LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article: Role of activated protein C in the pathophysiology of severe sepsis.

Dettenmeier, Patricia / Swindell, Bridget / Stroud, Mary / Arkins, Nancy / Howard, April

American journal of critical care : an official publication, American Association of Critical-Care Nurses

2003 Volume 12, Issue 6, Page(s) 518–24; quiz 525–6

Abstract: ... protein C, in patients with severe sepsis. The nursing implications of this new approved therapy are ... being researched and developed. The epidemiology, pathophysiology, and treatment of severe sepsis are ... With increased understanding of the pathophysiology of sepsis, particularly the intricate interplay between ...

Abstract	Sepsis is a complex syndrome that can lead to multiple organ failure and death. Severe sepsis has been associated with mortality rates ranging from 28% to 50% and is the most common cause of death in the noncardiac intensive care unit. Despite advances in both antibiotic therapy and supportive care, the mortality rate due to severe sepsis has remained fundamentally unchanged in the past several decades. With increased understanding of the pathophysiology of sepsis, particularly the intricate interplay between activation of coagulation and inflammation, novel therapeutic agents that may improve clinical outcomes are being researched and developed. The epidemiology, pathophysiology, and treatment of severe sepsis are reviewed. Also discussed are the recently published results from a multicenter, randomized, placebo-controlled phase 3 clinical trial of drotrecogin alfa (activated), a recombinant form of human activated protein C, in patients with severe sepsis. The nursing implications of this new approved therapy are discussed.
MeSH term(s)	Anti-Infective Agents/adverse effects ; Anti-Infective Agents/therapeutic use ; Anticoagulants/adverse effects ; Anticoagulants/therapeutic use ; Contraindications ; Hemorrhage/chemically induced ; Humans ; Protein C/adverse effects ; Protein C/therapeutic use ; Recombinant Proteins/adverse effects ; Recombinant Proteins/therapeutic use ; Sepsis/diagnosis ; Sepsis/drug therapy ; Sepsis/pathology ; Severity of Illness Index
Chemical Substances	Anti-Infective Agents ; Anticoagulants ; Protein C ; Recombinant Proteins ; drotrecogin alfa activated (JGH8MYC891)
Language	English
Publishing date	2003-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1130987-8
ISSN	1062-3264
ISSN	1062-3264
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3502: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: [Study progress of role of co-suppressor molecules in sepsis immune dysfunction].

Gao, Jinghua / Liu, Zheying / Liu, Zhifeng

Zhonghua wei zhong bing ji jiu yi xue

2020 Volume 32, Issue 1, Page(s) 121–125

Abstract: ... treatment of sepsis immune dysfunction, this article mainly summarizes the new findings on the role ... response to infection. The pathophysiology core issue is that the body initiates a severe inflammatory ... mucin-containing protein-3 (TIM-3), cytotoxic T lymphocyte associated antigen-4 (CTLA-4 ...

Abstract	Objective: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The pathophysiology core issue is that the body initiates a severe inflammatory reaction in response to the invasion of pathogenic microorganisms at the initial stage of disease. Subsequently, the body begins to fight inflammation in order to balance immunity status and eventually induces the immune paralysis or immunosuppressive state characterized by exhaustion of immune cell. Both in innate immunity and in acquired immunity, some co-suppressor molecules on the surface of immune cells play important roles in immunosuppression, such as, programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin-containing protein-3 (TIM-3), cytotoxic T lymphocyte associated antigen-4 (CTLA-4), natural killer cell receptor 2B4 (CD244), B and T lymphocyte attenuator (BTLA) and NKG2A (CD94), et al. Blocking the interaction between these co-suppressor molecules and their ligands can significantly reverse the immunosuppressive state in septic animal models or patients. In order to provide a reference for the monitoring and treatment of sepsis immune dysfunction, this article mainly summarizes the new findings on the role of those co-suppressor molecules in sepsis immune dysfunction in recent years.
MeSH term(s)	Adaptive Immunity ; Animals ; CTLA-4 Antigen ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Immunity, Innate ; Ligands ; NK Cell Lectin-Like Receptor Subfamily C ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic ; Sepsis/immunology ; Sepsis/physiopathology ; Signaling Lymphocytic Activation Molecule Family
Chemical Substances	BTLA protein, human ; CD244 protein, human ; CTLA-4 Antigen ; HAVCR2 protein, human ; Hepatitis A Virus Cellular Receptor 2 ; KLRC1 protein, human ; Ligands ; NK Cell Lectin-Like Receptor Subfamily C ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic ; Signaling Lymphocytic Activation Molecule Family
Language	Chinese
Publishing date	2020-04-08
Publishing country	China
Document type	Journal Article ; Review
ISSN	2095-4352
ISSN	2095-4352
DOI	10.3760/cma.j.cn121430-20190916-00023
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: The Role of Protein C in Sepsis.

Looney, Mark R. / Matthay, Michael A.

Current infectious disease reports

2008 Volume 3, Issue 5, Page(s) 413–418

Abstract: ... importantly, in a recently completed large, randomized trial of activated protein C treatment in severe sepsis ... proinflammatory pathways in sepsis. Protein C, a natural anticoagulant, interrupts several of the pathophysiologic ... pathways in sepsis. Acquired protein C deficiency is present in the majority of septic patients and is ...

Abstract	During the past 15 years, several anti-inflammatory treatments have failed to reduce mortality in patients with severe sepsis. However, recent evidence indicates that coagulation abnormalities in sepsis may play a major role in the pathogenesis of multiple organ failure and the high mortality rate in patients with severe sepsis. Interestingly, blockade of the coagulant pathway can inhibit both procoagulant and proinflammatory pathways in sepsis. Protein C, a natural anticoagulant, interrupts several of the pathophysiologic pathways in sepsis. Acquired protein C deficiency is present in the majority of septic patients and is associated with unfavorable outcomes. Protein C replacement therapy was effective in preclinical animal models of sepsis in reducing end-organ damage and mortality. Recent clinical trials of protein C replacement in human meningococcemia resulted in a markedly decreased morbidity and mortality. And, most importantly, in a recently completed large, randomized trial of activated protein C treatment in severe sepsis, mortality was reduced from 30.8% in the placebo group to 24.7% in the treatment group at 28 days. Thus, there is new evidence that mortality can be reduced among patients with severe sepsis through the use of a new therapy that inhibits the procoagulant and the inflammatory cascades.
Language	English
Publishing date	2008-10-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2019948-X
ISSN	1534-3146 ; 1523-3847
ISSN (online)	1534-3146
ISSN	1523-3847
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5519: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The role of Nox2-derived ROS in the development of cognitive impairment after sepsis.

Hernandes, Marina S / D'Avila, Joana C / Trevelin, Silvia C / Reis, Patricia A / Kinjo, Erika R / Lopes, Lucia R / Castro-Faria-Neto, Hugo C / Cunha, Fernando Q / Britto, Luiz R G / Bozza, Fernando A

Journal of neuroinflammation

2014 Volume 11, Page(s) 36

Abstract: Background: Sepsis- associated encephalopathy (SAE) is an early and common feature of severe ... infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal ... cognitive impairment of sepsis survivors.: Methods: Sepsis was induced in WT and gp91(phox) knockout mice ...

Abstract	Background: Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. Methods: Sepsis was induced in WT and gp91(phox) knockout mice (gp91(phox-/-)) by cecal ligation and puncture (CLP) to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene expression and neuroinflammation in the hippocampus at six hours, twenty-four hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with the inhibitory avoidance test and the Morris water maze in control and apocynin-treated WT mice. Results: Acute oxidative damage to the hippocampus was identified by increased 4-HNE expression in parallel with an increase in Nox2 gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin completely inhibited hippocampal oxidative stress in septic animals. Pharmacologic inhibition or the absence of Nox2 in gp91(phox-/-) mice prevented glial cell activation, one of the central mechanisms associated with SAE. Finally, treatment with apocynin and inhibition of hippocampal oxidative stress in the acute phase of sepsis prevented the development of long-term cognitive impairment. Conclusions: Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE.
MeSH term(s)	Acetophenones/therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Avoidance Learning/drug effects ; Bacterial Proteins/metabolism ; Chemokine CCL2/metabolism ; Cognition Disorders/etiology ; Disease Models, Animal ; Hippocampus/metabolism ; Hippocampus/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; NADH, NADPH Oxidoreductases/metabolism ; NADPH Oxidases/metabolism ; Reactive Oxygen Species/metabolism ; Receptors, Immunologic/deficiency ; Sepsis/complications ; Sepsis/drug therapy ; Sepsis/pathology ; Typhlitis/complications ; Typhlitis/etiology
Chemical Substances	Acetophenones ; Anti-Inflammatory Agents, Non-Steroidal ; Bacterial Proteins ; Ccl2 protein, mouse ; Chemokine CCL2 ; Pirb protein, mouse ; Reactive Oxygen Species ; Receptors, Immunologic ; acetovanillone (B6J7B9UDTR) ; NADH, NADPH Oxidoreductases (EC 1.6.-) ; NADPH Oxidases (EC 1.6.3.-) ; Nox-2 protein, bacteria (EC 1.6.99.-)
Language	English
Publishing date	2014-02-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1742-2094
ISSN (online)	1742-2094
DOI	10.1186/1742-2094-11-36
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Role of the tissue factor pathway in the pathogenesis and management of multiple organ failure.

Smithies, Mark N / Weaver, Christine B

Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

2004 Volume 15 Suppl 1, Page(s) S11–20

Abstract: ... potential anticoagulant therapies: antithrombin III, activated protein C, and tissue factor pathway ... worldwide, severe sepsis is also associated with a considerable cost burden that places significant strain ... therefore of vital importance to today's intensive care physicians. This paper will examine the pathophysiology ...

Abstract	Sepsis is caused by a dysregulated immune response to infection and, without intervention, can lead to septic shock and multiple organ failure. A leading cause of morbidity and mortality in intensive care units worldwide, severe sepsis is also associated with a considerable cost burden that places significant strain on global healthcare budgets. The development of an efficacious and cost-effective treatment strategy is therefore of vital importance to today's intensive care physicians. This paper will examine the pathophysiology of sepsis and multiple organ dysfunction before reviewing trials recently undertaken to investigate three potential anticoagulant therapies: antithrombin III, activated protein C, and tissue factor pathway inhibitor. Finally, other recent developments in the care of sepsis patients will be briefly examined.
MeSH term(s)	Anticoagulants/therapeutic use ; Disease Management ; Humans ; Multiple Organ Failure/etiology ; Multiple Organ Failure/therapy ; Sepsis/complications ; Sepsis/therapy ; Thromboplastin/metabolism ; Thromboplastin/physiology ; Treatment Outcome
Chemical Substances	Anticoagulants ; Thromboplastin (9035-58-9)
Language	English
Publishing date	2004-03-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1033551-1
ISSN	0957-5235
ISSN	0957-5235
DOI	10.1097/00001721-200405001-00003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2920: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock.

Pathan, Nazima / Hemingway, Cheryl A / Alizadeh, Ash A / Stephens, Alick C / Boldrick, Jennifer C / Oragui, Emmanuelle E / McCabe, Colm / Welch, Steven B / Whitney, Adeline / O'Gara, Peter / Nadel, Simon / Relman, David A / Harding, Sian E / Levin, Michael

Lancet (London, England)

2004 Volume 363, Issue 9404, Page(s) 203–209

Abstract: Background: Myocardial failure has a central role in the complex pathophysiology of septic ... with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal ... of a myocardial depressant factor--specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset ...

Abstract	Background: Myocardial failure has a central role in the complex pathophysiology of septic shock and contributes to organ failure and death. During the sepsis-induced inflammatory process, specific factors are released that depress myocardial contractile function. We aimed to identify these mediators of myocardial depression in meningococcal septic shock. Methods: We combined gene-expression profiling with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal septic shock. We identified genes that were significantly upregulated in blood after exposure to meningococci. We then selected for further analysis those genes whose protein products had properties of a myocardial depressant factor--specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset of meningococcal infection. Findings: We identified 174 significantly upregulated genes in meningococcus-infected blood: six encoded proteins that were of the predicted size and had characteristics of a myocardial depressant factor. Of these, interleukin 6 caused significant myocardial depression in vitro. Removal of interleukin 6 from serum samples of patients with meningococcaemia and from supernatants of inflammatory cells stimulated by meningococci in vitro abolished the negative inotropic activity. Furthermore, concentrations in serum of interleukin 6 strongly predicted degree of myocardial dysfunction and severity of disease in children with meningococcal septic shock. Interpretation: Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies.
MeSH term(s)	Adult ; Animals ; Cardiac Output, Low/blood ; Cardiac Output, Low/physiopathology ; Cardiomyopathies/blood ; Cardiomyopathies/physiopathology ; Cytokines/blood ; Cytokines/physiology ; Humans ; In Vitro Techniques ; Interleukin-6/blood ; Interleukin-6/physiology ; Male ; Meningococcal Infections/blood ; Meningococcal Infections/physiopathology ; Myocardial Contraction/physiology ; Myocardial Depressant Factor/blood ; Myocardial Depressant Factor/physiology ; Oligonucleotide Array Sequence Analysis ; Rats ; Rats, Sprague-Dawley ; Shock, Septic/blood ; Shock, Septic/physiopathology
Chemical Substances	Cytokines ; Interleukin-6 ; Myocardial Depressant Factor
Language	English
Publishing date	2004-01-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(03)15326-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.5: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 94: Show issues

Order via subito

Details ▾

Article: Coagulation in severe sepsis: a central role for thrombomodulin and activated protein C.

Faust, S N / Heyderman, R S / Levin, M

Critical care medicine

2001 Volume 29, Issue 7 Suppl, Page(s) S62–7; discussion S67–8

Abstract: ... Conclusions: The plasma components of the protein C pathway are down-regulated in sepsis. Decreased ... of the protein C pathway and thrombomodulin.: Data sources/study selection: Published research abstracts and ... review articles on the experimental and clinical investigation of the pathophysiology ...

Abstract	Objectives: To review the mechanisms that cause coagulation abnormalities in sepsis, focusing on the interaction between the vascular endothelium and the circulating coagulation factors, particularly the role of the protein C pathway and thrombomodulin. Data sources/study selection: Published research abstracts and review articles on the experimental and clinical investigation of the pathophysiology of disseminated intravascular coagulation in sepsis. Data extraction and synthesis: The data provide increasing evidence that the coagulopathy seen in sepsis is a result of a complex imbalance of pro- and anticoagulant pathways. Whereas previous research has largely studied events in the plasma, it is now apparent that reactions on cell surfaces such as the vascular endothelium are important in the control of the regulatory pathways. Conclusions: The plasma components of the protein C pathway are down-regulated in sepsis. Decreased thrombomodulin expression may cause defective function of the endothelial component of this pathway in septic patients. Treatments must be designed to overcome any functional defect.
MeSH term(s)	Anticoagulants/therapeutic use ; Blood Coagulation Factors/physiology ; Blood Platelets/physiology ; Disease Susceptibility ; Disseminated Intravascular Coagulation/blood ; Disseminated Intravascular Coagulation/immunology ; Disseminated Intravascular Coagulation/microbiology ; Disseminated Intravascular Coagulation/physiopathology ; Down-Regulation/physiology ; Fibrinolysis/physiology ; Humans ; Inflammation ; Protein C/physiology ; Protein C/therapeutic use ; Sepsis/complications ; Sepsis/drug therapy ; Sepsis/immunology ; Severity of Illness Index ; Thrombomodulin/chemistry ; Thrombomodulin/physiology ; Thrombomodulin/therapeutic use ; Vasoconstriction/physiology
Chemical Substances	Anticoagulants ; Blood Coagulation Factors ; Protein C ; Thrombomodulin
Language	English
Publishing date	2001-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/00003246-200107001-00022
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1261: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation.

Finigan, James H / Dudek, Steven M / Singleton, Patrick A / Chiang, Eddie T / Jacobson, Jeffrey R / Camp, Sara M / Ye, Shiu Q / Garcia, Joe G N

The Journal of biological chemistry

2005 Volume 280, Issue 17, Page(s) 17286–17293

Abstract: ... syndromes such as sepsis and acute lung injury (ALI). Activated protein C (APC), a serine protease critically involved ... between endothelial protein C receptor (EPCR) and S1P1, the receptors for APC and S1P, respectively. EPCR ... components potentially critical to the improved survival of APC-treated patients with severe sepsis. ...

Abstract	Increased endothelial cell (EC) permeability is central to the pathophysiology of inflammatory syndromes such as sepsis and acute lung injury (ALI). Activated protein C (APC), a serine protease critically involved in the regulation of coagulation and inflammatory processes, improves sepsis survival through an unknown mechanism. We hypothesized a direct effect of APC to both prevent increased EC permeability and to restore vascular integrity after edemagenic agonists. We measured changes in transendothelial electrical resistance (TER) and observed that APC produced concentration-dependent attenuation of TER reductions evoked by thrombin. We next explored known EC barrier-protective signaling pathways and observed dose-dependent APC-mediated increases in cortical myosin light chain (MLC) phosphorylation in concert with cortically distributed actin polymerization, findings highly suggestive of Rac GTPase involvement. We next determined that APC directly increases Rac1 activity, with inhibition of Rac1 activity significantly attenuating APC-mediated barrier protection to thrombin challenge. Finally, as these signaling events were similar to those evoked by the potent EC barrier-enhancing agonist, sphingosine 1-phosphate (S1P), we explored potential cross-talk between endothelial protein C receptor (EPCR) and S1P1, the receptors for APC and S1P, respectively. EPCR-blocking antibody (RCR-252) significantly attenuated both APC-mediated barrier protection and increased MLC phosphorylation. We next observed rapid, EPCR and PI 3-kinase-dependent, APC-mediated phosphorylation of S1P1 on threonine residues consistent with S1P1 receptor activation. Co-immunoprecipitation studies demonstrate an interaction between EPCR and S1P1 upon APC treatment. Targeted silencing of S1P1 expression using siRNA significantly reduced APC-mediated barrier protection against thrombin. These data suggest that novel EPCR ligation and S1P1 transactivation results in EC cytoskeletal rearrangement and barrier protection, components potentially critical to the improved survival of APC-treated patients with severe sepsis.
MeSH term(s)	Actins/metabolism ; Blood Coagulation Factors/chemistry ; Blood Coagulation Factors/metabolism ; Cells, Cultured ; Cytoskeleton/metabolism ; Dose-Response Relationship, Drug ; Electric Impedance ; Endothelium/metabolism ; Endothelium/pathology ; Endothelium, Vascular/metabolism ; Genes, Dominant ; Humans ; Immunoprecipitation ; Lung/metabolism ; Lung/pathology ; Microscopy, Fluorescence ; Models, Biological ; Myosin Light Chains/chemistry ; Phosphorylation ; Protein Binding ; Protein C/metabolism ; RNA, Small Interfering/metabolism ; Receptors, Cell Surface/chemistry ; Receptors, Cell Surface/metabolism ; Receptors, Lysosphingolipid/metabolism ; Sepsis/metabolism ; Serine/chemistry ; Signal Transduction ; Threonine/chemistry ; Thrombin/metabolism ; Time Factors ; Transcriptional Activation ; Transfection ; rac GTP-Binding Proteins/metabolism ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	Actins ; Blood Coagulation Factors ; Myosin Light Chains ; Protein C ; RNA, Small Interfering ; Receptors, Cell Surface ; Receptors, Lysosphingolipid ; activated protein C receptor ; Threonine (2ZD004190S) ; Serine (452VLY9402) ; Thrombin (EC 3.4.21.5) ; rac GTP-Binding Proteins (EC 3.6.5.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2005-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M412427200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Recombinant human activated protein C for the treatment of severe sepsis: is there a role in pediatrics?

Giroir, Brett P

Current opinion in pediatrics

2003 Volume 15, Issue 1, Page(s) 92–96

Abstract: ... Recently, recombinant activated protein C was shown to reduce the mortality of adults with severe sepsis ... mortality among children. The clinical pathophysiology of severe sepsis reflects a coordinated activation ... of children and adults with severe sepsis develop acquired deficiency of protein C because of factor ...

Abstract	Sepsis with organ failure (severe sepsis) remains an important cause of morbidity and mortality among children. The clinical pathophysiology of severe sepsis reflects a coordinated activation of the innate immune response, including elaboration of proinflammatory cytokines and the induction of the extrinsic pathway of coagulation (sepsis-induced coagulopathy). These proinflammatory and procoagulant pathways are linked, and are similarly coregulated by a number of proteins and factors, including protein C. However, at least 80% of children and adults with severe sepsis develop acquired deficiency of protein C because of factor consumption. This deficiency is associated with poor outcomes, including multiple organ failure and mortality. Recently, recombinant activated protein C was shown to reduce the mortality of adults with severe sepsis, and is now approved for such use in the United States and Europe. The rationale for pediatric applications of protein C and ongoing clinical trials in children are reviewed.
MeSH term(s)	Adult ; Age Factors ; Anticoagulants/adverse effects ; Anticoagulants/pharmacology ; Anticoagulants/therapeutic use ; Child ; Humans ; Protein C/adverse effects ; Protein C/pharmacology ; Protein C/therapeutic use ; Recombinant Proteins/adverse effects ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Sepsis/drug therapy ; Severity of Illness Index
Chemical Substances	Anticoagulants ; Protein C ; Recombinant Proteins
Language	English
Publishing date	2003-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1049374-8
ISSN	1531-698X ; 1040-8703
ISSN (online)	1531-698X
ISSN	1040-8703
DOI	10.1097/00008480-200302000-00015
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3049: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Critical role of CD14 for production of proinflammatory cytokines and cytokine inhibitors during sepsis with failure to alter morbidity or mortality.

Ebong, S J / Goyert, S M / Nemzek, J A / Kim, J / Bolgos, G L / Remick, D G

Infection and immunity

2001 Volume 69, Issue 4, Page(s) 2099–2106

Abstract: ... test the role of CD14 in the inflammatory response to sepsis and to ascertain if alterations would ... that the CD14 pathway of activation plays a critical role in the production of both pro-inflammatory cytokines ... We investigated the immunopathophysiologic responses during sepsis induced by cecal ligation and ...

Abstract	We investigated the immunopathophysiologic responses during sepsis induced by cecal ligation and puncture (CLP) in CD4-deficient (CD14 knockout [CD14KO]) mice. Our studies were designed to specifically test the role of CD14 in the inflammatory response to sepsis and to ascertain if alterations would improve morbidity or mortality. Sepsis was induced using the CLP model with appropriate antibiotic treatment. The severity of sepsis increased in the CD14KO mice with increasing puncture size (18 gauge [18G], 21G, and 25G). Following CLP, body temperature (at 12 h) and gross motor activity levels of the sham and 25G CLP groups recovered to normal, while the 21G and 18G CLP groups exhibited severe hypothermia coupled with decreased gross motor activity and body weight. There were no significant differences in survival, temperature, body weight, or activity levels between CD14KO and control mice after 21G CLP. However, CD14KO mice expressed two- to fourfold less pro-inflammatory (interleukin-1beta [IL-1beta], tumor necrosis factor [TNF], and IL-6) and anti-inflammatory (IL-10, IL-1 receptor antagonist, and TNF receptors I and II) cytokines in the blood after 21G CLP. Plasma levels of the chemokines macrophage inflammatory protein 2alpha and KC were similarly reduced in CD14KO mice. A similar trend of decreased cytokine and cytokine inhibitor levels was observed in the peritoneal cavity of CD14KO mice. Our results indicate that the CD14 pathway of activation plays a critical role in the production of both pro-inflammatory cytokines and cytokine inhibitors but has minimal impact on the morbidity or mortality induced by the CLP model of sepsis.
MeSH term(s)	Animals ; Body Temperature ; Chemokines/blood ; Cytokines/biosynthesis ; Interleukin 1 Receptor Antagonist Protein ; Lipopolysaccharide Receptors/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; Receptors, Tumor Necrosis Factor/analysis ; Sepsis/immunology ; Sepsis/mortality ; Sepsis/physiopathology ; Sialoglycoproteins/analysis
Chemical Substances	Chemokines ; Cytokines ; Il1rn protein, mouse ; Interleukin 1 Receptor Antagonist Protein ; Lipopolysaccharide Receptors ; Receptors, Tumor Necrosis Factor ; Sialoglycoproteins
Language	English
Publishing date	2001-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.69.4.2099-2106.2001
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.A 684: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito