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https://www.readbyqxmd.com/read/28925023/fibrinolysis-from-blood-to-the-brain
#1
Robert L Medcalf
We all know about classical fibrinolysis, how plasminogen activation by either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) promotes fibrin breakdown, and how this process was harnessed for the therapeutic removal of blood clots. While this is still perfectly true and still applicable to thromboembolic conditions today, another dimension to this system came to light over two decades ago that implicated the plasminogen activating system in a context far removed from the dissolution of blood clots...
September 19, 2017: Journal of Thrombosis and Haemostasis: JTH
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
#2
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/28916826/in-vitro-and-in-vivo-biocompatibility-evaluation-of-polyallylamine-and-macromolecular-heparin-conjugates-modified-alginate-microbeads
#3
Vijayaganapathy Vaithilingam, Bjørg Steinkjer, Liv Ryan, Rolf Larsson, Bernard Edward Tuch, Jose Oberholzer, Anne Mari Rokstad
Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC)...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915711/vitamin-k-and-its-analogs-potential-avenues-for-prostate-cancer-management
#4
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
#5
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/28903884/successful-outcome-of-severe-intra-cerebral-bleeding-associated-with-acquired-factor-v-inhibition-utilization-of-multiple-therapeutic-agents
#6
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/28844963/novel-direct-factor-xa-inhibitory-compounds-from-tenebrio-molitor-with-anti-platelet-aggregation-activity
#7
Wonhwa Lee, Mi-Ae Kim, InWha Park, Jae Sam Hwang, MinKyun Na, Jong-Sup Bae
Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo(L-Pro-L-Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619...
August 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28843665/balanced-haemostasis-with-both-hypo-and-hyper-coagulable-features-in-critically-ill-patients-with-acute-on-chronic-liver-failure
#8
Caleb Fisher, Vishal C Patel, Sidsel Hyldgaard Stoy, Arjuna Singanayagam, Jelle Adelmeijer, Julia Wendon, Debbie L Shawcross, Ton Lisman, William Bernal
BACKGROUND: Cirrhotic patients have complex haemostatic abnormalities. Current evidence suggests stable cirrhotic (SC) patients have a "re-balanced" haemostatic state. However, limited data exists in acute decompensated (AD) or acute on chronic liver failure (ACLF) patients. METHODS: We utilised thrombin generation analysis, fibrinolysis assessment, and evaluation of haemostatic parameters to assess haemostasis in liver disease of progressive severity. RESULTS: The study cohorts were comprised of: SC, n=8; AD n=44; ACLF, n=17; and Healthy Control (HC), n=35...
August 17, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28837614/mice-deficient-in-the-anti-haemophilic-coagulation-factor-viii-show-increased-von-willebrand-factor-plasma-levels
#9
Klytaimnistra Kiouptsi, Alexandra Grill, Amrit Mann, Mareike Döhrmann, Maren Lillich, Sven Jäckel, Frano Malinarich, Henning Formes, Davit Manukyan, Saravanan Subramaniam, Avinash Khandagale, Cornelia Karwot, Serge C Thal, Markus Bosmann, Inge Scharrer, Kerstin Jurk, Christoph Reinhardt
Von Willebrand factor (VWF) is the carrier protein of the anti-haemophilic Factor VIII (FVIII) in plasma. It has been reported that the infusion of FVIII concentrate in haemophilia A patients results in lowered VWF plasma levels. However, the impact of F8-deficiency on VWF plasma levels in F8-/y mice is unresolved. In order to avoid confounding variables, we back-crossed F8-deficient mice onto a pure C57BL/6J background and analysed VWF plasma concentrations relative to C57BL/6J WT (F8+/y) littermate controls...
2017: PloS One
https://www.readbyqxmd.com/read/28834179/human-pancreatic-tumors-grown-in-mice-release-tissue-factor-positive-microvesicles-that-increase-venous-clot-size
#10
Y Hisada, C Ay, A C Auriemma, B C Cooley, N Mackman
BACKGROUND: Pancreatic cancer patients have a high rate of venous thromboembolism. Human pancreatic tumors and cell lines express high levels of tissue factor (TF) and release TF-positive microvesicles (TF+MVs). In pancreatic cancer patients, tumor-derived TF+MVs are present in blood and increased levels are associated with venous thromboembolism and decreased survival. Previous studies have shown that mice with orthotopic human or murine pancreatic tumors have circulating tumor-derived TF+MVs, an activated clotting system, and larger clots than controls in an inferior vena cava stenosis model...
August 22, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28828982/development-of-benzimidazole-derivatives-as-novel-anti-platelet-drugs
#11
Wei-Cheng Yao, Lan-Ting Yuan, Wen-Bin Yang, Chih-Hsuan Hsia, Li-Ting Huang, Tzu-Yin Lee, Joen-Rong Sheu, Wan-Jung Lu, Thanasekaran Jayakumar, Ray-Jade Chen
BACKGROUND: Benzimidazoles are privileged biomolecules which form an integral part of vitamin B12 and have been attracting numerous researchers all over the world to assess their potential therapeutic significance. OBJECTIVES: The comparative in vitro antiplatelet activity of newly synthesized benzimidazole derivatives, M3BIM, C2BIM, and L2BIM in thrombin, adenosine diphosphate (ADP) and epinephrine-induced washed human platelets was investigated. METHODS: Reversed-phase silica gel column chromatography, Aggregometry, Flow cytometry and Immunoblotting were used in this study...
August 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28820035/changes-in-heparin-dose-response-slope-during-cardiac-surgery-possible-result-in-inaccuracy-in-predicting-heparin-bolus-dose-requirement-to-achieve-target-act
#12
Junko Ichikawa, Tetsu Mori, Mitsuharu Kodaka, Keiko Nishiyama, Makoto Ozaki, Makiko Komori
INTRODUCTION: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. METHODS: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system...
September 2017: Perfusion
https://www.readbyqxmd.com/read/28819975/compatibility-of-nitric-oxide-release-with-implantable-enzymatic-glucose-sensors-based-on-osmium-iii-ii-mediated-electrochemistry
#13
Kyoung Ha Cha, Mark E Meyerhoff
The compatibility of nitric oxide (NO) release coatings with implantable enzymatic glucose sensors based on osmium (III/II) mediated electrochemical detection is examined for the first time. NO-releasing osmium-mediated glucose sensors are prepared using a S-nitrosothiol impregnated outer tubing and are tested in vitro in both phosphate buffer (pH 7.4) and whole porcine blood. It is demonstrated that after 3 days of continuous NO release at or above physiological levels, there are no negative effects on the osmium mediated electrochemical currents...
August 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28816059/atherothrombosis-and-oxidative-stress-mechanisms-and-management-in-elderly
#14
Francesco Violi, Lorenzo Loffredo, Roberto Carnevale, Pasquale Pignatelli, Daniele Pastori
SIGNIFICANCE The incidence of cardiovascular events increases by aging, representing the main cause of death in old population. Aging is associated with over-production of reactive oxygen species (ROS), which may affect clotting and platelet activation, and impair endothelial function so predisposing elderly patients to thrombotic complications. RECENT ADVANCES There are increasing evidences to suggest that aging is associated with an imbalance between oxidative stress and antioxidant status. Thus, up-regulation of ROS-producing enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, along with down-regulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occur during aging...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28804832/measuring-direct-oral-anticoagulants
#15
Robert C Gosselin, Jonathan Douxfils
Direct oral anticoagulants (DOACs) can be quantified using methods that can be performed in any clinical or research laboratory using manual or automated instrument platforms. Dabigatran etexilate, the oral direct thrombin inhibitor, can be quantified by drug-calibrated clot or chromogenic-based assays using either thrombin or ecarin as substrates. Oral direct anti-Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban, can be quantified with drug-calibrated anti-Xa kits or reagents as typically used for measuring heparins (unfractionated, low molecular weight, or pentasaccharides)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28803708/anti-phospholipid-syndrome-current-opinion-on-mechanisms-involved-laboratory-characterization-and-diagnostic-aspects
#16
REVIEW
Jean Amiral, Marie Peyrafitte, Claire Dunois, Anne Marie Vissac, Jerard Seghatchian
Anti-phospholipid syndrome is a complex and severe clinical situation, associated with symptoms such as recurrent thrombosis, arterial or venous, at any site, pregnancy loss, and other related syndromes. These clinical burdens, are highly variable from patient to patient, and are associated with biological abnormalities, such as the presence of the Lupus Anticoagulant or phospholipid dependent antibodies, confirmed on two occasions at least 12 weeks apart. From the diagnosis standpoint, both, functional (clotting) or immunological assays, are difficult to standardize and to optimize, due to the absence of reference material, or a characteristic clinical group, and international reference preparations...
July 15, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28777290/anti-coagulant-and-anti-thrombotic-properties-of-blacklip-abalone-haliotis-rubra-in-vitro-and-animal-studies
#17
Hafiz Ansar Rasul Suleria, Paul P Masci, Kong-Nan Zhao, Rama Addepalli, Wei Chen, Simone A Osborne, Glenda C Gobe
Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation)...
August 4, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28755727/plasma-antiphospholipid-antibodies-effects-on-activated-partial-thromboplastin-time-assays
#18
Ke Yao, Lingyun Zhang, Hang Zhou, Ning Tang, Dengju Li
BACKGROUND: Activated partial thromboplastin time (aPTT) assays can be affected by plasma antiphospholipid antibodies (aPLs), but the degree of the interference is not easy to predict. This study aimed to investigate the effects on aPTT assay results of different types and combinations of aPLs, including anti-β2-glycoprotein I antibodies, anticardiolipin antibodies and lupus anticoagulant. MATERIALS AND METHODS: We retrospectively collected clinical information and laboratory tests from aPL-positive patients...
July 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28748111/dimerized-domain-v-of-beta2-glycoprotein-i-is-sufficient-to-upregulate-procoagulant-activity-in-pma-treated-u937-monocytes-and-require-intact-residues-in-two-phospholipid-binding-loops
#19
Alexey Kolyada, David A Barrios, Natalia Beglova
Upregulation of the procoagulant activity of monocytes by antibodies to beta2- glycoprotein I (β2GPI) is one of the mechanisms contributing to thrombosis in antiphospholipid syndrome. Current knowledge about receptors responsible for the upregulation of procoagulant activity by β2GPI/anti-β2GPI complexes and their binding sites on β2GPI is far from complete. We quantified the procoagulant activity expressed by phorbol 12-myristate 13-acetate (PMA)- differentiated U937 cells by measuring clotting kinetics in human plasma exposed to stimulated cells...
June 2017: Antibodies
https://www.readbyqxmd.com/read/28718695/enhanced-procoagulant-activity-of-platelets-after-chemotherapy-in-non-small-cell-lung-cancer
#20
Ruishuang Ma, Yayan Bi, Junjie Kou, Jin Zhou, Jialan Shi
The procoagulant status of patients with non-small cell lung cancer (NSCLC) after chemotherapy is poorly characterized and the role of platelets in hypercoagulative state of NSCLC is unknown. The aim of this study was to evaluate the procoagulant activity (PCA) of platelets in NSCLC before and after chemotherapy. The subjects were 52 patients newly diagnosed with NSCLC. The patients had decreased clotting time compared with healthy subjects, and the thrombin-antithrombin complex increased 2.5 fold after chemotherapy...
July 18, 2017: Cancer Biology & Therapy
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