المؤلفون: Christina Jern, Magnus Gisslén, Tara M. Stanne, Annie Pedersen

المصدر: Thrombosis Research
bioRxiv

مصطلحات موضوعية: medicine.medical_specialty, 2019-20 coronavirus outbreak, FVII, coagulation factor VII, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Hospitalized patients, medicine.medical_treatment, Letter to the Editors-in-Chief, vWF, von Willebrand factor, Disease, Article, t-PA, tissue-type plasminogen activator, Risk Factors, FIX, coagulation factor IX, Internal medicine, Fibrinolysis, medicine, Humans, TM, thrombomodulin, u-PA, urokinase-type plasminogen activator, DIC, disseminated intravascular coagulation, Risk factor, IL-6, interleukin-6, PAI-1, plasminogen activator inhibitor type 1, PAR-1, proteinase-activated receptor 1, TFPI, tissue factor pathway inhibitor, LDH, lactate dehydrogenase, SARS-CoV-2, business.industry, Anticoagulant, COVID-19, Hematology, APC, activated protein C, Hospitalization, TF, tissue factor, CRP, C-reactive protein, uPAR, urokinase-type plasminogen activator receptor, business, Protein C, medicine.drug

الوصف: COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins. By comparing patients who died to severely ill patients who survived, we identify dynamic immunomodulatory and tissue-associated proteins associated with survival, providing insights into which host responses are beneficial and which are detrimental to survival. We identify intracellular death signatures from specific tissues and cell types, and by associating these with angiotensin converting enzyme 2 (ACE2) expression, we map tissue damage associated with severe disease and propose which damage results from direct viral infection rather than from indirect effects of illness. We find that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells. Based on these results, we propose a model of immune and epithelial cell interactions that drive cell-type specific and tissue-specific damage in severe COVID-19.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71e3ec2a9b16c150f69513abb0ae2dd0Test
https://doi.org/10.1016/j.thromres.2021.05.016Test

المؤلفون: Janneke Horn, Maryse A. Wiewel, Tom van der Poll, Marcus J. Schultz, Karin C. A. A. Wildhagen, Roy Schrijver, Chris P. M. Reutelingsperger, Gerry A. F. Nicolaes

المساهمون: Graduate School, AII - Amsterdam institute for Infection and Immunity, Intensive Care Medicine, ANS - Amsterdam Neuroscience, Infectious diseases, Center of Experimental and Molecular Medicine, Promovendi CD, Biochemie, RS: CARIM - R1 - Thrombosis and haemostasis

المصدر: Thrombosis research, 136(3), 542-547. Elsevier Limited
Thrombosis Research, 136(3), 542-547. Elsevier Science

مصطلحات موضوعية: Male, medicine.medical_specialty, Thrombin generation, Antithrombin, Inflammation, Biology, Sensitivity and Specificity, Antithrombins, law.invention, Sepsis, Histones, chemistry.chemical_compound, law, Risk Factors, Internal medicine, Lactate dehydrogenase, medicine, Extracellular, Humans, Platelet, Mortality, Tissue homeostasis, Hydro-Lyases, Netherlands, Platelet Count, Incidence, Reproducibility of Results, NETosis, Hematology, Middle Aged, medicine.disease, Prognosis, Intensive care unit, Survival Rate, Endocrinology, chemistry, Immunology, Female, medicine.symptom, Biomarkers, medicine.drug

الوصف: Objective: Sepsis is a leading cause of death worldwide. Extracellular histones are cytotoxic compounds mediating death in murine sepsis and circulating nucleosome levels predict mortality in human inflammation and sepsis. Whether or not circulating extracellular histone H3 correlates with other plasma parameters and/or ICU scoring systems has not been completely established, nor if levels of circulating extracellular histones can be used as predictive markers for clinical outcome in sepsis. Methods: We measured plasma histone H3 (H3) levels in the plasma of 43 sepsis patients who were admitted to the Intensive Care Unit and determined their correlation with disease severity, organ failure, mortality and coagulation-and tissue homeostasis parameters including LDH levels, thrombin potential (ETP), prothrombin levels, antithrombin levels and platelet counts. Results: Median H3 levels of sepsis patients at the ICU were significantly increased in non-survivors as compared to survivors with levels found being 3.15 mu g/ml versus 0.57 mu g/ml respectively, P = 0.04. H3 levels are positively correlated with lactate dehydrogenase (LDH) activity (Spearman's rho = 0.49, P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6f38d944b46cacbae0691d1432d6f78Test
https://cris.maastrichtuniversity.nl/en/publications/183d6dc8-7668-4e10-bf40-bf83d8065d63Test

المؤلفون: Jin Ho Chung, Joo-Young Lee, Seung-Min Chung, Yeo-Pyo Yun, Ok-Nam Bae, Ga-Young Chung, Moo-Yeol Lee, Chang-Kiu Moon, Young Chul Kim

المصدر: Thrombosis Research. 111:179-183

مصطلحات موضوعية: Blood Platelets, Male, Serotonin, medicine.medical_specialty, Time Factors, Free Radicals, medicine.disease_cause, Streptozocin, Diabetes Mellitus, Experimental, Rats, Sprague-Dawley, chemistry.chemical_compound, Menadione, Lactate dehydrogenase, Internal medicine, medicine, Animals, Platelet, Cytotoxicity, L-Lactate Dehydrogenase, Chemically Induced Cytotoxicity, Vitamin K 3, Hematology, Glutathione, Streptozotocin, Antifibrinolytic Agents, Rats, Oxidative Stress, Endocrinology, chemistry, Reactive Oxygen Species, Oxidative stress, medicine.drug

الوصف: To study whether chemically induced cytotoxicity occurs in diabetic platelets, platelets isolated from rats made hyperglycemic (diabetic) by a prior intravenous administration of streptozotocin were incubated with menadione and the cytotoxicity was assessed by the amount of lactate dehydrogenase (LDH) released from the menadione exposed platelets as a function of time. Platelets isolated from diabetic rats released greater amount of LDH in response to menadione than those from normal rats. Consistent with this finding, induction of menadione cytotoxicity was not dependent on glutathione depletion, but on greater generation of free radicals in diabetic platelets. Greater sensitivity of diabetic platelets to the menadione-induced cytotoxicity was accompanied by release of serotonin from dense granules, suggesting that this mechanism contributes to cardiovascular diseases in diabetic subjects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::491800cc64b07a5c6d16686f87ebecfcTest
https://doi.org/10.1016/j.thromres.2003.09.003Test

المؤلفون: Jordan Kountchev, Johannes Mair, Angelika Hammerer-Lercher, Wolfgang Schobersberger, Josef Margreiter, Anton Klingler, Markus Mittermayr

المصدر: Thrombosis Research. 108:249-255

مصطلحات موضوعية: Male, medicine.medical_specialty, Time Factors, Ischemia, Blood Pressure, Enzyme-Linked Immunosorbent Assay, Myocardial Reperfusion Injury, Prostacyclin, 6-Ketoprostaglandin F1 alpha, In Vitro Techniques, Antithrombins, Ventricular Function, Left, Rats, Sprague-Dawley, Contractility, Coronary Circulation, Internal medicine, Troponin I, Animals, Medicine, cardiovascular diseases, Creatine Kinase, Dose-Response Relationship, Drug, L-Lactate Dehydrogenase, biology, business.industry, Myocardium, Antithrombin, Heart, Hematology, medicine.disease, Epoprostenol, Rats, carbohydrates (lipids), Endocrinology, Anesthesia, biology.protein, Creatine kinase, business, Reperfusion injury, Perfusion, circulatory and respiratory physiology, medicine.drug

الوصف: Introduction: Antithrombin (AT) is well known as an important inhibitor of the coagulation system. An interesting new hypothesis is that antithrombin exerts specific anti-inflammatory effects by stimulating the production of prostacyclin in endothelial cells. Recent studies report beneficial influence on ischemia/reperfusion injury in several organs. These effects are independent of the coagulation system. We investigated the influence of antithrombin on ischemia/reperfusion injury and prostacyclin release in the isolated rat heart. Since the perfusion of the hearts was without blood, the used model essentially describes effects of antithrombin on endothelial cells. Material and methods: Experiments were performed using the temperature-controlled and pressure-constant Langendorff apparatus. The hearts of 32 male Sprague–Dawley rats were subjected to 20 min of global ischemia followed by 30 min of reperfusion. Antithrombin was administered in three different concentrations (1, 4 and 8 U/ml) 15 min prior to global ischemia. Cardiac contractility parameters and biochemical parameters were measured. Results: Treatment with antithrombin did not increase the release of prostacyclin significantly after ischemia. Antithrombin at a concentration of 8 U/ml led to a significant increase in creatine kinase (CK; p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::38ced4cecce18b9a78ae67dc85547362Test
https://doi.org/10.1016/s0049-3848Test(03)00031-8

المؤلفون: Federico Mecacci, Lucia Carignani, Gianfranco Scarselli, Elena Parretti, Riccardo Cioni, Anna Piccioli, Marcella Mignosa, Giorgio Mello

المصدر: Thrombosis Research. 102:99-105

مصطلحات موضوعية: Adult, HELLP Syndrome, medicine.medical_specialty, Time Factors, HELLP syndrome, medicine.drug_class, Hematocrit, Dexamethasone, Statistics, Nonparametric, Preeclampsia, Pregnancy, medicine, Humans, Blood Transfusion, Retrospective Studies, Disseminated intravascular coagulation, L-Lactate Dehydrogenase, medicine.diagnostic_test, Heparin, Platelet Count, business.industry, Anticoagulant, Hematology, Microangiopathic hemolytic anemia, Disseminated Intravascular Coagulation, medicine.disease, Surgery, Hospitalization, Treatment Outcome, Anesthesia, Female, business, medicine.drug

الوصف: HELLP syndrome is a severe complication of pregnancy characterized by microangiopathic hemolytic anemia, hepatic dysfunction and thrombocytopenia. Though delivery is the ultimate therapeutic option, medical treatments, including the use of heparin or corticosteroids, have been employed in the attempt to improve maternal prognosis. The aim of this retrospective study was to compare the time course of recovery and the incidence of complications in women with HELLP syndrome receiving either heparin or dexamethasone. Between January 1990 and December 1998, 32 patients with HELLP syndrome were cared for at the Institute of Obstetrics and Gynecology of the University of Florence: 20 patients were treated with heparin, administered subcutaneously at a dose of 5000 IU every 12 h, whereas 12 women received dexamethasone, administered intravenously at a dose of 10 mg every 12 h. Categorical data were evaluated with chi-square and Fisher's exact test; continuous data were analyzed with Mann-Whitney U test; P < .05 was considered significant. In the subgroup treated with heparin the incidence of disseminated intravascular coagulation (DIC) (P < .02), the number of patients requiring blood transfusion (P < .05) and the length of stay at the Intensive Care Unit (ICU) (P < .04) were significantly increased as compared with the subgroup receiving dexamethasone; in this latter subgroup, significantly higher platelet count and hematocrit values, and significantly lower levels of lactate dehydrogenase (LDH) could be documented starting from day 2 after delivery. The results of our investigation suggest that the use of dexamethasone in patients with HELLP syndrome is associated with faster regression and lower incidence of complications in comparison to heparin.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::351309786c9f4ee6440d6800bf7d6772Test
https://doi.org/10.1016/s0049-3848Test(01)00234-1

المؤلفون: Björn Wiman, Anders Winnerkvist, Jarle Vaage, Guro Valen

المصدر: Thrombosis Research. 82:533-542

مصطلحات موضوعية: Male, Cardiac function curve, medicine.medical_specialty, Time Factors, Endothelium, Myocardial Ischemia, Ischemia, Myocardial Reperfusion Injury, In Vitro Techniques, Tissue plasminogen activator, Rats, Sprague-Dawley, Coronary circulation, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, medicine, Animals, cardiovascular diseases, business.industry, Hematology, medicine.disease, Rats, medicine.anatomical_structure, chemistry, Ventricle, Tissue Plasminogen Activator, Reperfusion, Ventricular fibrillation, Cardiology, business, Biomarkers, medicine.drug

الوصف: Tissue plasminogen activator (t-PA) is a potential marker of endothelial cell activation or injury. The relationship between duration of ischaemia and release of t-PA during reperfusion was investigated in isolated rat hearts exposed to either 5, 10, 20, 30, 40, or 60 min of global, normothermic ischaemia followed by 30 min of reperfusion (n = 8 in each group). t-PA activity was measured (chromogenic peptide substrate assay) in the effluent before ischaemia, and after 2.5, 5, 7.5, 10, 20, and 30 min of reperfusion. Release of lactate dehydrogenase (LD), a marker of myocyte injury, was measured before ischaemia and after 5 min reperfusion. Left ventricular pressures were measured by a balloon in the left ventricle. Ischaemia for 20 min or less had only minor effects on cardiac function. Thirty min or more of ischaemia induced ventricular fibrillation during reperfusion in most hearts. After ischaemia t-PA outflow increased, but without any significant difference between groups. Peak release occurred after either 2.5 or 5 min of reperfusion. After 10 min reperfusion the release was not different from the basal value. In contrast, postischaemic release of LD correlated to the length of ischaemia. To conclude, t-PA release from the ischaemic-reperfused rat heart is independent of the length of ischaemia. Thus the potential of t-PA to quantify endothelial injury appears to be limited.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f87f5f719805fe45844b790da5cf659cTest
https://doi.org/10.1016/0049-3848Test(96)00103-x

المؤلفون: F. Seghier, Stig Cronberg, M. Dobrotorá, Jan Stasko, Peter Kubisz

المصدر: Thrombosis Research. 77:145-148

مصطلحات موضوعية: Blood Platelets, Platelet Aggregation, Thrombin Time, Clot Retraction, Clot retraction, Pharmacology, Platelet Factor 3, Platelet Adhesiveness, medicine, Humans, Inducer, Platelet, Cells, Cultured, Teniposide, L-Lactate Dehydrogenase, Chemistry, Hematology, In vitro, Adenosine Diphosphate, Coagulation, Biochemistry, Blood Coagulation Tests, Collagen, Glass, Platelet Aggregation Inhibitors, Platelet factor 4, medicine.drug

الوصف: Teniposide added to citrated platelet-rich plasma reduced platelet aggregation induced by collagen, but did not interfere with ADP-induced aggregation. The availability of platelet factor 3 was decreased irrespective of inducer. Reptilase clot retraction induced by ADP or collagen was reduced. Teniposide did not interfere with platelet adhesion to glass. It did not release lactic dehydrogenase from the cytoplasm of platelets. Coagulation factors were not affected.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0081e6d36f6d5b91b1fbdde1476393edTest
https://doi.org/10.1016/0049-3848Test(95)91620-z

المؤلفون: Fumitomo Koizumi, Chika Yamamoto, Miki Furuya, Hiroshi Kozuka, Toshiyuki Kaji, Michiko Sakamoto

المصدر: Thrombosis Research. 73:255-263

مصطلحات موضوعية: Umbilical Veins, medicine.medical_specialty, Endothelium, medicine.medical_treatment, Basic fibroblast growth factor, Biology, Fibroblast growth factor, Tissue plasminogen activator, Umbilical vein, chemistry.chemical_compound, Internal medicine, medicine, Humans, Aorta, Cells, Cultured, L-Lactate Dehydrogenase, Fibrinolysis, Growth factor, Infant, Newborn, Hematology, Cell biology, Endothelial stem cell, Endocrinology, medicine.anatomical_structure, chemistry, Organ Specificity, Tissue Plasminogen Activator, cardiovascular system, Fibroblast Growth Factor 2, Endothelium, Vascular, Plasminogen activator, medicine.drug

الوصف: Since basic fibroblast growth factor (bFGF) modulates the functions of vascular endothelial cells, we hypothesized that this factor may be involved in the regulation of the blood coagulation-fibrinolytic system mediated by the cells. Confluent cultures of vascular endothelial cells from human umbilical vein were treated with recombinant human bFGF (bFGF) in a serum-free medium and the content of tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by EIA. Treatment with bFGF resulted in a significant decrease in the release of t-PA:Ag from the cells accompanied with a less t-PA activity in the medium. In contrast, the t-PA:Ag release from human aortic endothelial cells was significantly increased by bFGF. The bFGF-induced decrease in the t-PA:Ag release from the venous endothelial cells was completely blocked by anti-bFGF antibody. The incorporation of [3H]leucine into the acid-insoluble fraction of the cells was significantly increased by bFGF; however, the activity of lactate dehydrogenase leaked into the medium was significantly decreased, suggesting that the suppression of the t-PA:Ag release caused by bFGF in the venous endothelial cells was not due to either a nonspecific inhibition of protein synthesis or a nonspecific cell damage. Since bFGF is postulated to be released from damaged endothelial cells, the present data suggest the regulation by bFGF of hemostasis mediated by endothelial cells when the vascular endothelium was damaged.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4652e36bdd5b12e6522b18d5812301eTest
https://doi.org/10.1016/0049-3848Test(94)90104-x

المؤلفون: R Kumari, Madhu Dikshit, Rikhab C. Srimal

المصدر: Thrombosis Research. 69:101-111

مصطلحات موضوعية: Blood Platelets, Male, Neutrophils, medicine.drug_class, Allopurinol, Indomethacin, Pharmacology, Rats, Sprague-Dawley, Superoxide dismutase, chemistry.chemical_compound, Malondialdehyde, Lactate dehydrogenase, medicine, Animals, Platelet, Xanthine oxidase, Lung, Xanthine oxidase inhibitor, biology, Superoxide Dismutase, Free Radical Scavengers, Hematology, Catalase, Rats, chemistry, Biochemistry, Myeloperoxidase, biology.protein, Cyclooxygenase, Pulmonary Embolism, medicine.drug

الوصف: In the present investigation alterations in the free radical generating and scavenging enzymes in platelets, neutrophils (PMNLs), heart and lung homogenates following rat pulmonary thromboembolism have been studied. Thrombosis was induced by intravenous infusion of collagen and adrenaline. Levels of malonaldehyde (MDA) were elevated in the PMNLs after thrombosis. Activities of superoxide dismutase (SOD) and catalase (CAT) were found to increase in platelets and PMNLs respectively. However, there was no significant alteration in the lactate dehydrogenase (LDH), lysozyme (LYS), ratio of xanthine oxidase to dehydrogenase (XO/XH) and PMNLs O 2 − generation before and after thrombosis. Migration of PMNLs following thrombosis was indicated by increased activity of myeloperoxidase (MPO) in the heart. In addition, pretreatment with allopurinol, a xanthine oxidase inhibitor and indomethacin, a cyclooxygenase inhibitor offered protection against thromboembolism induced death/paralysis. Results suggest the involvement of free radicals in thrombosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::daec8202c63fb4189e0d3c112362f97cTest
https://doi.org/10.1016/0049-3848Test(93)90007-b

المؤلفون: Guro Valen, Jarle Vaage, Björn Wiman, Anders Winnerkvist

المصدر: Thrombosis research. 85(3)

مصطلحات موضوعية: Male, medicine.medical_specialty, Endothelium, Bradykinin, In Vitro Techniques, medicine.disease_cause, Tissue plasminogen activator, Ventricular Function, Left, Rats, Sprague-Dawley, chemistry.chemical_compound, Heart Rate, Internal medicine, Lactate dehydrogenase, medicine, Animals, Hydrogen peroxide, L-Lactate Dehydrogenase, T-plasminogen activator, Chemistry, Myocardium, Plasminogen, Hematology, Hydrogen Peroxide, Rats, Oxidative Stress, Endocrinology, medicine.anatomical_structure, Biochemistry, Perfusion, Oxidative stress, medicine.drug

الوصف: To evaluate the potential of tissue plasminogen activator (t-PA) as a marker of endothelial activation or injury, the dose-response relationship between reactive oxygen intermediates and t-PA release was investigated in isolated rat hearts. After stabilization the hearts were perfused for 10 minutes with different concentrations of hydrogen peroxide (H 2 O 2 ) (0 (control perfusion), 20, 40, 80, 120, 160, or 200 μM) (n=8 hearts/group), followed by 30 minutes recovery. Higher concentrations than 80 μM induced cardiac dysfunction and a dose-dependent release of lactate dehydrogenase, indicating myocyte injury. H 2 O 2 -concentrations of 80 μM and more caused a significant, but temporary t-PA release. Peak t-PA release occurred more rapidly with higher concentrations, but otherwise there was no difference dependent on the H 2 O 2 -dose. The effects of H 2 O 2 (120 or 200 μM) on t-PA release were also compared to the effects of bradykinin. Both were given for 10 minutes as above, and the procedure was repeated after 10 minutes recovery. Bradykinin (50 or 500 nM) released t-PA with the same magnitude, but with peak values occurring earlier than t-PA release induced by H 2 O 2 . Bradykinin, but not H 2 O 2 , induced t-PA release during the second exposure, suggesting different mechanisms of release. In conclusion: Perfusion with H 2 O 2 leads to a dose-dependent myocardial injury in isolated rat hearts. H 2 O 2 also causes an acute t-PA release without dose-dependency, suggesting an all or nothing response of the endothelium. t-PA may be used as an indicator of, but cannot quantify endothelial activation or injury. Copyright © 1997 Elsevier Science Ltd

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df32f8ba99a98e20931cc621c32fd0eaTest
https://pubmed.ncbi.nlm.nih.gov/9058499Test