Electron Paramagnetic Resonance Analysis of Transferrin-Bound Iron in Animal Models of Blunt Trauma

Gorbunov, Nikolai V.; Nath, Jayasree; Parker, J.D.; Zaucha, Gary M.

doi:10.1097/01.ta.0000043922.40376.38

Cited by 9 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This iron dysregulation can be initiated by a multitude of factors that cause cell death, which will release free iron into the bloodstream, whence it can be disseminated throughout the body (Kell & Pretorius, ). Such factors include mechanical damage [including trauma (Gorbunov et al ., , , ; Zhang et al ., ) and dysbiosis], nutritional stress (Schaffer, , ), pharmacological stress (Pirmohamed et al ., ), oxidative stress (Crichton, ; Kerley et al ., ) and others (Nanba et al ., ), many of which also involve the production of stress hormones.…”

Section: Step 0: Iron Dysregulation Caused By Externally Induced Strementioning

confidence: 99%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

View full text Add to dashboard Cite

Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.

show abstract

Section: Step 0: Iron Dysregulation Caused By Externally Induced Strementioning

confidence: 99%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

View full text Add to dashboard Cite

show abstract

“…Maryland, USA undertook a series of studies to define the role of iron and iron-transferrin in blast injury, as part of a broader program looking at oxidative stress and free radical damage precipitated by blast injury. It has been demonstrated that iron is sequestrated into the tissues as a result of trauma, as mentioned above, and of further relevance this has been demonstrated in blast injury (32). Gorbunov showed that different models of injury, including exposure to blast overpressure in a rat, produced a reduction in the amount of irontransferrin in the blood, and that this reduction was inversely correlated with the severity of injury (33).…”

Section: Nikolai Gorbunov and His Colleagues At The Walter Reed Instimentioning

confidence: 86%

The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population

Lumley

Osborn

Mellor

et al. 2018

Journal of Critical Care

View full text Add to dashboard Cite

show abstract

“…Phase I of the study design was focused on pro-inflammatory alterations overpressure peak Fig. 1 (20). Accidents of lethal outcome (mortality rate was~25%) usually developed during the first 15 min of post-exposure and were excluded from further analyses.…”

Section: Treatment Ofanimalsmentioning

confidence: 99%

“…The facilities are fully accredited by the Association for Assessment and Accreditation ofLaboratory Animal Care International. EPR analysis Assessment ofblood [Fe+]TRF was conducted with lowtemperature EPR spectroscopy as described previously (20). Briefly, 0.6 ml of blood was collected in 1 cc syringes free from latex and silicone oil (Henke-Sass, Wolf; Gmbh, Germany) to make blood samples of constant volume and geometrical profile.…”

Section: Treatment Ofanimalsmentioning

confidence: 99%

See 1 more Smart Citation

Pro-Inflammatory Alterations and Status of Blood Plasma Iron in a Model of Blast-Induced Lung Trauma

Gorbunov

McFaul

Januszkiewicz

et al. 2005

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Impact of blast shock waves (SW) with the body wall produces blast lung injuries characterized by bilateral traumatic hemorrhages. Such injuries often have no external signs, are difficult to diagnose, and therefore, are frequently underestimated. Predictive assessment of acute respiratory distress syndrome outcome in SW-related accidents should be based on experimental data from appropriate animal models. Blood plasma transferrin is a major carrier of blood iron essential for proliferative "emergency" response of hematopoietic and immune systems as well as injured tissue in major trauma. Iron-transferrin complexes ([Fe 3+]TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use ofEPR techniques in combination with assays for pro-inflammatory cytokines and granulocytes in the peripheral blood and BAL would reveal a pattern of systemic sequestration of [Fe 3+]TRF that could be useful for development of biomarkers of the systemic inflammatory response to lung injury. With this goal we (i) analyzed time-dependent dynamics of [Fe 3+]TRF in the peripheral blood of rats after impacts of SW generated in a laboratory shock-tube and (ii) assayed the fluctuation of granulocyte (PMN) counts and expression of CDllb adhesion molecules on the surface of PMNs during the first 24 h after SWinduced injury. Sham-treated animals were used as control. Exposure to sw led to a significant decrease in the amount of blood [FeJ+]TRFthat correlated with the extent oflung injury and developed gradually during the first 24 h. Thus, sequestration of [FeJ+]TRF occurred as early as 3 h post-exposure. At that time, the steady state concentration of [Fe3+]TRF in blood samples decreased from 19.7±O.6~M in controls to 7.5±1.3 11M in exposed animals. The levels of [Fe 3+]TRF remained decreased thoughout the entire study period. PMN counts increased 5-fold and 3.5-fold over controls respectively, at 3 and 6 h postexposure. These effects were accompanied by an increase in expression ofCDllb on the surface membrane ofPMNs. Extensive release of cytokines IL-l, IL-6, MCP-l, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood [Fe 3+]TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.Detonation of explosives generates blast shock waves (SW) which are usually characterized by (i) amplitude of blast overpressure, (ii) frequency of sound, and (iii) kinetic energy of striking force, and are considered to be major factors that produce the blastinjured casualty (l -4). A pattern of striking injuries ranges from displacement and rupture of bone and organs to amputations oflimbs and can be assessed by the existing biomechanical models for high-velocity, low-mass impacts (l, 5-6). The effects produced by SW-generated sound and SW-generated overpressure are more complex and remain beyond the framework of predictive biomechanical models. These damaging effects of...

show abstract

Electron Paramagnetic Resonance Analysis of Transferrin-Bound Iron in Animal Models of Blunt Trauma

Cited by 9 publications

References 29 publications

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population

Pro-Inflammatory Alterations and Status of Blood Plasma Iron in a Model of Blast-Induced Lung Trauma

Contact Info

Product

Resources

About