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Clotting factors

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https://www.readbyqxmd.com/read/28935443/complex-formation-with-protamine-prolongs-the-thrombin-inhibiting-effect-of-dna-aptamer-in-vivo
#1
V A Spiridonova, T M Novikova, D M Nikulina, T A Shishkina, E V Golubkina, O S Dyukareva, N N Trizno
Antithrombin DNA aptamersRE31 are single-chain oligonucleotides that fold into three-dimensional forms allowing them to bind the enzyme with high affinity and inhibit its activity in vivo. They are rapidly degraded by a nonspecific nuclease, and, to prolong the lifetime of the aptamer DNA in the bloodstream, it is necessary to coat it with a polymer envelope. A new approach to solving this problem based on preparation of DNA-polyelectrolyte complexes with a minimal particle size that can circulate with blood flow...
September 18, 2017: Biochimie
https://www.readbyqxmd.com/read/28935233/substrate-delivery-mechanism-and-the-role-of-membrane-curvature-in-factor-x-activation-by-extrinsic-tenase
#2
Tatiana A Kovalenko, Mikhail A Panteleev, Anastasia N Sveshnikova
Membrane-bound enzyme complex of extrinsic tenase (VIIa/TF) is believed to be the primary activator of blood clotting in vivo. This complex (where factor VIIa (FVIIa) is a catalytically active part and tissue factor (TF) is its essential cofactor) activates its primary substrate factor X (FX) leading to factor Xa (FXa) ('a' stands for 'activated'). Both FX and FXa are able to bind to phospholipid membrane and, therefore, are distributed between solution and membrane surface. As a result, two possible mechanisms of substrate delivery to the extrinsic tenase exist: via lateral diffusion on the membrane surface or directly from the solution...
September 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28934884/effect-of-a-rapidly-degrading-presolidified-10-kda-chitosan-blood-implant-and-subchondral-marrow-stimulation-surgical-approach-on-cartilage-resurfacing-in-a-sheep-model
#3
Angela D Bell, Mark B Hurtig, Eric Quenneville, Georges-Étienne Rivard, Caroline D Hoemann
Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole...
October 2017: Cartilage
https://www.readbyqxmd.com/read/28932824/factor-viia-interaction-with-epcr-modulates-the-hemostatic-effect-of-rfviia-in-hemophilia-therapy-mode-of-its-action
#4
Shiva Keshava, Jagan Sundaram, Anuradha Rajulapati, Charles Esmon, Usha Pendurthi, L Vijaya Mohan Rao
Recent studies established that clotting factor VIIa (FVIIa) binds endothelial cell protein C receptor (EPCR). It has been speculated that FVIIa interaction with EPCR might augment the hemostatic effect of rFVIIa in therapeutic conditions. The present study is carried out to investigate the mechanism by which FVIIa interaction with EPCR contributes to the hemostatic effect of rFVIIa in hemophilia therapy. Active-site inhibited FVIIa, which is capable of binding to EPCR but has no ability to activate factor X, reduced the concentration of rFVIIa required to correct the bleeding following the saphenous vein injury in mouse hemophilia model systems...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#5
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28924251/cyanobacterial-exopolymer-properties-differentiate-microbial-carbonate-fabrics
#6
Fumito Shiraishi, Yusaku Hanzawa, Tomoyo Okumura, Naotaka Tomioka, Yu Kodama, Hiroki Suga, Yoshio Takahashi, Akihiro Kano
Although environmental changes and evolution of life are potentially recorded via microbial carbonates, including laminated stromatolites and clotted thrombolites, factors controlling their fabric are still a matter of controversy. Herein, we report that the exopolymer properties of different cyanobacterial taxa primarily control the microbial carbonates fabrics in modern examples. This study shows that the calcite encrustation of filamentous Phormidium sp. secreting acidic exopolymers forms the laminated fabric of stromatolites, whereas the encrustation of coccoid Coelosphaeriopsis sp...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922951/a-retrospective-study-of-cytokine-profiles-changes-in-mice-with-fviii-inhibitor-development-after-aav-mediated-gene-therapy-in-hemophilia-a-mouse-model
#7
Junjiang Sun, Zhenhua Yuan, Yasmina L Abajas, Dorreen E Szollosi, Genlin Hu, Baolai Hua, Xiao Xiao, Chengwen Li
The development of inhibitory autoantibodies to the infused clotting factor VIII is a major complication for severe hemophilia A management. Novel therapy options for hemophilia have significantly progressed in the last decade and a gene therapy cure for hemophilia is translating into reality. However, mechanistic studies of FVIII autoantibodies (FVIII inhibitors) have lagged behind and remain a challenge for both protein replacement and gene therapy. FVIII inhibitor formation is assumed to be a classical T cell-dependent immune response in which cytokines/chemokines play an important role...
September 19, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28920906/clotchip-a-microfluidic-dielectric-sensor-for-point-of-care-assessment-of-hemostasis
#8
Debnath Maji, Michael A Suster, Erdem Kucukal, Ujjal D S Sekhon, Anirban Sen Gupta, Umut A Gurkan, Evi X Stavrou, Pedram Mohseni
This paper describes the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy of human whole blood during coagulation. The sensor, termed ClotChip, employs a three-dimensional, parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Interfaced with an impedance analyzer, the ClotChip measures the complex relative dielectric permittivity, ϵ Tr, of human whole blood in the frequency range of 40 Hz to 100 MHz. The temporal variation in the real part of the blood dielectric permittivity at 1 MHz features a time to reach a permittivity peak, Tpeak, as well as a maximum change in permittivity after the peak, ∆εr,max, as two distinct parameters of ClotChip readout...
September 12, 2017: IEEE Transactions on Biomedical Circuits and Systems
https://www.readbyqxmd.com/read/28918098/identifying-novel-factor-xiia-inhibitors-with-pca-ga-svm-developed-vhts-models
#9
Jonathan Jun Feng Chen, Donald P Visco
There currently is renewed interest in blood clotting Factor XII as a potential target for thrombosis inhibition. Historically untargeted, there is little drug information with which to start drug candidate searches. Typical high-throughput screening can identify potential drug candidates, but is inefficient. Virtual high-throughput screening can be used to raise efficiency by focusing experimental efforts on compounds predicted to be active and is applied here to identify new Factor XIIa inhibitors. We combine principal component analysis, genetic algorithm and support vector machine to create the models used in the virtual high-throughput screening...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28917273/mechanisms-and-risk-factors-of-thrombosis-in-cancer
#10
REVIEW
Anna Falanga, Laura Russo, Viola Milesi, Alfonso Vignoli
The close relationship between cancer and thrombosis is known since more than a century. Venous thromboembolism (VTE) may be the first manifestation of an occult malignancy in an otherwise healthy individual. Cancer patients commonly present with abnormalities of laboratory coagulation tests, indicating an ongoing subclinical hypercoagulable condition. The results of laboratory tests demonstrate that a process of fibrin formation and removal parallels the development of malignancy, which is of particular interest since fibrin and other clotting products are important for both thrombogenesis and tumor progression...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28915711/vitamin-k-and-its-analogs-potential-avenues-for-prostate-cancer-management
#11
REVIEW
Subramanyam Dasari, Syed M Ali, Guoxing Zheng, Aoshuang Chen, Venkata Satish Dontaraju, Maarten C Bosland, Andre Kajdacsy-Balla, Gnanasekar Munirathinam
Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914800/effect-of-clotting-duration-and-temperature-on-bdnf-measurement-in-human-serum
#12
Patrizia Amadio, Leonardo Sandrini, Alessandro Ieraci, Elena Tremoli, Silvia Stella Barbieri
Brain-derived neurothrophic factor (BDNF) is a neurotrophin expressed in different tissues and cells, including neurons, endothelial cells, leukocytes, megakaryocytes and platelets. Modifications of BDNF in plasma and/or in serum are associated with neurodegenerative and psychiatric disorders, cardiovascular diseases, metabolic syndrome and with mortality risk. Indeed, changes in blood levels of BDNF may reflect those of its tissue of origin and/or promote pathological dysfunctions. The measurement of BDNF amount in plasma or in serum has been characterized with particular attention in the impact of different anti-coagulants, clotting duration, temperature (≤21 °C) and delay in blood sample centrifugation as well as in stability of storage...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28913590/challenges-of-anticoagulation-therapy-in-pregnancy
#13
REVIEW
Annemarie E Fogerty
Thrombotic complications in pregnancy represent a major cause of morbidity and mortality. Pregnancy is a primary hypercoagulable state due to enhanced production of clotting factors, a decrease in protein S activity, and inhibition of fibrinolysis. These physiologic changes will yield a collective rate of venous thromboembolism (VTE) of about 1-2 in 1000 pregnancies for the general obstetric population, which represents a five- to tenfold increased risk in pregnancy compared to age-matched non-pregnant peers...
September 14, 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28912777/class-a-cpg-oligonucleotide-priming-rescues-mice-from-septic-shock-via-activation-of-platelet-activating-factor-acetylhydrolase
#14
Yoshinari Yamamoto, Ryu Sugimura, Takafumi Watanabe, Suguru Shigemori, Takuma Okajima, Shireen Nigar, Fu Namai, Takashi Sato, Tasuku Ogita, Takeshi Shimosato
Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF) induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585) strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28905885/long-term-correction-of-hemophilia-a-mice-following-lentiviral-mediated-delivery-of-an-optimized-canine-factor-viii-gene
#15
J M Staber, M J Pollpeter, C-G Anderson, M Burrascano, A L Cooney, P L Sinn, D T Rutkowski, W C Raschke, P B McCray
Current therapies for hemophilia A include frequent prophylactic or on-demand intravenous factor treatments which are costly, inconvenient and may lead to inhibitor formation. Viral vector delivery of factor VIII (FVIII) cDNA has the potential to alleviate the debilitating clotting defects. Lentiviral-based vectors delivered to murine models of hemophilia A mediate phenotypic correction. However, a limitation of lentiviral-mediated FVIII delivery is inefficient transduction of target cells. Here, we engineer a feline immunodeficiency virus (FIV) -based lentiviral vector pseudotyped with the baculovirus GP64 envelope glycoprotein to mediate efficient gene transfer to mouse hepatocytes...
September 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28904799/clinical-significance-of-measuring-plasminogen-activator-inhibitor-1-in-sepsis
#16
Toshiaki Iba, Jecko Thachil
BACKGROUND: Disseminated thrombotic process in the microcirculation is considered to be an important cause of multiple organ dysfunction in sepsis. The fundamental purpose of this prothrombotic change was believed to be in the host defense against microbial dissemination. In that process, antifibrinolytic property plays an important role. MAIN BODY: For the understanding of pathophysiology of sepsis, it is quite useful to grasp the alterations in coagulation/fibrinolytic parameters, i...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28904675/von-willebrand-s-disease-case-report-and-review-of-literature
#17
REVIEW
Hanae Echahdi, Brahim El Hasbaoui, Mohamed El Khorassani, Aomar Agadr, Mohamed Khattab
Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL)...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28904343/engineered-factor-xa-variants-retain-procoagulant-activity-independent-of-direct-factor-xa-inhibitors
#18
Daniël Verhoef, Koen M Visscher, C Ruben Vosmeer, Ka Lei Cheung, Pieter H Reitsma, Daan P Geerke, Mettine H A Bos
The absence of an adequate reversal strategy to prevent and stop potential life-threatening bleeding complications is a major drawback to the clinical use of the direct oral inhibitors of blood coagulation factor Xa. Here we show that specific modifications of the substrate-binding aromatic S4 subpocket within the factor Xa active site disrupt high-affinity engagement of the direct factor Xa inhibitors. These modifications either entail amino-acid substitution of S4 subsite residues Tyr99 and/or Phe174 (chymotrypsinogen numbering), or extension of the 99-loop that borders the S4 subsite...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28903884/successful-outcome-of-severe-intra-cerebral-bleeding-associated-with-acquired-factor-v-inhibition-utilization-of-multiple-therapeutic-agents
#19
Panagiotis Andreadis, Katerina Kafantari, Aleka Agapidou, Sofia Vakalopoulou, Efthymia Vlachaki
BACKGROUND: Acquired coagulation Factor inhibitors are antibodies that either inhibit the activity or increase the clearance of a clotting factor leading to an increased risk of bleeding. Most of the times, the disorder is attributed to Factor VIII inhibition (Acquired Hemophilia A), however other coagulation factors could also be implicated. CASE REPORT: We herein would like to report an interesting case of a patient who underwent Coronary Artery Bypass Graft and received antibiotic treatment after surgery with a third-generation cephalosporin...
September 13, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28900369/the-local-clinical-validation-of-a-new-lithium-heparin-tube-with-a-barrier-bd-vacutainer%C3%A2-barricor-lh-plasma-tube
#20
Fatma Demet Arslan, Inanc Karakoyun, Banu Isbilen Basok, Merve Zeytinli Aksit, Anil Baysoy, Yasemin Kilic Ozturk, Yusuf Adnan Guclu, Can Duman
INTRODUCTION: Although serum-providing blood tubes with a barrier are still widely used due to their significant advantages, the use of blood tubes with a barrier to provide plasma is becoming widespread. We compared 22 analytes in a BD Vacutainer® Barricor LH Plasma tube for local clinical validation of this new lithium heparin tube with a barrier. MATERIALS AND METHODS: Samples from 44 volunteers were collected in different tubes (Becton Dickinson and Company): Z tube without additive (reference), clot-activator tube with gel (SST), lithium heparin tube without gel (LiH), and lithium heparin tube with barrier (Barricor)...
October 15, 2017: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
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