Medical management of victims contaminated with radionuclides after a “dirty bomb” attack

Abstract A wide spectrum of scenarios may lead to radiation incidents and the liberation of radioactive material. In the case of a terrorist attack by a “dirty bomb”, there is a risk of mechanical and thermal trauma, external irradiation, superficial contamination and incorporation of radioactive material. The first treatment priority must be given to the care of trauma patients with life-threatening injuries, as the health effects of radiation occur with latency. Radionuclide incorporation will lead to a longer-lasting irradiation from inside the body, associated with a higher risk of stochastic radiation effects (e.g., occurrence of tumors) in the long run. It must be expected that victims with potentially incorporated radionuclides will far outnumber trauma patients. The elimination of radionuclides can be enhanced by the administration of decorporation agents such as (Ca) Diethylenetriaminepentaacetic acid (DTPA) or Prussian blue, reducing the radiological burden of the body. There is still no consensus whether decorporation treatment should be started immediately based only on a suspicion of radionuclide incorporation (“urgent approach”) or if the results of internal dosimetry confirming the necessity of a treatment should be awaited, accepting the delay caused by the measurements and computations (“precautionary approach”). As the therapeutic effectiveness may be substantially decreased if treatment initiation is delayed only by several days, depending on the radionuclide, the physicochemical properties of the compounds involved and the route of absorption, we favor an “urgent approach” from a medical point of view. In doubt, it seems justified to treat victims by precaution, as the adverse effects of the medication seem minimal. However, in the case of a high number of victims, an “urgent treatment approach” may require a large number of daily doses of antidotes, and therefore, adequate investments in preparedness and antidote stockpiling are necessary

Pharmacological treatment of inhalation injury after nuclear or radiological incidents: The Chinese and German approach

Abstract Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and, if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents (e.g., nitrites, dimethylaminophenol) or hydroxocobalamin (Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca (DTPA) or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca (DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany

A comparison of thyroidal protection by stable iodine or perchlorate in the case of acute or prolonged radioiodine exposure

In the case of a nuclear power plant accident, repetitive/prolonged radioiodine release may occur. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of non-radioactive iodine may protect the thyroid by inhibiting radioiodine uptake into the gland (iodine blockade). Protection is based on a competition at the active carrier site in the cellular membrane and the Wolff-Chaikoff effect, the latter being, however, only transient (24-48 h). Perchlorate may alternatively provide protection by a carrier competition mechanism only. Perchlorate has, however, a stronger affinity to the carrier than iodide. Based on an established biokinetic-dosimetric model developed to study iodine blockade, and after its extension to describe perchlorate pharmacokinetics and the inhibition of iodine transport through the carrier, we computed the protective efficacies that can be achieved by stable iodine or perchlorate in the case of an acute or prolonged radioiodine exposure. In the case of acute radioiodine exposure, perchlorate is less potent than stable iodine considering its E

MicroRNA Expression for Early Prediction of Late Occurring Hematologic Acute Radiation Syndrome in Baboons.

For effective medical management of radiation-exposed persons after a radiological/nuclear event, blood-based screening measures in the first few days that could predict hematologic acute radiation syndrome (HARS) are needed. For HARS severity prediction, we used microRNA (miRNA) expression changes measured on days one and two after irradiation in a baboon model. Eighteen baboons underwent different patterns of partial or total body irradiation, corresponding to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts (BCC) the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS. In a two Stage study design we screened 667 miRNAs using a quantitative real-time polymerase chain reaction (qRT-PCR) platform. In Stage II we validated candidates where miRNAs had to show a similar regulation (up- or down-regulated) and a significant 2-fold miRNA expression difference over H0. Seventy-two candidate miRNAs (42 for H1-2 and 30 for H2-3) were forwarded for validation. Forty-two of the H1-2 miRNA candidates from the screening phase entered the validation step and 20 of them showed a statistically significant 2-4 fold up-regulation relative to the unexposed reference (H0). Fifteen of the 30 H2-3 miRNAs were validated in Stage II. All miRNAs appeared 2-3 fold down-regulated over H0 and allowed an almost complete separation of HARS categories; the strongest candidate, miR-342-3p, showed a sustained and 10-fold down-regulation on both days 1 and 2. In summary, our data support the medical decision making of the HARS even within the first two days after exposure where diagnostic tools for early medical decision are required but so far missing. The miRNA species identified and in particular miR-342-3p add to the previously identified mRNAs and complete the portfolio of identified mRNA and miRNA transcripts for HARS prediction and medical management

Decline of mean fpc values in PBL of ∼49 Gy PBI γ-exposed minipigs.

<p>Mean fpc values ± SD are shown. While the study comprises only 3 time points the shape of the obtained function is consistent with that known for DNA repair after <i>in vitro</i> irradiation of minipig cells <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087458#pone.0087458-Moroni2" target="_blank">[9]</a>.</p

Frequency of pan-γH2AX labeled PBL nuclei in minipig blood.

<p>(A) Image of γH2AX (green) and 53BP1 (red) stained PBL showing a pan-γH2AX-positive nucleus (arrow) with numerous 53BP1 (red) foci. DNA is stained in blue (DAPI). (B) Percentage of minipig PBL carrying a pan-γH2AX signal (compare also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087458#pone-0087458-g001" target="_blank">Fig. 1B</a>). Mean and SD of samples from 13 minipigs is shown.</p

Images showing foci of γH2AX, 53BP1 and MRE11 DSB-marking proteins in nuclei of peripheral blood lymphocytes of minipigs.

<p>(<b>A–C</b>) Images of minipig PBL immunostained for γH2AX (green), 53BP1 (red) and nuclei (DNA, blue; DAPI). (<b>A</b>) Control cells without IR exposure and DNA damage foci. (<b>B</b>) Minipig PBL 4 h post 49 Gy irradiation revealing fluorescent foci of γH2AX and 53BP1 marking DSBs. Foci usually contain variable amounts of both DSB markers leading to reddish – greenish colored foci due to color overlap (see insets in C,D). A cell with pan-γH2AX staining shows heavy overall green labeling (arrow). (<b>C</b>) PBL nuclei obtained 4 h post IR. A cell with 8 foci is seen in the image center (arrow). Inset: fluorescence intensity profiles across 5 foci in 3 PBL nuclei revealing colocalization of green γH2AX and red 53BP1 fluorescence intensity peaks. (<b>D</b>) PBLs of a 4 h sample showing colocalization of the DNA repair protein MRE11 (red) and γH2AX (green) at DNA damage foci, those appear whitish due to color overlap. The inset shows fluorescence intensity profiles across 4 foci in 2 PBL nuclei revealing colocalization of green γH2AX and red MRE11 fluorescence intensity peaks. Magnification 630× in the original micrographs.</p

Antibodies, dilutions and sources.

<p>Antibodies, dilutions and sources.</p