Detection of DNA in the Plasma of Septic Patients

Martins, Gisele; Kawamura, Marcia Tie; Carvalho, Maria da Glória da Costa

doi:10.1111/j.1749-6632.2000.tb06603.x

Cited by 38 publications

(30 citation statements)

References 16 publications

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“…Healthy individuals typically display very low levels of cf-DNA in circulation. In sepsis enhanced apoptosis [19] and cell necrosis [20] result in elevated cf-DNA levels [21]. A recent study by Dwivedi et al showed a very high discriminative capability of cf-DNA to predict mortality among ICU patients with severe sepsis [14].…”

Section: Discussionmentioning

confidence: 99%

Impact of Intravenous Ascorbic Acid Infusion on Novel Biomarkers in Patients with Severe Sepsis

Natarajan¹

2014

J Pulm Respir Med

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Objective: Severe sepsis is a leading cause of mortality and morbidity in the critically ill with no reliably effective treatments. The goal of this study was to determine whether intravenous ascorbic acid impacted novel biomarkers in sepsis.Methods: This is a retrospective study of a phase I, randomized, double-blinded, placebo controlled safety trial of intravenous ascorbic acid in severe sepsis. In the safety trial, 24 patients were randomized to receive full ICU standard of care support plus intravenous ascorbic acid (50 or 200 mg/kg/24h) for 4 days or placebo. Novel biomarkers of sepsis such as circulating cell free DNA (cf-DNA), mitochondrial DNA (mtDNA), endogenous antimicrobial proteins (alpha-4-defensin [α4D] and bactericidal permeability interacting protein [BPI]) and the red cell distribution width (RDW) were measured.Results: Cf-DNA values were higher in non-survivors at baseline and remained elevated for 96 hours. MtDNA levels increased in the placebo group, but declined in the treatment groups without reaching statistical significance. RDW increased significantly only in the placebo group, while expression of the antimicrobial proteins increased significantly only in the treatment groups. Conclusion:Ascorbic acid infusion may improve sepsis outcomes by reducing cf-and mtDNA levels while augmenting endogenous antimicrobial proteins and preserving RDW.

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Section: Discussionmentioning

confidence: 99%

Impact of Intravenous Ascorbic Acid Infusion on Novel Biomarkers in Patients with Severe Sepsis

Natarajan¹

2014

J Pulm Respir Med

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“…23,31,33 This may increase the ability to measure certain biomarkers of NETs in plasma. Indeed, DNA 75 and nucleosomes 76 are elevated in septic patients, and cell-free DNA levels were a better predictor of progression to sepsis after traumatic injury than interleukin-6 or C-reactive protein, markers of inflammation. 77 MPO-DNA complexes are elevated specifically during active disease in patients with small-vessel 25 when their thrombotic risk is the highest.…”

Section: Nets In Human Thrombosismentioning

confidence: 99%

Thrombosis: tangled up in NETs

Martinod

Wagner

2014

Blood

696

622

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The contributions by blood cells to pathological venous thrombosis were only recently appreciated. Both platelets and neutrophils are now recognized as crucial for thrombus initiation and progression. Here we review the most recent findings regarding the role of neutrophil extracellular traps (NETs) in thrombosis. We describe the biological process of NET formation (NETosis) and how the extracellular release of DNA and protein components of NETs, such as histones and serine proteases, contributes to coagulation and platelet aggregation. Animal models have unveiled conditions in which NETs form and their relation to thrombogenesis. Genetically engineered mice enable further elucidation of the pathways contributing to NETosis at the molecular level. Peptidylarginine deiminase 4, an enzyme that mediates chromatin decondensation, was identified to regulate both NETosis and pathological thrombosis. A growing body of evidence reveals that NETs also form in human thrombosis and that NET biomarkers in plasma reflect disease activity. The cell biology of NETosis is still being actively characterized and may provide novel insights for the design of specific inhibitory therapeutics. After a review of the relevant literature, we propose new ways to approach thrombolysis and suggest potential prophylactic and therapeutic agents for thrombosis.

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“…Since its discovery, cfDNA has been found to be increased in a variety of neoplastic and non-neoplastic diseases of humans, including myocardial infarction (Chang et al 2002), rheumatoid arthritis (Zhong et al 2007), severe viral infections (Ha et al 2011), stroke , sepsis (Martins et al 2000;Rhodes et al 2006) and severe trauma (Lo et al 2000;Lam et al 2003;Macher et al 2012). In all these diseases, the cfDNA concentrations have correlated with disease severity and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Investigation of cell-free DNA in canine plasma and its relation to disease

Burnett

Cave

Gedye

et al. 2016

Veterinary Quarterly

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Background: DNA is released from dying cells during apoptosis and necrosis. This cell-free DNA (cfDNA) diffuses into the plasma where it can be measured. In humans, an increase in cfDNA correlates with disease severity and prognosis. Objective: It was hypothesized that when DNA in canine plasma was measured by emission fluorometry without prior DNA extraction, the concentration of cfDNA would increase with disease severity. Animals: The diseased population consisted of 97 client-owned dogs. The clinically normal population consisted of nine client-owned dogs presenting for 'wellness screens', and 15 colony-owned Harrier Hounds. Methods: Plasma cfDNA was measured by fluorometry without prior DNA extraction. The effects of ex vivo storage conditions were evaluated in plasma from two clinically normal dogs. In all other dogs, plasma was separated within two hours of collection. The association between the cfDNA concentration in hospitalized dogs and a variety of clinical, clinicopathological and outcome variables was tested. Results: The concentration of cfDNA was reliably measured when plasma was separated within two hours of blood collection. The diseased dogs had significantly higher cfDNA than clinically normal dogs (P < 0.001), and the more severe the disease, the higher the cfDNA when severity was categorized according to the American Society of Anesthesiologists (ASA) status (P < 0.001). Dogs that did not survive to discharge had significantly higher cfDNA concentrations than survivors (P D 0.02). Conclusions/Clinical Importance: The concentration of cfDNA in the plasma of diseased dogs is associated with disease severity and prognosis. Measurement of canine cfDNA could be a useful non-specific disease indicator and prognostic tool.

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Detection of DNA in the Plasma of Septic Patients

Cited by 38 publications

References 16 publications

Impact of Intravenous Ascorbic Acid Infusion on Novel Biomarkers in Patients with Severe Sepsis

Impact of Intravenous Ascorbic Acid Infusion on Novel Biomarkers in Patients with Severe Sepsis

Thrombosis: tangled up in NETs

Investigation of cell-free DNA in canine plasma and its relation to disease

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