• Iron in Dense Matted Deposits in Diabetes and SARS-CoV-2

    From ironjustice@21:1/5 to All on Thu Jun 22 05:59:07 2023
    Here's all the iron, 'dense matted deposits ( DMD)', found also in SARS-CoV-2.

    Differences in morphology of fibrin clots induced with thrombin and ferric ions and its pathophysiological consequences
    E Pretorius 1, B Lipinski
    Heart Lung Circ. 2013 Jun;22(6):447-9. Epub 2012 Dec 7.
    PMID: 23219312 doi: 10.1016/j.hlc.2012.10.010.
    The activation of blood coagulation leads to the formation of thrombin that, in turn, converts soluble plasma fibrinogen into insoluble fibrin clot. In healthy individuals, fibrin is effectively degraded; however, in prothrombotic states, proteolysis of
    fibrin clots are often delayed or even inhibited, and is associated with altered fibrin structure. We have previously shown that in inflammatory conditions like stroke and diabetes, this fibrin forms dense matted deposits. Although there are several
    factors that modify fibrin structure and delay fibrinolysis in these conditions, no mechanism is yet known to be responsible for a persistent presence of thrombi in the coronary and/or cerebral circulations. It seems, therefore, desirable to better
    understand this phenomenon in order to improve the effectiveness of thrombolytic therapies. Here, we show that ferric ions can activate non-enzymatic blood coagulation resulting in the formation of fibrin-like dense matted deposits (DMD) demonstrable by
    electron scanning microscopy (SEM). These DMDs are similar to those found in stroke and diabetes. On the basis of these findings we can conclude that the spontaneous formation of fibrin-like dense deposits in patients' blood may be a consequence of what
    is known as iron overload. Therefore, it is possible that inactivation of unbound iron in blood by small molecular weight chelating agents may prevent thrombotic consequences of the excessive accumulation of iron in the circulation.

    Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
    "Oxidative stress plus free iron converts soluble plasma fibrinogen into abnormal fibrin clots in the form of dense matted deposits (DMD resistant to the enzymatic degradation; blood clots), leading to microthrombosis in the vascular system and the
    pulmonary microcirculation." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357498/
    SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression
    Rubens Cecchinia and Alessandra Lourenço Cecchinib,
    Med Hypotheses. 2020 Oct; 143: 110102.
    Published online 2020 Jul 13. doi: 10.1016/j.mehy.2020.110102
    PMCID: PMC7357498
    PMID: 32721799
    Since the WHO declared COVID-19 a pandemic, a great effort has been made to understand this serious disease. Thousands of studies are being devoted to understanding its epidemiology, its molecular characteristics, its mechanisms, and the clinical
    evolution of this viral infection. However, little has been published on its pathogenesis and the host response mechanisms in the progress of the disease. Therefore, we propose a hypothesis based on strong scientific documentation, associating oxidative
    stress with changes found in patients with COVID-19, such as its participation in the amplification and perpetuation of the cytokine storm, coagulopathy, and cell hypoxia. Finally, we suggest a therapeutic strategy to reduce oxidative stress using
    antioxidants, NF-κB inhibitors, Nrf2 activators, and iron complexing agents. We believe that this hypothesis can guide new studies and therapeutic strategies on this topic.
    ------------------------------------------------------------------- Non-transferrin-bound iron: a promising biomarker in iron overload disorders. Maas RP, Voets PJ, de Swart L, Swinkels DW.
    Ned Tijdschr Geneeskd. 2013;157(49):A6258.
    Radboudumc, Nijmegen.

    Iron overload disorders are common and, if left untreated, severe systemic diseases that can have both genetic and acquired causes.
    Hereditary haemochromatosis, β-thalassaemia, myelodysplastic syndromes and sickle cell disease are among the most important examples.
    Iron that is not bound to transferrin, haem or ferritin (non-transferrin-bound iron, NTBI) seems to play a key role in the pathophysiology of these disorders.
    NTBI is a heterogeneous group of potentially toxic iron complexes in plasma which are generated almost exclusively under pathological conditions.
    Cellular uptake of NTBI contributes to its toxicity and is mediated by several organ-specific transporters and receptors.
    NTBI-induced toxicity is the result of oxidative damage to various macromolecules by reactive oxygen species (ROS).
    In the near future, we hypothesize that NTBI will have important implications for both diagnosis and treatment of iron overload disorders.
    However, before NTBI can be applied to patient care, the currently available assays need further clinical and analytical validation.



    "RESULTS: NTBI (non-transferrin-bound iron ) was commonly present in
    diabetes: 59% in newly diagnosed diabetes and 92% in advanced diabetes"

    Common presence of non-transferrin-bound iron among patients with type
    2 diabetes.
    Diabetes Care. 2006 May;29(5):1090-5.
    Lee DH, Liu DY, Jacobs DR Jr, Shin HR, Song K, Lee IK, Kim B, Hider RC. Department of Preventive Medicine, School of Medicine, Kyungpook
    University, 101 Dongin-dong, Jung-gu, Daegu, Korea 700-422.

    OBJECTIVE: Recently, we reported increased cardiovascular disease
    mortality among supplemental vitamin C users with type 2 diabetes in a prospective cohort study. Because vitamin C may cause oxidative stress
    in the presence of redox active iron, we hypothesized that non-transferrin-bound iron (NTBI), a form of iron susceptible to redox activity, may be present in patients with type 2 diabetes. RESEARCH
    DESIGN AND METHODS: We measured serum NTBI levels using
    high-performance liquid chromatography in 48 patients with known
    diabetes (at least 5 years duration since diagnosis), 49 patients with
    newly diagnosed diabetes, and 47 healthy control subjects (frequency
    matched on age and sex). RESULTS: NTBI was commonly present in
    diabetes: 59% in newly diagnosed diabetes and 92% in advanced diabetes.
    Mean NTBI values varied significantly between the three groups, with
    the highest values being observed in patients with known diabetes and
    the lowest in the control subjects (0.62 +/- 0.43 vs. 0.24 +/- 0.29 vs.
    0.04 +/- 0.13 mumol/l Fe). Serum total iron or percent transferrin
    saturation were very similar among the three groups, yet NTBI was
    strongly associated with serum total iron (r = 0.74, P < 0.01) and
    percent transferrin saturation (r = 0.70, P < 0.01) among the patients
    with known diabetes. CONCLUSIONS: Consistent with our hypothesis, these
    data demonstrate the common existence of NTBI in type 2 diabetic
    patients with a strong gradient with severity. Prospective cohort
    studies are required to clarify the clinical relevance of increased
    NTBI levels.

    PMID: 16644642

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