The Glyoxalase System and Methylglyoxal-Derived Carbonyl Stress in Sepsis: Glycotoxic Aspects of Sepsis Pathophysiology

Schmoch, Thomas; Uhle, Florian; Siegler, Benedikt Hermann; Fleming, Thomas; Morgenstern, Jakob; Nawroth, Peter P.; Weigand, Markus A.; Brenner, Thorsten

doi:10.3390/ijms18030657

Cited by 27 publications

(22 citation statements)

References 166 publications

(214 reference statements)

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“…In later stages oxidation of fatty acids may also be impaired, as reflected in elevated serum levels of lipoproteins, free fatty acids and triglycerides. Glycolysis is favored over oxidative phosphorylation despite adequate oxygen availability ("aerobic glycolysis", sometimes called the Warburg Effect) [206][207][208]. There is accelerated catabolism of skeletal muscle and perhaps smooth muscle as well [209].…”

Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 -supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

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Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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“…Анализировалась роль различных иммунных клеток, про-и противовоспалительных цитокинов и т. д. [22,29,36,43]. Цитокины являются важнейшими медиаторами, которые регулируют воспалительные реакции.…”

Section: Abstract: Sepsis Apoptosis Immunosupression Neutrophilsunclassified

Disturbance of an Apoptosis of Neutrophils at a Sepsis

Shen

Гуан

Ду

et al. 2018

Russian Journal of Infection and Immunity

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The sepsis represents life-endangering disturbances of functions of the internals caused by a dizregulyation of a macroorganism to the infectious agent and is difficult interaction of pro-inflammatory and antiinflammatory processes that not seldom defines the fate of patients. The predetermining factor of a sepsis is the originator. The immunosupression caused by the originator promotes generalization of an infection, and the intensive bacteriemia caused by generalization leads to the accruing endotoxinemia that aggravates immunosupression even more and leads finally to systemic inflammatory reaction — the main and most dangerous implication of a sepsis. The syndrome of systemic inflammation with uncontrollable emission of cytokines is the cornerstone of a sepsis. The pathophysiology of a sepsis begins with impassioned inflammatory reaction which can last several days, and then passes into more lingering immunosupressivny period where the outcome depends on the immune system of the patient. Cellular apoptosis is one of leaders in sepsis immunosupression development. In article mechanisms of disturbance of an apoptosis of neutrophils are described that, undoubtedly, affects weighting of a current of a sepsis and as a result, a failure. Migration of neutrophils under natural conditions includes four various phases which during a sepsis are broken. The mechanisms worsening migration of neutrophils, contributing to the development of a sepsis were investigated in numerous scientific works. Authors of Peking University offered schemes of a way of disturbance of an apoptosis of neutrophils and migration of neutrophils at a sepsis. Despite the extensive accumulated experience on studying of a pathogenesis of septic states, there are no effective and specific remedies of fight from a sepsis now. Perhaps, by prevention of disturbance of the programmed death of a cell the cytokines developed anti-apoptotic, caspase inhibitors will be.

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“…( 2 – 4 ) Since sepsis is caused by a viral, fungal or bacterial infection, the early phase of sepsis is characterized by a massive formation of reactive oxygen and nitrogen species such as superoxide and nitric oxide. ( 5 – 7 ) Peroxynitrite, which is produced from the combination of superoxide and nitric oxide, is also an important reactive molecule. ( 5 – 7 )…”

Section: Introductionmentioning

confidence: 99%

Increased oxidative stress and renal injury in patients with sepsis

Yamaguchi

Nagase

Yamamoto

et al. 2018

J. Clin. Biochem. Nutr.

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Sepsis remains one of the leading causes of death in intensive care units. The early phase of sepsis is characterized by a massive formation of reactive oxygen and nitrogen species such as superoxide and nitric oxide. However, few comprehensive studies on plasma antioxidants have been reported. Increased oxidative stress was confirmed in sepsis patients (n = 18) at the time of hospitalization by a significant decrease in plasma ascorbic acid and a significant increase in the percentage of oxidized form of coenzyme Q10 in total coenzyme Q10 compared to age-matched healthy controls (n = 62). Tissue oxidative damage in patients was suggested by a significant decrease in polyunsaturated fatty acid contents and a significant increase in oleic acid contents in total free fatty acids. Thus, it is reasonable that plasma uric acid (end product of purines) would be significantly elevated. However, uric acid levels were continuously decreased during hospitalization for 7 days, indicating a continuous formation of peroxynitrite. A greater decrease in free cholesterol (FC) compared to cholesterol esters (CE) was observed. Thus, the FC/CE ratio significantly increased, suggesting deficiency of lecithin-cholesterol acyltransferase secreted from the liver. Plasma levels of prosaposin, a coenzyme Q10 binding protein, significantly decreased as compared to healthy controls. This may be correlated with renal injury in sepsis patients, since the kidney is thought to be a major secretor of prosaposin.

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The Glyoxalase System and Methylglyoxal-Derived Carbonyl Stress in Sepsis: Glycotoxic Aspects of Sepsis Pathophysiology

Cited by 27 publications

References 166 publications

Surviving sepsis campaign: research priorities for sepsis and septic shock

Surviving sepsis campaign: research priorities for sepsis and septic shock

Disturbance of an Apoptosis of Neutrophils at a Sepsis

Increased oxidative stress and renal injury in patients with sepsis

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