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https://www.readbyqxmd.com/read/28231553/a-reusable-aptasensor-of-thrombin-based-on-dna-machine-employing-resonance-light-scattering-technique
#1
Yining Hou, Jifeng Liu, Min Hong, Xia Li, Yanhua Ma, Qiaoli Yue, Chen-Zhong Li
The design of molecular nanodevices attracted great interest in these years. Herein, a reusable, sensitive and specific aptasensor was constructed based on an extension-contraction movement of DNA interconversion for the application of human thrombin detection. The present biosensor was based on resonance light scattering (RLS) using magnetic nanoparticles (MNPs) as the RLS probe. MNPs coated with streptavidin can combine with biotin labeled thrombin aptamers. The combined nanoparticles composite is monodispersed in aqueous medium...
February 20, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28230176/antithrombotic-therapy-for-patients-with-stemi-undergoing-primary-pci
#2
REVIEW
Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo
Antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Intravenous anticoagulant drugs available for PPCI include the indirect thrombin inhibitors unfractionated heparin and low-molecular-weight heparin, and the direct thrombin inhibitor bivalirudin. Intravenous antiplatelet drugs mainly include glycoprotein IIb/IIIa inhibitors and the P2Y12-receptor inhibitor cangrelor...
February 23, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28229819/dabigatran-aggravates-topoisomerase-i-peptide-loaded-dendritic-cells-induced-lung-and-skin-fibrosis
#3
Heena Mehta, Philippe-Olivier Goulet, Jade Desjardins, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
OBJECTIVES: Dysregulated coagulation cascade has been implicated in development of fibrosis in systemic sclerosis (SSc). Thrombin, a key mediator of the coagulation pathway, has both proinflammatory and procoagulant properties. Here, we evaluated the efficacy of oral dabigatran, a direct thrombin inhibitor, on topoisomerase I dendritic cells (TOPOIA DCs)-induced lung and skin fibrosis, an experimental model of SSc. METHODS: Mice were repeatedly immunized with TOPOIA DCs...
February 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28229423/patient-derived-and-intraoperatively-formed-biomaterial-for-tissue-engineering
#4
Shalmli U Joshi, Rares O Barbu, Melissa Carr-Reynolds, Brian Barnes, Syam P Nukavarapu
In this chapter, we introduce a completely intraoperative procedure for obtaining a patient-derived biomaterial in cell therapy and tissue engineering applications. An automated device for processing human peripheral-blood ensures a reproducible method for retrieving the patient's cellular-rich as well as cellular-poor plasma. By substituting calcium for animal-derived thrombin, we engineer a completely autologous hydrogel that eliminates the risk of disease transmission and lowers FDA regulation hurdles. Through this chapter, we will discuss a bedside protocol developed to prepare a patient-derived hydrogel...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28229167/mutation-in-a-highly-conserved-glycine-residue-in-strand-5b-of-plasminogen-activator-inhibitor-1-causes-polymerisation
#5
Takayuki Iwaki, Kotomi Nagahashi, Katsuhiro Takano, Katsue Suzuki-Inoue, Naohiro Kanayama, Kazuo Umemura, Tetsumei Urano
Serpinopathy is characterised as abnormal accumulation of serine protease inhibitors (SERPINs) in cells and results in clinical symptoms owing to lack of SERPIN function or excessive accumulation of abnormal SERPIN. We recently identified a patient with functional deficiency of plasminogen activator inhibitor-1 (PAI-1), a member of the SERPIN superfamily. The patient exhibited life-threatening bleeding tendencies, which have also been observed in patients with a complete deficiency in PAI-1. Sequence analysis revealed a homozygous single-nucleotide substitution from guanine to cytosine at exon 9, which changed amino acid residue 397 from glycine to arginine (c...
February 23, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28229158/detection-of-procoagulant-imbalance-modified-endogenous-thrombin-potential-with-results-expressed-as-ratio-of-values-with-to-without-thrombomodulin
#6
Armando Tripodi
Each individual possesses his/her own endogenous-thrombin-potential (ETP) (i. e. the ability to generate thrombin) which depends on the relative strength of the pro- and anticoagulant drivers operating in plasma. This ability depends in turn on the clinical conditions in which the balance between the two drivers is variably affected. One of the major determinants of this balance is the factor (F)VIII-protein C(PC) axis and its effect can be conveniently explored by the thrombin generation procedures with results expressed as ETP ratio with/without thrombomodulin (TM) (ETP-TM ratio)...
February 23, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28226413/thrombalexin-use-of-a-cytotopic-anticoagulant-to-reduce-thrombotic-microangiopathy-in-a-highly-sensitized-model-of-kidney-transplantation
#7
Miriam Manook, Jean Kwun, Christian Burghuber, Kannan Samy, Michael Mulvihill, Janghoon Yoon, He Xu, Andrea L MacDonald, Kyle Freischlag, Verna Curfman, Evelyn Branum, David Howell, Alton Brad Farris, Richard A Smith, Stephen Sacks, Anthony Dorling, Nizam Mamode, Stuart Knechtle
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anti-coagulation is difficult due to bleeding. A novel 'cytotopic' agent, 'Thrombalexin', (TLN) combines a cell-membrane bound (mirystoyl tail) anti-thrombin (HLL peptide) which can be perfused directly to the donor organ or cells.. Thromboelastography (TEG) was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN vs...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28225526/nonhuman-primate-model-of-polytraumatic-hemorrhagic-shock-recapitulates-early-platelet-dysfunction-observed-following-severe-injury-in-humans
#8
Leasha J Schaub, Hunter B Moore, Andrew P Cap, Jacob J Glaser, Ernest E Moore, Forest R Sheppard
BACKGROUND: Platelet dysfunction has been described as an early component of trauma-induced coagulopathy. The platelet component of trauma-induced coagulopathy remains to be fully elucidated and translatable animal models are required to facilitate mechanistic investigations. We sought to determine if the early platelet dysfunction described in trauma patients could be recapitulated in a nonhuman primate model of polytraumatic hemorrhagic shock. METHODS: Twenty-four male rhesus macaques weighting 7 to 14 kg were subjected to 60 minutes (min) of severe pressure-targeted controlled hemorrhagic shock (HS) with and without other injuries...
March 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28225026/blood-based-omic-profiling-supports-female-susceptibility-to-tobacco-smoke-induced-cardiovascular-diseases
#9
Aristotelis Chatziioannou, Panagiotis Georgiadis, Dennie G Hebels, Irene Liampa, Ioannis Valavanis, Ingvar A Bergdahl, Anders Johansson, Domenico Palli, Marc Chadeau-Hyam, Alexandros P Siskos, Hector Keun, Maria Botsivali, Theo M C M de Kok, Almudena Espín Pérez, Jos C S Kleinjans, Paolo Vineis, Soterios A Kyrtopoulos
We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223937/orthostatic-challenge-shifts-the-hemostatic-system-of-patients-recovered-from-stroke-toward-hypercoagulability
#10
Gerhard Cvirn, Markus Kneihsl, Christine Rossmann, Margret Paar, Thomas Gattringer, Axel Schlagenhauf, Bettina Leschnik, Martin Koestenberger, Erwin Tafeit, Gilbert Reibnegger, Irhad Trozic, Andreas Rössler, Franz Fazekas, Nandu Goswami
Aims: The objective of our study was to assess the effects of orthostatic challenge on the coagulation system in patients with a history of thromboembolic events and to assess how they compared with age-matched healthy controls. Methods: Twenty-two patients with histories of ischemic stroke and 22 healthy age-matched controls performed a sit-to-stand test. Blood was collected prior to- and at the end of- standing in the upright position for 6 min. Hemostatic profiling was performed by determining thrombelastometry and calibrated automated thrombogram values, indices of thrombin generation, standard coagulation times, markers of endothelial activation, plasma levels of coagulation factors and copeptin, and hematocrit...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28223242/fviia-prevents-the-progressive-hemorrhaging-of-a-brain-contusion-by-protecting-microvessels-via-formation-of-the-tf-fviia-fxa-complex
#11
Qiang Yuan, Dalong Zhang, Sirong Wu, Jian Yu, Lei Yu, Yirui Sun, Zhuoying Du, Zhiqi Li, Liangfu Zhou, Xing Wu, Jin Hu
Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions...
February 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28223215/bufadienolides-from-kalanchoe-daigremontiana-as-thrombin-inhibitors-in-vitro-and-in-silico-study
#12
Joanna Kolodziejczyk-Czepas, Malgorzata Sieradzka, Barbara Moniuszko-Szajwaj, Łukasz Pecio, Michal B Ponczek, Pawel Nowak, Anna Stochmal
Thrombin is an active plasma coagulation factor II, critical for the formation of fibrin clot during blood coagulation. For that reason, this protein is also a crucial target for different anti-thrombotic therapies. The work is based on in vitro evaluation of the inhibitory effect of bufadienolide-rich fraction, isolated from roots of Kalanchoe daigremontiana (1-50μg/ml) on enzymatic properties of a serine proteinase - thrombin. The efficacy of the inhibition of amidolytic activity of thrombin (measured as a hydrolysis of the chromogenic substrate S-2238, Chromogenix) attained about 10 and 66%, respectively...
February 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28220880/parenteral-administration-of-factor-xa-iia-inhibitors-limits-experimental-aortic-aneurysm-and-atherosclerosis
#13
Corey S Moran, Sai-Wang Seto, Smriti M Krishna, Surabhi Sharma, Roby J Jose, Erik Biros, Yutang Wang, Susan K Morton, Jonathan Golledge
Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE(-/-)) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE(-/-) mice...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220264/treatment-of-stage-ii-medication-related-osteonecrosis-of-the-jaw-with-necrosectomy-and-autologous-bone-marrow-mesenchymal-stem-cells
#14
Pit Jacob Voss, Akihiko Matsumoto, Esteban Alvarado, Rainer Schmelzeisen, Fabian Duttenhöfer, Philipp Poxleitner
Treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) remain controversial. Although the AAOMS suggests a conservative approach, a surgical management with necrosectomy is often required when conservative management has failed. Moreover, recent studies have shown promising results using an early stage surgical treatment. Over the past decade, cell-based bone regeneration utilizing bone marrow mesenchymal stem cells (MSCs) received increased attention. MSCs are known to promote wound healing and induce new bone formation in compromised tissue...
February 20, 2017: Odontology
https://www.readbyqxmd.com/read/28220154/dna-display-of-folded-rna-libraries-enabling-rna-selex-without-reverse-transcription
#15
I S MacPherson, J S Temme, I J Krauss
A method for the physical attachment of folded RNA libraries to their encoding DNA is presented as a way to circumvent the reverse transcription step during systematic evolution of RNA ligands by exponential enrichment (RNA-SELEX). A DNA library is modified with one isodC base to stall T7 polymerase and a 5' "capture strand" which anneals to the nascent RNA transcript. This method is validated in a selection of RNA aptamers against human α-thrombin with dissociation constants in the low nanomolar range. This method will be useful in the discovery of RNA aptamers and ribozymes containing base modifications that make them resistant to accurate reverse transcription...
February 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28219843/the-impact-of-the-endothelial-protein-c-receptor-on-thrombin-generation-and-clot-lysis
#16
Laura Pepler, Chengliang Wu, Dhruva J Dwivedi, Cynthia Wu, Paul Y Kim, Patricia C Liaw
INTRODUCTION: When thrombin is bound to thrombomodulin (TM), it becomes a potent activator of protein C (PC) and thrombin-activable fibrinolysis inhibitor (TAFI). Activation of PC is enhanced when PC is bound to the endothelial protein C receptor (EPCR). Activated protein C (APC) inhibits thrombin generation while activated TAFI (TAFIa) attenuates fibrinolysis. To determine the impact of diminished EPCR function on thrombin generation and fibrinolysis we generated cells that expressed TM and a variant of EPCR (R96C) that does not bind PC...
February 3, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28219621/topical-application-of-recombinant-activated-factor-vii-during-cesarean-section-for-placenta-previa
#17
Birgit Tbg Schjoldager, Emmeli Mikkelsen, Malene R Lykke, Jørgen Præst, Anne-Mette Hvas, Lars Heslet, Niels J Secher, Jannie D Salvig, Niels Uldbjerg
BACKGROUND: During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principal of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII (FVIIa). OBJECTIVE: We hypothesized that topical application of recombinant FVIIa (rFVIIa) at the placenta site reduces the bleeding without affecting the intravascular coagulation...
February 17, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28218264/hypertension-thrombin-amplification-loop-in-hypertension
#18
Susan J Allison
No abstract text is available yet for this article.
February 20, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28218251/stim1-phosphorylation-at-y361-recruits-orai1-to-stim1-puncta-and-induces-ca-2-entry
#19
Pascal Yazbeck, Mohammad Tauseef, Kevin Kruse, Md-Ruhul Amin, Rayees Sheikh, Stefan Feske, Yulia Komarova, Dolly Mehta
Store-operated Ca(2+) entry (SOCE) mediates the increase in intracellular calcium (Ca(2+)) in endothelial cells (ECs) that regulates several EC functions including tissue-fluid homeostasis. Stromal-interaction molecule 1 (STIM1), upon sensing the depletion of (Ca(2+)) from the endoplasmic reticulum (ER) store, organizes as puncta that trigger store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+)-selective Orai1 channels. While the STIM1 and Orai1 binding interfaces have been mapped, signaling mechanisms activating STIM1 recruitment of Orai1 and STIM1-Orai1 interaction remains enigmatic...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28214869/effects-of-antimalarial-tafenoquine-on-blood-platelet-activity-and-survival
#20
Hang Cao, Rosi Bissinger, Anja T Umbach, Abdulla Al Mamun Bhuyan, Florian Lang, Meinrad Gawaz
BACKGROUND/AIMS: The 8-aminoquinoline tafenoquine has been shown to be effective against Plasmodia, Leishmania and Trypanosoma. The substance is at least in part effective by triggering apoptosis of the parasites. Moreover, tafenoquine has been shown to trigger eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. The effect of tafenoquine on eryptosis is in part due to stimulation of Ca2+ entry and oxidative stress...
January 26, 2017: Cellular Physiology and Biochemistry
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