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

Natarajan, Ramesh

doi:10.4172/2161-105x.1000214

Cited by 17 publications

(21 citation statements)

References 47 publications

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“…The same investigators showed that in vitro supplementation of human neutrophils with vitamin C attenuated phorbol ester-induced NETosis [ 75 ]. Administration of gram doses of vitamin C to septic patients over four days, however, did not appear to decrease circulating cell-free DNA levels [ 188 ], although the duration of treatment may have been too short to see a sustained effect. It should be noted that cell-free DNA is not specific for neutrophil-derived DNA, as it may also derive from necrotic tissue; however, the association of neutrophil-specific proteins or enzymes, such as myeloperoxidase, with the DNA can potentially provide an indication of its source [ 184 ].…”

Section: Vitamin C and Leukocyte Functionmentioning

confidence: 99%

Vitamin C and Immune Function

2017

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Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

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Section: Vitamin C and Leukocyte Functionmentioning

confidence: 99%

Vitamin C and Immune Function

2017

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“…Serum ccf-mtDNA levels are influenced by inflammation [20], BMI [21] and psychosocial and physical stress [22]; factors previously linked to PD progression [23,24]. Elevated plasma ccf-mtDNA levels are associated with nonresponsiveness to selective serotonin reuptake inhibitor (SSRI) treatment in major depressive disorder (MDD) [4] and vitamin C infusion has been shown to reduce plasma ccf-mtDNA levels in sepsis patients [25], suggesting that treatment may be an important cofactor in any ccf-mtDNA assessment. In CSF, ccf-mtDNA likely originates from the ependymal cells of the choroid plexus, an area not subject to neurodegeneration in either AD or PD, but which recruits leukocytes to the brain under inflammatory conditions [26].…”

mentioning

confidence: 99%

“…However, despite evidence suggesting that variable ccf-mtDNA levels could be a manifestation of treatment [25], this has not been formally tested in PD. Thus, in this study we assessed CSF ccf-mtDNA levels in a well-characterised cohort of PD subjects and controls to test the relationship between treatment and changes in ccf-mtDNA.…”

mentioning

confidence: 99%

“…However, this reduction is also influenced by the commencement, type and duration of therapeutic intervention. Elevated ccf-mtDNA was observed in MDD patients who were unresponsive to SSRI treatment [4] and reduced ccf-mtDNA is associated with vitamin C infusion in sepsis patients [25], suggesting that ccf-mtDNA levels may be an indicator of treatment response. With regard to PD medication, L-dopa crosses the blood-brain barrier and has been shown to affect mitochondrial function [45,46], increasing neuronal mtDNA copy-number [47].…”

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confidence: 99%

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Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

Lowes

Pyle

Santibanez‐Koref

et al. 2020

Mol Neurodegeneration

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Several studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer's and Parkinson's disease (PD) patients have raised the hypothesis that ccf-mtDNA could be used as a biomarker for neurodegenerative disease onset and progression. However, how a reduction of CSF ccf-mtDNA levels relates to neurodegeneration remains unclear. Many factors are likely to influence ccf-mtDNA levels, such as concomitant therapeutic treatment and comorbidities. In this study we aimed to investigate these factors, quantifying CSF ccf-mtDNA from the Parkinson's Progression Markers Initiative in 372 PD patients and 159 matched controls at two time points. We found that ccf-mtDNA levels appear significantly reduced in PD cases when compared to matched controls and are associated with cognitive impairment. However, our data indicate that this reduction in ccf-mtDNA is also associated with the commencement, type and duration of treatment. Additionally, we found that ccf-mtDNA levels are associated with comorbidities such as depression and insomnia, however this was only significant if measured in the absence of treatment. We conclude that in PD, similar to reports in HIV and sepsis, comorbidities and treatment can both influence ccf-mtDNA homeostasis, raising the possibility that ccf-mtDNA may be useful as a biomarker for treatment response or the development of secondary phenotypes. Given that, clinically, PD manifests often decades after neurodegeneration begins, predicting who will develop disease is important. Also, identifying patients who will respond to existing treatments or develop secondary phenotypes will have increased clinical importance as PD incidence rises.

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“…In this review we will focus on the changes of RDW in sepsis and septic shock. This easy to obtain tool has become the area of interest for researchers in many disorders [1][2][3], in terms of mortality, most authors considering it an independent prognosis factor [4,5] or as a part of possible scoring systems [6][7][8], progression to more severe conditions [9, 10] and therapeutic response [11,12].…”

Section: Introductionmentioning

confidence: 99%

The Clinical Value of Red Blood Cell Distribution Width as a Prognosis Factor and Severity Marker in Sepsis and Septic Shock

Moisa

Negoiță

Corneci

2019

Central European Journal of Clinical Research

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Red blood cell distribution width (RDW) is a hematological parameter usually measured with every complete blood count. Its place in daily practice is mainly in the differential diagnosis of anemia, but nowadays, researchers are focused on different approaches for the erythrocyte’s changes in function and morphology.Sepsis and its most advanced form, septic shock, induces profound disturbances into organ system’s function and morphology. The red blood cells physiology and structure are directly and indirectly altered by these im balances produced in sepsis. RDW was studied in many diseases, like acute heart failure, acute stroke, inflammatory bowel diseases, chronic lung diseases and cancer, but also in sepsis. Its changes are seen to be mainly associated with prognosis. Higher values of RDW are correlated with mortality and severity of illnes in septic and all-cause critically ill patients. RDW was studied also as an independent variable in different predictive scores and some studies suggest it should be introduced in the scores use on a daily basis in critical care settings and emergency departments.In this review we will focus on how RDW was associated with mortality and severity of illness in the recent literature, as an independent prognosis factor and as a component part in different predictive and severity scores.

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

Cited by 17 publications

References 47 publications

Vitamin C and Immune Function

Vitamin C and Immune Function

Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

The Clinical Value of Red Blood Cell Distribution Width as a Prognosis Factor and Severity Marker in Sepsis and Septic Shock

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