Predicting Experimental Sepsis Survival with a Mathematical Model of Acute Inflammation
- BiologyFrontiers in Systems Biology
Simulated trajectories of bacteria, inflammatory responses, and damage were closely clustered during the initial stages of infection, suggesting that uncertainty in initial conditions could lead to difficulty in predicting outcomes of sepsis by using inflammation biomarker levels.
THE ACUTE INFLAMMATORY RESPONSE IN DIVERSE SHOCK STATES
A mathematical model incorporating major elements of the acute inflammatory response in C57Bl/6 mice was developed and found that a single model with different initiators including the autonomic system could describe the response to various insults.
A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation.
- BiologyJournal of theoretical biology
MODELING THERAPEUTIC INTERVENTION IN SEPSIS
- Biology, Medicine
Electrical stimulation of the vagus nerve has been shown to attenuate circulating levels of TNF and to reduce organ damage, thus improving survival in experimental models of sepsis, and this work built on a previously published mathematical model of systemic inflammation to qualitatively explore the therapeutic potential.
IN SILICO MODELS OF ACUTE INFLAMMATION IN ANIMALS
- Medicine, BiologyShock
A mathematical model is constructed using ordinary differential equations that encompass the dynamics of cells and cytokines of the acute inflammatory response, as well as global tissue dysfunction and may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously.
Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding.
- Biology, MedicinePhysiological reviews
Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated to provide a framework for understanding the complex and current challenges of managing the septic patient.
General Model of Inflammation
- Biology, MedicineBulletin of mathematical biology
It is found nonaggressive bacteria are able to initiate chronic inflammation and it is proposed why anti-inflammatory cytokine therapy may not be effective in resolving this inflammation.
Deciphering the complexity of acute inflammation using mathematical models
- MedicineImmunologic research
Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.
Sepsis progression and outcome: a dynamical model
- Biology, MedicineTheoretical Biology and Medical Modelling
This work uses the mass-specific rate of blood circulation (SRBC), a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery, and predicts that deviations from normal SRBC correlate with disease progression and adverse outcome.
Mathematical Model of Innate and Adaptive Immunity of Sepsis: A Modeling and Simulation Study of Infectious Disease
- BiologyBioMed research international
Simulated results in silico have shown that adaptive immunity has significant impacts on the outcomes of sepsis progression, and further investigation has found that the intervention timing, intensity of anti-inflammatory cytokines, and initial pathogen load are highly predictive of outcomes of a sepsi episode.
SHOWING 1-10 OF 120 REFERENCES
Inflammatory cell activation in sepsis.
- BiologyBritish medical bulletin
This review focuses on the mechanisms whereby inflammatory cells are activated, how the regulatory system may misfunction and how it may in the future be manipulated to therapeutic advantage.
The pathophysiology and treatment of sepsis.
- MedicineThe New England journal of medicine
This review examines evolving concepts of sepsis and discusses new and potential therapies, including therapy with activated protein C, stringent control of blood glucose, and early goal-directed therapy to treat cellular oxygen deficit.
Anti-inflammatory therapies in sepsis and septic shock
- Medicine, BiologyExpert opinion on investigational drugs
Clinical trials in sepsis have focused on inhibiting specific host pro-inflammatory mediators (e.g., TNF, interleukins) and pooling the results of these trials suggest that this approach has a marginal effect, supporting a role for excessive inflammation inSepsis.
Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality.
- Medicine, BiologyChest
TNF and IL-6 serum levels are higher in septic than in nonseptic shock, but the persistence of TNF andIL-6 in the serum rather than peak levels of cytokines predicts a poor outcome in patients with shock.
Sepsis: a pro- and anti-inflammatory disequilibrium syndrome.
- Biology, MedicineContributions to nephrology
Both the pro- and anti-inflammatory arms have protective and destructive aspects, making their modulation by treatment less predictable than if their actions were purely beneficial or detrimental.
A New Paradigm for the Treatment of Sepsis: Is It Time To Consider Combination Therapy?
- Medicine, BiologyAnnals of Internal Medicine
This study, the largest clinical trial for sepsis to date, randomly assigned more than 3000 patients to receive one of several doses of a Fab component of a monoclonal antibody against tumor necrosis factor (TNF) or placebo and there was a small improvement in mortality that mirrored the data presented in their meta-analysis.
Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation.
- BiologyCritical care medicine
While cytokines are generally viewed as a destructive development in the patient that generally leads to multiple organ dysfunction, cytokines also protect the body when localized and it will be necessary to study the positive effects of cytokines while also studying their role in causing SIRS.
Sepsis Research in the Next Millennium: Concentrate on the Software Rather than the Hardware
It is concluded that sepsis research needs new perspectives that allow it to handle the complex interactions occurring during the disease process and the ideas and techniques of non-linear systems theory are suitable tools for the analysis of complex and dynamic diseases like SIRS and sepsi.
Reducing mortality in sepsis: new directions
- MedicineCritical care
Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis. However, encouraging physicians to put the results of…
Mechanisms of neutrophil‐induced parenchymal cell injury
- Medicine, BiologyJournal of leukocyte biology
This review summarizes recent advances in the understanding of neutrophil‐induced parenchymal cell injury using the liver as an example and discusses the involvement of various adhesion molecules, the role of cytokines and chemokines in the pathophysiology, as well as the effects of proteases and reactive oxygen species released by neutrophils.