Pathophysiology of Mifepristone-Induced Septic Shock Due to Clostridium sordellii

2005 ◽  
Vol 39 (9) ◽  
pp. 1483-1488 ◽  
Author(s):  
Ralph P Miech
Keyword(s):  
Septic Shock ◽  
Immune System ◽  
Innate Immune System ◽  
Glucocorticoid Receptors ◽  
Data Extraction ◽  
Rapid Development ◽  
Innate Immune ◽  
Data Sources ◽  
Clostridium Sordellii ◽  
Cytokine Responses

OBJECTIVE: To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii. DATA SOURCES: MEDLINE, PubMed, and Google Scholar databases were searched (1984–March 2005%). Key search terms were mifepristone, RU38486, RU486, Mifeprex, medical abortion, septic shock, innate immune system, cytokines, and Clostridium sordellii. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathophysiology of mifepristone-induced septic shock due to C. sordellii. DATA SYNTHESIS: The mechanisms of action of mifepristone were incorporated into the pathophysiology of septic shock due to C. sordellii. Mifepristone, by blocking both progesterone and glucocorticoid receptors, interferes with the controlled release and functioning of cortisol and cytokines. Failure of physiologically controlled cortisol and cytokine responses results in an impaired innate immune system that results in disintegration of the body's defense system necessary to prevent the endometrial spread of C. sordellii infection. The abnormal cortisol and cytokine responses due to mifepristone coupled to the release of potent exotoxins and an endotoxin from C. sordellii are the major contributors to the rapid development of lethal septic shock. CONCLUSIONS: Theoretically, it appears that the mechanisms of mifepristone action favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock.

scholarly journals Corticosteroid in Septic Shock: Advantage or Disadvantage?

2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Sakura Muhammad Tola
Keyword(s):  
Septic Shock ◽  
Immune System ◽  
Inflammatory Disease ◽  
Adjunctive Therapy ◽  
Innate Immune System ◽  
Innate Immune ◽  
Hemodynamic Stability ◽  
Major Health ◽  
Major Health Issue ◽  
Multi Organ Dysfunction Syndrome

Sepsis has become a major health issue, with more patients dying in hospitals due to sepsis related complications. The pathogenesis of sepsis is complex and involves multiple aspects of the interaction between the infecting microorganisms and the host. Sepsis is fundamentally an inflammatory disease mediated by the activation of the innate immune system. In the case, sepsis is an unbalanced (proinflammatory and anti-inflammatory), dysregulated response, the localized process goes out of control and becomes systemic contribute to diminished oxygen delivery. The process also leads to decreased hemodynamic stability, hyperglycemia and ultimately, multi organ dysfunction syndrome and death in septic shock. The use of corticosteroid hydrocortisone as adjunctive therapy is still debating due to the lack of supporting study and differences result among the studies.

scholarly journals Becoming Archaea: Septic Shock, Warburg effect and loss of endosymbiotic relation-Billion year war of two genomes

2017 ◽  
Author(s):  
Vasanthakumar Natesan
Keyword(s):  
Septic Shock ◽  
Immune System ◽  
Mitochondrial Genome ◽  
Mitochondrial Respiration ◽  
Innate Immune System ◽  
Warburg Effect ◽  
Nuclear Genome ◽  
Eukaryotic Cell ◽  
Innate Immune ◽  
Molecular Pattern

Becoming Archaea: Septic Shock, Warburg effect and loss of endosymbiotic relation-Billion year war of two genomes.ABSTRACT : Septic shock is a major problem in medicine and carries high mortality rate. Irrespective of the advances in this field the underlying mechanism behind septic shock still remains a mystery. To understand septic shock we need to understand the evolution of eukaryotic cell and the billion year war between archaeal/nuclear genome and the bacterial/mitochondrial genome. The ancient infection of archaeal host by the bacteria (α-proteobacteria) resulted in the formation of eukaryotes and mitochondrial endosymbiont occurred >1.5 billion years ago and this extraordinary event is occurring from then on all the time till now resulted in formation of complex life forms. In this article I propose ‘Warburg common pathogenesis evolutionary model’, which has the potential to explain septic shock and most of the pathophysiological processes. I hypothesize that the bacterial/mitochondrial invasion of the eukaryote cell is supported by the mitochondrial system of the host eukaryotic cell and resisted by the innate immune system which is the archaeal part of the host eukaryotic cell, as archaea is the real host before it became eukaryote.Three major outcomes may result because of the bacterial /mitochondrial invasion related event,1) PAMP/DAMP via PRR eg.TLR4 over activates innate immune system which in turn inhibits the mitochondrial respiration and decreases the mitochondrial genome. Nuclear genome overpowers mitochondrial genome which results in the loss of the endosymbiotic relation between them, produces Warburg effect and the bacterial /mitochondrial invasion is successfully defeated. By Warburg effect, the eukaryotic host cell now returned to its original billion year old primitive form i.e. it became archaea like. This dedifferentiated state switching can be seen as the cells local survival strategy in response to injuries as the cells are now archaea like which has the ability to live in harsh environments. But returning to their primitive forms leads to disorder and ends in global collapse of the organ systems and organism which requires order in terms of differentiation which is maintained by the mitochondrial system in the eukaryotic cell and across the cells by intercellular mitochondrial transfer. Death of the organism may be due to the immortality pathway chosen by the cells locally. 2) Successful bacterial /mitochondrial invasion of the eukaryotic host will increase the mitochondrial genome and overpower the nuclear genome which may trigger apoptosis by degrading the nuclear genome and expelling it. 3) Partially successful invasion may result in the formation of cellular memory by increase in both OXPHOS and glycolysis. I propose that the treatment in septic shock should aim at activation of mitochondrial respiration thereby decreasing the aerobic glycolysis and changing the cell to its normal adult dynamic differentiation phenotype i.e all the drugs should be used as differentiation therapy. Adrenergic blockers and ascorbic acid may be the main treatment options, which are already used by some research groups. Abbrevations :, Oxidative phosphorylation (OXPHOS),Pathogen associated molecular pattern (PAMP), Danger associated molecular pattern(DAMP),Pattern recognition receptor(PRR),Toll like receptor (TLR).

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