Succimer chelation does not produce lasting reductions of blood lead levels in a rodent model of retained lead fragments.

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNaEDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments.

Oxidative damage in metal fragment-embedded Sprague-Dawley rat gastrocnemius muscle.

Injuries suffered in armed conflicts often result in wounds with embedded metal fragments. Standard surgical guidance has been to leave fragments in place except under certain circumstances; meaning that individuals may carry these retained fragments for their lifetime. Because of advancements in weapon design and the use of improvised explosive devices, the list of metals that could be found in a wound is extensive.

Serum Indicators of Oxidative Damage from Embedded Metal Fragments in a Rat Model.

Injuries suffered in armed conflicts often result in embedded metal fragments. Standard surgical guidance recommends leaving embedded fragments in place except under certain circumstances in an attempt to avoid the potential morbidity that extensive surgery often brings. However, technological advances in weapon systems and insurgent use of improvised explosive devices now mean that practically any metal can be found in these types of wounds.

Protein Expression in the Gastrocnemius Muscle of a Rodent Shrapnel-Injury Model.

With shrapnel injuries, the metal fragment is usually left in place to reduce the risk of morbidity extensive surgery might bring. This means the individual may retain those metals for the remainder of their life. Often the long-term health effects of the embedded metal are not known, especially with respect to protein damage and perturbations of muscle repair pathways.

Nutraceuticals as Potential Radionuclide Decorporation Agents.

Exposure of individuals to radioactive material as a result of ingestion of contaminated food and water is an increasing public health concern. Unfortunately, there are limited treatment modalities for dealing with these types of potentially toxic exposures. Recent research suggests that many plant-based nutraceuticals may possess metal-binding properties.

Celebrating 60 Years of Accomplishments of the Armed Forces Radiobiology Research Institute1.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe.

Effect of embedded metal fragments on urinary metal levels and kidney biomarkers in the Sprague-Dawley rat.

Background: Wounds with embedded metal fragments are an unfortunate consequence of armed conflicts. In many cases the exact identity of the metal(s) and their long-term health effects, especially on the kidney, are not known.

Aim Of Study: The aim of this study was to quantitate the urinary levels of metals solubilized from surgically implanted metal pellets and to assess the effect of these metals on the kidney using a battery of biomarker assays.

Brain region- and metal-specific effects of embedded metals in a shrapnel wound model in the rat.

The health effects of prolonged exposure to embedded metal fragments, such as those found in shrapnel wounds sustained by an increasing number of military personnel, are not well known. As part of a large collaborative effort to expand this knowledge, we use an animal model of shrapnel wounds originally developed to investigate effects of embedded depleted uranium to investigate effects of military-relevant metals tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium compared to an inert control, tantalum. Rats are surgically implanted with pellets of one of the metals of interest in the gastrocnemius (leg) muscle and tracked until 1 month, 3 months, 6 months, or 12 months from the time of implant, at which point they are euthanized and multiple organs and tissue samples are collected for inspection.

Spectroscopic and Spectrometric Approaches for Assessing the Composition of Embedded Metals in Tissues.

Many medical devices contain metals that interface with the body. Additionally, embedded metal fragments from military wounds are typically not removed, to avoid the risk of morbidity associated with invasive surgery. The long-term health consequences of many of these materials are not thoroughly understood.

Effects of Incubation of Human Brain Microvascular Endothelial Cells and Astrocytes with Pyridostigmine Bromide, DEET, or Permethrin in the Absence or Presence of Metal Salts.

Gulf War Illness (GWI) is a chronic, multi-symptom illness suffered by over one-third of American military veterans who served in the Persian Gulf War between 1990 and 1991. No current single-exposure scenario accounts for all the symptoms observed in GWI, and instead may be due to a multi-exposure scenario. As a larger effort to understand how one category of multi-exposure scenarios of organic compounds such as nerve gas prophylactic pyridostigmine bromide, or insecticides/pesticides such as N,N-diethyl--toluamide (DEET) and permethrin, plus heavy metals found in inhaled dust particles (Al, Fe, Ni, Sr, DU, Co, Cu, Mn, and Zn) might play a role in neural aspects of GWI, we begin this initial study to examine the toxicity and oxidative damage markers of human brain endothelial cell and human astrocyte cell cultures in response to these compounds.

Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.

As a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military-grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation.

Hydrophobic sand is a viable method of urine collection from the rat for extracellular vesicle biomarker analysis.

Previously we have shown in rats a new method of urine collection, hydrophobic sand, to be an acceptable alternate in place of the traditional method using metabolic cages. Hydrophobic sand is non-toxic, induces similar or lower levels of stress in the rat, and does not contaminate clinical urine markers nor metal concentrations in collected samples (Hoffman et al., 2017 and 2018).

Hydrophobic Sand Versus Metabolic Cages: A Comparison of Urine Collection Methods for Rats ().

A common method for urine collection from rats requires the use of a metabolic cage, thus exposing animals to extended periods of isolation in an unfamiliar cage with a wire-mesh floor. A new method involving hydrophobic sand, a material more similar to bedding, has become available recently but has not been extensively compared with metabolic cages in regard to collection efficiency or stress. Using a within-subjects crossover design, we examined differences in stress markers, urinary markers, and urine volume of clinically healthy male Sprague-Dawley rats during 2-, 4-, and 6-h collection sessions in hydrophobic sand and metabolic cages.

Hydrophobic Sand Is a Non-Toxic Method of Urine Collection, Appropriate for Urinary Metal Analysis in the Rat.

Hydrophobic sand is a relatively new method of urine collection in the rodent, comparable to the established method using a metabolic cage. Urine samples are often used in rodent research, especially for biomarkers of health changes after internal contamination from embedded metals, such as in a model of a military shrapnel wound. However, little research has been done on the potential interference of hydrophobic sand with urine metal concentrations either by contamination from the sand particulate, or adsorption of metals from the urine.

Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat.

The potential for exposures to ionizing radiation has increased in recent years. Although advances have been made, understanding the global metabolic response as a function of both dose and exposure time is challenging considering the complexity of the responses. Herein we report our findings on the dose- and time-dependency of the urinary response to ionizing radiation in the male rat using radiation metabolomics.

Induction of rhabdomyosarcoma by embedded military-grade tungsten/nickel/cobalt not by tungsten/nickel/iron in the B6C3F1 mouse.

Continued improvements in the ballistic properties of military munitions have led to metal formulations for which little are known about the long-term health effects. Previously we have shown that a military-grade tungsten alloy comprised of tungsten, nickel, and cobalt, when embedded into the leg muscle of F344 rats to simulate a fragment wound, induces highly aggressive metastatic rhabdomyosarcomas. An important follow-up when assessing a compound's carcinogenic potential is to test it in a second rodent species.

Chapter 4 embedded metal fragments.

The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to embedded fragment wounds containing metal and metal mixtures whose long-term toxicologic and carcinogenic properties are not as yet known. Advances in medical care have greatly increased the survival from these types of injuries. Standard surgical guidelines suggest leaving embedded fragments in place, thus individuals may carry these retained metal fragments for the rest of their lives.

Genotoxic changes to rodent cells exposed in vitro to tungsten, nickel, cobalt and iron.

Tungsten-based materials have been proposed as replacements for depleted uranium in armor-penetrating munitions and for lead in small-arms ammunition. A recent report demonstrated that a military-grade composition of tungsten, nickel, and cobalt induced a highly-aggressive, metastatic rhabdomyosarcoma when implanted into the leg muscle of laboratory rats to simulate a shrapnel wound. The early genetic changes occurring in response to embedded metal fragments are not known.

Do metals that translocate to the brain exacerbate traumatic brain injury?

Metal translocation to the brain is strictly controlled and often prevented by the blood-brain barrier. For the most part, only those metals required to maintain normal function are transported into the brain where they are under tight metabolic control. From the literature, there are reports that traumatic brain injury disrupts the blood-brain barrier.

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study.

Purpose: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined.

Materials And Methods: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays.

Radiation metabolomics. 5. Identification of urinary biomarkers of ionizing radiation exposure in nonhuman primates by mass spectrometry-based metabolomics.

Mass spectrometry-based metabolomics has previously demonstrated utility for identifying biomarkers of ionizing radiation exposure in cellular, mouse and rat in vivo radiation models. To provide a valuable link from small laboratory rodents to humans, γ-radiation-induced urinary biomarkers were investigated using a nonhuman primate total-body-irradiation model. Mass spectrometry-based metabolomics approaches were applied to determine whether biomarkers could be identified, as well as the previously discovered rodent biomarkers of γ radiation.