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  1. Artikel ; Online: Alzheimer's Disease: A Systems View Provides a Unifying Explanation of Its Development.

    Grobler, Corlia / van Tongeren, Marvi / Gettemans, Jan / Kell, Douglas B / Pretorius, Etheresia

    Journal of Alzheimer's disease : JAD

    2022  Band 91, Heft 1, Seite(n) 43–70

    Abstract: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting 50 million people globally. It is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles, consisting of amyloid-β and ... ...

    Abstract Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting 50 million people globally. It is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles, consisting of amyloid-β and hyperphosphorylated tau proteins, respectively. Despite global research efforts, there is currently no cure available, due in part to an incomplete understanding of the disease pathogenesis. Numerous possible mechanisms, or hypotheses, explaining the origins of sporadic or late-onset AD have been proposed, including the amyloid-β, inflammatory, vascular, and infectious hypotheses. However, despite ample evidence, the failure of multiple trial drugs at the clinical stage illuminates the possible pitfalls of these hypotheses. Systems biology is a strategy which aims to elucidate the interactions between parts of a whole. Using this approach, the current paper shows how the four previously mentioned hypotheses of AD pathogenesis can be intricately connected. This approach allows for seemingly contradictory evidence to be unified in a system-focused explanation of sporadic AD development. Within this view, it is seen that infectious agents, such as P. gingivalis, may play a central role. The data presented here shows that when present, P. gingivalis or its virulence factors, such as gingipains, may induce or exacerbate pathologies underlying sporadic AD. This evidence supports the view that infectious agents, and specifically P. gingivalis, may be suitable treatment targets in AD.
    Mesh-Begriff(e) Humans ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Neurofibrillary Tangles/pathology ; tau Proteins/metabolism ; Plaque, Amyloid/pathology
    Chemische Substanzen Amyloid beta-Peptides ; tau Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-11-28
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-220720
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes.

    Grobler, Corlia / Maphumulo, Siphosethu C / Grobbelaar, L Mireille / Bredenkamp, Jhade C / Laubscher, Gert J / Lourens, Petrus J / Steenkamp, Janami / Kell, Douglas B / Pretorius, Etheresia

    International journal of molecular sciences

    2020  Band 21, Heft 14

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.
    Mesh-Begriff(e) Betacoronavirus ; Blood Platelets/metabolism ; COVID-19 ; Coronavirus Infections/pathology ; Cytokine Release Syndrome/pathology ; Endothelial Cells/metabolism ; Erythrocytes/metabolism ; Fibrin Fibrinogen Degradation Products/metabolism ; Humans ; P-Selectin/metabolism ; Pandemics ; Pneumonia, Viral/pathology ; Point-of-Care Systems ; Precision Medicine/methods ; SARS-CoV-2 ; Thrombocytopenia/pathology ; Thrombosis/pathology ; von Willebrand Factor/metabolism
    Chemische Substanzen Fibrin Fibrinogen Degradation Products ; P-Selectin ; SELP protein, human ; fibrin fragment D ; von Willebrand Factor
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-07-21
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21145168
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Covid-19

    Corlia Grobler / Siphosethu C. Maphumulo / L. Meirelie Grobbelaar / Jhade C. Bredenkamp / Gert J. Laubscher / Petrus J. Lourens / Janami Steenkamp / Douglas B. Kell / Etheresia Pretorius

    International Journal of Molecular Sciences, Vol 21, Iss 5168, p

    The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

    2020  Band 5168

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.
    Schlagwörter COVID-19 ; fibrin(ogen) ; thrombosis ; bleeding ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2020-07-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

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  4. Artikel: Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

    Grobler, Corlia / Maphumulo, Siphosethu C / Grobbelaar, L Mireille / Bredenkamp, Jhade C / Laubscher, Gert J / Lourens, Petrus J / Steenkamp, Janami / Kell, Douglas B / Pretorius, Etheresia

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.
    Schlagwörter covid19
    Verlag WHO
    Dokumenttyp Artikel
    Anmerkung WHO #Covidence: #670475
    Datenquelle COVID19

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  5. Artikel ; Online: Covid-19

    Grobler, Corlia / Maphumulo, Siphosethu C. / Grobbelaar, L. Mireille / Bredenkamp, Jhade C. / Laubscher, Gert J. / Lourens, Petrus J. / Steenkamp, Janami / Kell, Douglas B. / Pretorius, Etheresia

    the rollercoaster of fibrin(ogen), D-dimer, Von Willebrand Factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes

    2020  

    Abstract: CITATION: Grobler, C. et al. 2020. Covid-19 : the rollercoaster of fibrin(ogen), D-dimer, Von ...

    Abstract CITATION: Grobler, C. et al. 2020. Covid-19 : the rollercoaster of fibrin(ogen), D-dimer, Von Willebrand Factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes. International Journal of Molecular Sciences, 21(14):5168, doi:10.3390/ijms21145168.

    The original publication is available at https://www.mdpi.com

    Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

    Medical Research Council of South Africa (MRC), grant number A0X331

    Self-initiated research and by The Novo Nordisk Foundation, grant number: NNF10CC1016517

    https://www.mdpi.com/1422-0067/21/14/5168

    Publisher's version
    Schlagwörter COVID-19 (Disease) ; Thrombocytopenia ; Blood -- Coagulation ; Thrombosis ; covid19
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2020-07-21
    Verlag MDPI
    Erscheinungsland za
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

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