprotinin could be associated with an increased risk of thrombosis. A randomized, blinded study was conducted to consider the potential thrombogenicity of aprotinin, using the Fobs’ model on femoral arteries in 12 pigs. The flow variations were measured by a pulsed Doppler in anaesthetised animals. Ear immersion bleeding time was performed. During the first part of the study, a stenosis was performed successively on both femoral arteries, each for a period of 30 min, without prior injury, to assess the integrity of the vessel, and to check that the arteries did not develop cyclic flow reductions (CFR), permanent cessation of flow (PCF) or partial thrombosis, when a stenosis is applied. Then the clamp was released and a bolus of placebo (saline), or aprotinin (4 millions KIU, followed by a continuous infusion of 1 million KIU · h−1), was administered. At the end of the bolus, the second part of the study began. Stenosis was applied to the arteries. If CRF, PCF, or partial thrombosis were observed without prior injury then the infused drug (aprotinin or saline) was considered a prothrombotic drug, and the opposite artery was studied. For each animal, right and left femoral artery segments were fixed and studied (morphologic study). Eighteen arteries were studied. In the aprotinin group, 6 arteries out of 8 developed an unexpected thrombosis, as compared with only 2 out of 10 arteries in the control group (p = 0.02). The morphologic study confirmed the occurrence of thrombosis in 4 out of 7 arteries in the aprotinin group, as compared with only 1 out of 9 in the control group. The ear immersion bleeding time was not different in either group. No difference could be demonstrated with regard to the values of activated partial thromboplastin time, prothrombin time and fibrinogen.

Aprotinin may have promoted the development of thrombosis in the pig.
Adjusted Versus Fixed Doses of the Low-Molecular-Weight Heparin Fragmin in the Treatment of Deep Vein Thrombosis
Authors: Alhenc-Gelas M , Guernic C Jestin-Le , Vitoux J F , Kher A , Aiach M , Fiessinger J N ,   Fragmin-Study Group
Published: July 2018

Treatment monitoring based on a laboratory parameter increases the efficacy and safety of standard heparin therapy, but it is not known if this also applies to low-molecular-weight heparin (LMWH) therapy of acute deep vein thrombosis (DVT). In a prospective randomized trial involving 122 consecutive patients, group A (58 patients) received a weight adjusted dose of Fragmin (100 IU/kg) subcutaneously twice a day throughout the treatment period (10 days ± 1), while in group B (64 patients) the dosage was based on the results of an anti factor Xa (anti Xa) amidolytic assay to obtain a target concentration from 0.5 to 1 IU/ml. AntiXa and antithrombin activities were also measured retrospectively on frozen plasma from all patients. The two regimens were comparable in terms of hemorrhagic complications (4 in group A and 3 in group B). Bilateral ascending phlebography was performed before inclusion and at the end of LMWH treatment. Treatment efficacy, based on Marder’s score, did not differ between the two groups (p = 0.3). Dosage adjustment to between 0.5 to 1IU anti-Xa/ml does not therefore appear to improve the efficacy or safety of LMWH tieatment. However, correlations between the change in Marder’s score and both anti-Xa (p <0.001) and antithrombin activity (p <0.001) were observed, suggesting a relationship between the degree of FXa or thrombin inhibition and antithrombotic activity.
Relationship of Tissue Factor Pathway Inhibitor Activity to Plasma Lipoproteins and Myocardial Infarction at a Young Age
Authors: Moor Elisabeth , Hamsten Anders , Karpe Fredrik , Båvenholm Peter , Blombäck Margareta , Silveira Angela
Published: July 2018

Tissue factor pathway inhibitor (TFPI) activity was quantified in two cohorts of young male post-infarction patients and in population-based control subjects to explore the relationships between TFPI activity and plasma lipoproteins and to address the issue of coordinate regulation of factor VII and TFPI in hyperlipidaemia and premature coronary heart disease (CHD). Participants were investigated in the fasting state and after an oral fat load. Basal TFPI activity and factor VII antigen (VIIag) levels were found to be increased in the patients (TFPI activity 1.25 ± 0.23 vs 1.17 ± 0.20 U/ml, p <0.05; VIIag 537.7 ± 127.7 vs 479.4 ± 93.4 ng/ml, p <0.001). The parallel increase was accounted for by patients with hypertriglyceridaemic lipoprotein phenotypes. In contrast, the level of activated factor VII (VIIa) neither differed significantly between patients and controls, nor between patients with different lipoprotein phenotypes. The elevated TFPI activity in the patients was closely associated with the plasma level of dense low density lipoprotein (LDL) particles (r = 0.46, p <0.001) and with the plasma concentration of the small, dense high density lipoprotein (HDL) subspecies HDL3b (r = 0.34, p <0.01).
Apolipoprotein(a), Fibrinopeptide A and Carotid Atherosclerosis in Middle-Aged Men
Authors: Rankinen Tuomo , Väisänen Sari , Mercuri Michele , Rauramaa Rainer
Published: July 2018

The association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% Cl 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% Cl 1.73; 2.09)] apo(a) quartile. The difference remained (p=0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases.
Thrombomodulin Induction by All-trans Retinoic Acid Is Independent of HL-60 Cells Differentiation to Neutrophilic Cells
Authors: Kizaki Keiichiro , Ishii Hidemi , Horie Shuichi , Kazama Mutsuyoshi
Published: July 2018

The expression of thrombomodulin (TM), an antithrombotic factor, was investigated during neutrophilic differentiation of the HL-60 human myeloblastic cell line treated with d\\-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Differentiation of the cells into neutrophilic cells progressed in a time- and dose-dependent fashion with ATRA or DMSO, as confirmed by the characteristic appearance of nitroblue tetrazolium (NBT) reduction and phagocytic activities, without induction of nonspecific esterase activity. TM antigen and cofactor activity for thrombin-dependent protein C activation were not detected in untreated HL-60 cells and the cells cultured with DMSO, but were expressed in a time-dependent manner in the cells cultured with ATRA. The level of TM expression in the HL-60 cells was not dose-dependent on ATRA concentrations, but maximum TM expression was obtained at 10−7 M ATRA. TM expression levels decreased in cells cultured with greater than 10−6 M ATRA, although the extent of cell differentiation into neutrophilic cells progressed at the higher ATRA concentrations. Since the TM antigen levels in the ATRA-treated cells also paralleled the TM mRNA levels, the data suggests that TM induction in the HL-60 cells cultured with ATRA reflected the levels of TM biosynthesis and was independent of HL-60 differentiation into neutrophilic cells. It was postulated that the appearance of TM with cofactor activity in neutrophilic cells differentiated from leukemic cells may contribute to prevention of vascular thrombosis in differentiation therapy of patients with acute promyelocytic leukemia by ATRA.
Plasma D-Dimer as a Marker for Postoperative Deep Venous Thrombosis
Authors: Dunn Irene D , Hui Anthony C W , Triffitt Paul D , Crozier Ann E C , Gregg Paul J , Sinclair Marie E , Lynn Armstrong A , Mitchell Vivian E
Published: July 2018

Plasma levels of D-dimer have been found useful as a marker of deep venous thrombosis in those patients in whom thrombosis is suspected, but their usefulness in postoperative screening is less clear. We have investigated the relationship of D-dimer to deep venous thrombosis in 90 patients after total hip and knee arthroplasty. From the first postoperative day the D-dimer levels were found to be highly significantly raised in patients with deep venous thrombosis. A combined result over the first six postoperative days in excess of 1200ng/ml correlated with thrombosis with a specificity of 100%, sensitivity of 45%, positive predictive value of 60%, and negative predictive value of 100%. However, individual estimations were not discriminatory.
French Multicentric Evaluation of Recombinant Tissue Factor (Recombiplastin) for Determination of Prothrombin Time
Authors: Roussi J , Drouet L , Samama M , Sié P , Bal C , Boudaoud L , Cazenave J P , Denninger M H , Droule Ch , Horellou M H , Levy G , Mazoyer E , Sampol J , Schved J F , Vergnes C
Published: July 2018

Recombiplastin, a recombinant a human tissue factor, elaborated by Ortho Diagnostic Systems, produced by Baculovirus and relipidated with highly purified phospholipids, was tested as a new reagent for determining prothrombin time (PT) in a French multicentric study. Its intralaboratory- performances, including sensitivity, repeatability, reproducibility and stability, were explored to establish whether its use would reduce the interlaboratory dispersion of PT values, and therefore improve the standardization of oral anticoagulant treatment.

The 9 university hospital hematology laboratories involved in this study used the same type of instrument (KC 10). For 10 consecutive days, they determined PTS on a normal plasma pool, plasma dilutions of 1/2, 1/3 and 1/8, 3 identical lyophilized calibrated plasmas, as well as plasmas from 20 normal subjects, 50 patients on oral anticoagulant therapy with Recombiplastin which has an International Sensitivity Index (ISI) of 1, and 2 commercial thromboplastin extracts (ISI #1 or 2). In the patients on anticoagulants, factors VII, X and V were measured when results were conflicting.

The intra and interlaboratory reproducibilities of Recombiplastin, calculated on the basis of either PTS expressed in seconds, or of the International Normalized Ratio (INR), were good, with coefficients of variation (CV) similar to those observed with the 5 other reagents used by the different laboratories (2% <CV <8%).

The stability of Recombiplastin was excellent, with no variation in PT after 72 h of incubation at 37° C.

A normal PT of 12 s was obtained with Recombiplastin, similar to the values found for the reagents with ISI #2. In the patients on anticoagulants, Recombiplastin gave the longest coagulation times (PTRecombipiastin = 64.2 s vs PTNeoPlastin = 32.8 s, and PTThromborel = 54.4 s). These results suggest that Recombiplastin is highly sensitive to the changes in coagulation induced by anticoagulants. Recombiplastin was more sensitive to factor VII deficiency than any of the other reagents, even those with ISI #1.

The coefficients of correlation between the INRS calculated on the basis of the PTS obtained with Recombiplastin and the INRS based on the PTS for other thromboplastins, were satisfactory (0.85 <R <0.95) but a breakpoint in the slope of the regression curves was observed when INR >4. This observation requires further investigation, particularly in connection with the exact ISI values for Recombiplastin and the other thromboplastins used in this study.

In conclusion, Recombiplastin is stable and sensitive and gives accurate reproducible results. However, the behavior of Recombiplastin is slightly different from that of the commercial reagents whether their ISI is 1 or 2, and its use did not reduce the interlaboratory dispersion of PT values.
The Platelet Cytoskeleton
Authors: Fox Joan E B
Published: July 2018

The platelet cytoskeleton contains two actin filament-based components. One is the cytoplasmic actin filaments which fill the cytoplasm and mediate contractile events. The other is the membrane skeleton, which coats the plasma membrane and regulates properties of the membrane such as its contours and stability. In the unstimulated platelet, only 30-40% of the actin is polymerized into filaments; the rest is thought to be prevented from polymerizing by the association of thymosin β4 with monomeric actin and by the association of gelsolin with the barbed ends of pre-existing actin filaments. When platelets are activated, there is a rapid increase in actin polymerization; new filaments fill the extending filopodia and form a network at the periphery of the platelet. As a result of activation, myosin binds to cytoplasmic actin filaments, causing them to move towards the center of the platelet. As platelets aggregate, additional cytoskeletal reorganizations occur: GP Ilb-IIIa associates with adhesive ligand in a platelet aggregate; this results in the association of GP Ilb-IIIa, membrane skeleton proteins, and signaling molecules with cytoplasmic actin. Future studies should help to elucidate the significance of the cytoskeleton in regulating signal transduction events in platelets.
Antithrombotic Activity of Bay u3405, a Thromboxane A2-Antagonist, in Patients with Dacron Aortic Grafts: a Random Controlled Clinical Trial
Authors: Pieters H , Roodt J P , Badenhorst P N , van Wyk V , Schall R , Lötter M G , Hundt H K L , Nel C J C
Published: July 2018

Twelve patients with Dacron aortic grafts participated in a placebo controlled, crossover trial to investigate the effect of Bay u3405, a thromboxane A2-receptor antagonist, on graft throm-bogenicity. During each treatment period (seven days, Bay u3405 or placebo), 111In-platelet survival and platelet deposition on the grafts were measured daily by γ-camera imaging and blood radioactivity analysis. Bay u3405 substantially reduced the deposition of platelets and the thrombogenic index, while platelet survival remained unchanged. The ex vivo platelet aggregation response to ADP and epinephrine was significantly inhibited. The bleeding time increased slightly but not to any clinically relevant extent, and no adverse side effects were recorded.

Bay u3405 seems to be a safe and effective drug for the inhibition of platelet deposition on aortic Dacron grafts. The use of quantitative imaging techniques is also more sensitive than the measurement of platelet survival for the assessment of antiplatelet drug efficacy in patients with aortic grafts.
Evidence for the Regulation of Urokinase and Tissue Type Plasminogen Activators by the Serpin, Protein C Inhibitor, in Semen and Blood Plasma
Authors: España Francisco , Estellés Amparo , Fernández Pedro J , Gilabert Juan , Sánchez-Cuenca Jaime , Griffin John H
Published: July 2018

Since the serine protease inhibitor, protein C inhibitor (PCI), is present in seminal plasma at ≈3 μM, complexes of PCI with urokinase (uPA) and tissue type (tPA) plasminogen activator were quantitated using sandwich enzyme-linked immunosorbent assays (ELISA’s). Seminal plasma (N = 10) collected in the absence of extrinsic inhibitors had a mean of 25 ± 5 ng/ml uPA: PCI, 76 ± 23 ng/ml tPA: PCI, and 4 ± 2 ng/ml of tPA complexes with plasminogen activator inhibitor-1 (tPA:PAI-l). 93% of the uPA and 17% of the tPA antigen in seminal plasma was in complex with PCI and, when complexation was inhibited by collecting semen into an 1,10-phenanthrolinium solution, 33% of the uPA and 7% of the tPA was complexed to PCI. Urine (N = 10) contained 4 ± 1 ng/ml uPA:PCI. In purified system, complexation of uPA and tPA to PCI paralleled the inhibition of the enzymes. In vitro studies in blood and seminal plasma showed that heparin stimulated complexation of uPA and tPA with PCI, suggesting that negatively charged glycosaminoglycans in blood vessels and in the reproductive system may regulate PCI reactions with uPA and tPA. These results suggest that PCI is a physiologic regulator of uPA and tPA in male reproductive tissues and raises questions about a potential role of PCI in human fertility and in uPA-dependent cell invasiveness.
Requirement for Both D Domains of the Propolypeptide in von Willebrand Factor Muitimerization and Storage
Authors: Journet Agnès M , Saffaripour Simin , Wagner Denisa D
Published: July 2018

Biosynthesis of the adhesive glycoprotein von Willebrand factor (vWf) by endothelial cells results in constitutive secretion of small multimers and storage of the largest multimers in rodshaped granules called Weibel-Palade bodies. This pattern is reproduced by expression of pro-vWf in heterologous cells with a regulated pathway of secretion, that store the recombinant protein in similar elongated granules. In these cells, deletion of the vWf prosequence prevents vWf storage. The prosequence, composed of two homologous domains (D1 and D2), actively participates in vWf multimer formation as well. We expressed deletion mutants lacking either the D1 domain (D2vWf) or the D2 domain (D1vWf) in various cell lines to analyze the relative importance of each domain in vWf muitimerization and storage. Both proteins were secreted efficiently without being retained in the endoplasmic reticulum. Despite this, neither multimerized past the dimer stage and they were not stored. We conclude that several segments of the prosequence are jointly involved in vWf muitimerization and storage.