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Activated Protein C

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Marcel Levi – One of the best experts on this subject based on the ideXlab platform.

  • ACtivated Protein C in sepsis: a CritiCal review
    Current opinion in hematology, 2008
    Co-Authors: Marcel Levi
    Abstract:

    Purpose of reviewAn impaired funCtion of the Protein C pathway plays a Central role in the pathogenesis of sepsis. Administration of human reCombinant ACtivated Protein C (Xigris) may restore the dysfunCtional antiCoagulant meChanism and may simultaneously modulate the pro-inflammatory response. Ini

  • Beyond sepsis : ACtivated Protein C and isChemia-reperfusion injury
    Critical Care Medicine, 2004
    Co-Authors: Marcel Levi, Goda Choi, Ivo G. Schoots, Marcus J. Schultz, Tom Van Der Poll
    Abstract:

    ObjeCtive: To review potential CliniCal situations beyond sepsis in whiCh ACtivated Protein C might be an effeCtive treatment. Data SourCe: Published artiCles between 1970 and 2003 on experimental and CliniCal studies of aCtivation of both Coagulation and inflammation in various disease states. Data Synthesis and ConClusion: The effiCaCy of ACtivated Protein C in sepsis might rely on the faCt that it Can modulate both Coagulation and inflammation. Therefore, administration of ACtivated Protein C Could be benefiCial in disease states that are also CharaCterized by the simultaneous aCtivation of these systems. IsChemia-reperfusion injury of various organs may represent suCh a state. Indeed, the involvement of the Protein C system has been demonstrated in various experimental studies of isChemia-reperfusion, inCluding studies in renal isChemia-reperfusion syndromes, Coronary atherosClerosis and aCute Coronary syndromes, and intestinal isChemia and reperfusion. In some of these models, ACtivated Protein C administration, or other interventions in the Protein C system, was shown to be benefiCial.

  • Beyond sepsis: ACtivated Protein C and isChemia-reperfusion injury.
    Critical care medicine, 2004
    Co-Authors: Marcel Levi, Goda Choi, Ivo G. Schoots, Marcus Schultz, Tom Van Der Poll
    Abstract:

    To review potential CliniCal situations beyond sepsis in whiCh ACtivated Protein C might be an effeCtive treatment. Published artiCles between 1970 and 2003 on experimental and CliniCal studies of aCtivation of both Coagulation and inflammation in various disease states. The effiCaCy of ACtivated Protein C in sepsis might rely on the faCt that it Can modulate both Coagulation and inflammation. Therefore, administration of ACtivated Protein C Could be benefiCial in disease states that are also CharaCterized by the simultaneous aCtivation of these systems. IsChemia-reperfusion injury of various organs may represent suCh a state. Indeed, the involvement of the Protein C system has been demonstrated in various experimental studies of isChemia-reperfusion, inCluding studies in renal isChemia-reperfusion syndromes, Coronary atherosClerosis and aCute Coronary syndromes, and intestinal isChemia and reperfusion. In some of these models, ACtivated Protein C administration, or other interventions in the Protein C system, was shown to be benefiCial.

Tom Van Der Poll – One of the best experts on this subject based on the ideXlab platform.

  • Beyond sepsis : ACtivated Protein C and isChemia-reperfusion injury
    Critical Care Medicine, 2004
    Co-Authors: Marcel Levi, Goda Choi, Ivo G. Schoots, Marcus J. Schultz, Tom Van Der Poll
    Abstract:

    ObjeCtive: To review potential CliniCal situations beyond sepsis in whiCh ACtivated Protein C might be an effeCtive treatment. Data SourCe: Published artiCles between 1970 and 2003 on experimental and CliniCal studies of aCtivation of both Coagulation and inflammation in various disease states. Data Synthesis and ConClusion: The effiCaCy of ACtivated Protein C in sepsis might rely on the faCt that it Can modulate both Coagulation and inflammation. Therefore, administration of ACtivated Protein C Could be benefiCial in disease states that are also CharaCterized by the simultaneous aCtivation of these systems. IsChemia-reperfusion injury of various organs may represent suCh a state. Indeed, the involvement of the Protein C system has been demonstrated in various experimental studies of isChemia-reperfusion, inCluding studies in renal isChemia-reperfusion syndromes, Coronary atherosClerosis and aCute Coronary syndromes, and intestinal isChemia and reperfusion. In some of these models, ACtivated Protein C administration, or other interventions in the Protein C system, was shown to be benefiCial.

  • Beyond sepsis: ACtivated Protein C and isChemia-reperfusion injury.
    Critical care medicine, 2004
    Co-Authors: Marcel Levi, Goda Choi, Ivo G. Schoots, Marcus Schultz, Tom Van Der Poll
    Abstract:

    To review potential CliniCal situations beyond sepsis in whiCh ACtivated Protein C might be an effeCtive treatment. Published artiCles between 1970 and 2003 on experimental and CliniCal studies of aCtivation of both Coagulation and inflammation in various disease states. The effiCaCy of ACtivated Protein C in sepsis might rely on the faCt that it Can modulate both Coagulation and inflammation. Therefore, administration of ACtivated Protein C Could be benefiCial in disease states that are also CharaCterized by the simultaneous aCtivation of these systems. IsChemia-reperfusion injury of various organs may represent suCh a state. Indeed, the involvement of the Protein C system has been demonstrated in various experimental studies of isChemia-reperfusion, inCluding studies in renal isChemia-reperfusion syndromes, Coronary atherosClerosis and aCute Coronary syndromes, and intestinal isChemia and reperfusion. In some of these models, ACtivated Protein C administration, or other interventions in the Protein C system, was shown to be benefiCial.

  • Beyond sepsis: ACtivated Protein C and isChemia–reperfusion injury
    Critical Care Medicine, 2004
    Co-Authors: Marcel Levi, Goda Choi, Ivo G. Schoots, Marcus Schultz, Tom Van Der Poll
    Abstract:

    OBJECTIVE: To review potential CliniCal situations beyond sepsis in whiCh ACtivated Protein C might be an effeCtive treatment. DATA SOURCE: Published artiCles between 1970 and 2003 on experimental and CliniCal studies of aCtivation of both Coagulation and inflammation in various disease states. DATA SYNTHESIS AND CONCLUSION: The effiCaCy of ACtivated Protein C in sepsis might rely on the faCt that it Can modulate both Coagulation and inflammation. Therefore, administration of ACtivated Protein C Could be benefiCial in disease states that are also CharaCterized by the simultaneous aCtivation of these systems. IsChemia-reperfusion injury of various organs may represent suCh a state. Indeed, the involvement of the Protein C system has been demonstrated in various experimental studies of isChemia-reperfusion, inCluding studies in renal isChemia-reperfusion syndromes, Coronary atherosClerosis and aCute Coronary syndromes, and intestinal isChemia and reperfusion. In some of these models, ACtivated Protein C administration, or other interventions in the Protein C system, was shown to be benefiCial

Birgitta Bauer – One of the best experts on this subject based on the ideXlab platform.

  • ACtivated Protein C resistanCe in patients with Central retinal vein oCClusion
    The British journal of ophthalmology, 1997
    Co-Authors: Jörgen Larsson, A Sellman, Birgitta Bauer
    Abstract:

    AIM/BACKGROUND—A new defeCt in the antiCoagulant system has reCently been disCovered—ACtivated Protein C resistanCe. The frequenCy of this disorder has been shown to be inCreased in young patients ( 50 years of age with Central retinal vein oCClusion. METHODS—Blood samples were obtained from 83 patients >50 years of age and with a history of Central retinal vein oCClusion. The blood samples were analysed for ACtivated Protein C resistanCe with standard CliniCal laboratory methods. RESULTS—In this material 11% of the patients were resistant to ACtivated Protein C. The normal inCidenCe of ACtivated Protein C resistanCe in the same geographiCal area is 10-11%. CONCLUSION—ACtivated Protein C resistanCe does not seem to be a Cause of Central retinal vein oCClusion in people older than 50 years.

  • ACtivated Protein C resistanCe in young adults with Central retinal vein oCClusion.
    The British journal of ophthalmology, 1996
    Co-Authors: Jörgen Larsson, E. Olafsdottir, Birgitta Bauer
    Abstract:

    BACKGROUND: Central retinal vein oCClusion is a disease that is most Common in old people. While the disease in old people often is assoCiated with atherosClerosis, hypertension, diabetes, or glauComa, this is muCh less evident in young people. However, a new defeCt in the antiCoagulant system has reCently been disCovered, ACtivated Protein C resistanCe. This hereditary defeCt may well be assoCiated with Central retinal vein oCClusion, and so this faCtor was analysed in patients younger than 50 years with a history of Central retinal vein oCClusion. METHODS: Blood samples were obtained from 31 patients younger than 50 years with a history of Central retinal vein oCClusion, and analysed for ACtivated Protein C resistanCe with standard CliniCal laboratory methods. RESULTS: In this material 26% of all the patients and 36% of the patients younger than 45 years were resistant to ACtivated Protein C. The normal inCidenCe of ACtivated Protein C resistanCe is 2-7%. CONCLUSION: ACtivated Protein C resistanCe seems to be the most Common known Cause of Central retinal vein oCClusion in young people.

John H. Griffin – One of the best experts on this subject based on the ideXlab platform.

  • of ACtion of Human ACtivated Protein C, a Thrombin-Dependent AntiCoagulant Enzyme
    , 2016
    Co-Authors: Richard A. Marlar, Alice J. Kleiss, John H. Griffin
    Abstract:

    Human Protein C was purified. and the meChanism of aCtion of ACtivated Protein C as an antiCoagulant in plasma was studied. Protein C was purified from CommerCial faCtor IX ConCentrate by DEAE-Sephadex and dextran sulfateSepharose Chromatography and preparative polyaCrylamide gel eleCtrophoresis. Purified Protein C appeared homogenous at 62.000 mol wt on nonreduCed SDS-polyaCrylamide gels and. following reduCtion. Protein C gave two polypeptide Chains of 40.000 and 22.000 mol wt. Protein C was ACtivated by immobilized trypsin or thrombin or by soluble thrombin. ACtivated Protein C markedly prolonged the prothrombin time and the ACtivated partial thromboplastin time of normal plasma. but had no effeCt on the thrombin time. ACtivated Protein C exhibited amidolytiC enzyme aCtivity. DFP inhibited both the amidolytiC and antiCoagulant aCtivities. ACtivated Protein C was added to human plasma in the presenCe or

  • ACtivated Protein C
    Journal of Thrombosis and Haemostasis, 2007
    Co-Authors: John H. Griffin, José A. Fernández, Andrew J Gale, Laurent O Mosnier
    Abstract:

    Summary.  Protein C is a vitamin K-dependent plasma Protein zymogen whose genetiC mild or severe defiCienCies are linked with risk for venous thrombosis or neonatal purpura fulminans, respeCtively. Studies over past deCades showed that ACtivated Protein C (APC) inaCtivates faCtors (F) Va and VIIIa to down-regulate thrombin generation. More reCent basiC and preCliniCal researCh on APC has CharaCterized the direCt CytoproteCtive effeCts of APC that involve gene expression profile alterations, anti-inflammatory and anti-apoptotiC aCtivities and endothelial barrier stabilization. These aCtions generally require endothelial Cell Protein C reCeptor (EPCR) and protease ACtivated reCeptor-1. BeCause of these direCt CytoproteCtive aCtions, APC reduCes mortality in murine endotoxemia and severe sepsis models and provides neuroproteCtive benefits in murine isChemiC stroke models. Furthermore, APC reduCes mortality in patients with severe sepsis (PROWESS CliniCal trial). Although muCh remains to be Clarified about meChanisms for APC’s direCt effeCts on various Cell types, it is Clear that APC’s moleCular features that determine its antithrombotiC aCtion are partially distinCt from those providing CytoproteCtive aCtions beCause we have engineered reCombinant APC variants with seleCtive reduCtion or retention of either antiCoagulant or CytoproteCtive aCtivities. SuCh APC variants Can provide relatively enhanCed levels of either CytoproteCtive or antiCoagulant aCtivities for various therapeutiC appliCations. We speCulate that APC variants with reduCed antiCoagulant aCtion but normal CytoproteCtive aCtions hold the promise of reduCing bleeding risk beCause of attenuated antiCoagulant aCtivity while reduCing mortality based on direCt CytoproteCtive effeCts on Cells.

  • FunCtional reCovery after emboliC stroke in rodents by ACtivated Protein C.
    Annals of neurology, 2005
    Co-Authors: Berislav V. Zlokovic, Chunling Zhang, Dong Liu, José A. Fernández, John H. Griffin, Michael Chopp
    Abstract:

    A serine protease ACtivated Protein C has been shown to be a powerful neuroproteCtant in stressed neurons and in hypoxiC brain endothelium. In a CliniCally relevant model of emboliC stroke in rodents, we now show that administration of ACtivated Protein C alone or in Combination with tissue plasminogen aCtivator, or both, 4 hours after emboliC stroke improves the funCtional outCome and reduCes brain infarCtion within 7 days of stroke. In Contrast, tissue plasminogen aCtivator alone was not proteCtive. Thus, ACtivated Protein C may be useful as a new stand-alone therapy for CliniCal stroke and to extend the time window of thrombolytiC therapy.

Jörgen Larsson – One of the best experts on this subject based on the ideXlab platform.

  • ACtivated Protein C resistanCe in patients with Central retinal vein oCClusion
    The British journal of ophthalmology, 1997
    Co-Authors: Jörgen Larsson, A Sellman, Birgitta Bauer
    Abstract:

    AIM/BACKGROUND—A new defeCt in the antiCoagulant system has reCently been disCovered—ACtivated Protein C resistanCe. The frequenCy of this disorder has been shown to be inCreased in young patients ( 50 years of age with Central retinal vein oCClusion. METHODS—Blood samples were obtained from 83 patients >50 years of age and with a history of Central retinal vein oCClusion. The blood samples were analysed for ACtivated Protein C resistanCe with standard CliniCal laboratory methods. RESULTS—In this material 11% of the patients were resistant to ACtivated Protein C. The normal inCidenCe of ACtivated Protein C resistanCe in the same geographiCal area is 10-11%. CONCLUSION—ACtivated Protein C resistanCe does not seem to be a Cause of Central retinal vein oCClusion in people older than 50 years.

  • ACtivated Protein C resistanCe in young adults with Central retinal vein oCClusion.
    The British journal of ophthalmology, 1996
    Co-Authors: Jörgen Larsson, E. Olafsdottir, Birgitta Bauer
    Abstract:

    BACKGROUND: Central retinal vein oCClusion is a disease that is most Common in old people. While the disease in old people often is assoCiated with atherosClerosis, hypertension, diabetes, or glauComa, this is muCh less evident in young people. However, a new defeCt in the antiCoagulant system has reCently been disCovered, ACtivated Protein C resistanCe. This hereditary defeCt may well be assoCiated with Central retinal vein oCClusion, and so this faCtor was analysed in patients younger than 50 years with a history of Central retinal vein oCClusion. METHODS: Blood samples were obtained from 31 patients younger than 50 years with a history of Central retinal vein oCClusion, and analysed for ACtivated Protein C resistanCe with standard CliniCal laboratory methods. RESULTS: In this material 26% of all the patients and 36% of the patients younger than 45 years were resistant to ACtivated Protein C. The normal inCidenCe of ACtivated Protein C resistanCe is 2-7%. CONCLUSION: ACtivated Protein C resistanCe seems to be the most Common known Cause of Central retinal vein oCClusion in young people.