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In the current international situation, there is the possibility of nuclear war and nuclear terrorism. The nuclear and radiological emergency in the event of an accident should be enhanced. The World Health Organization (WHO) issued a publication on January 27, 2023, updating the list of drugs recommended for stockpiling in response to radiation and nuclear emergencies, which was the first update since 2007. The list of recommended drug stocks in the publication includes drugs to prevent or reduce the effects of radiation, as well as drugs used to treat injuries after exposure. Based on the list of drugs, this article reviews the emergency response to nuclear and radiological accidents, the general situation of emergency drug stockpiles, drug reserves in some countries, and current considerations, with a view to providing references for emergency medical rescue in nuclear and radiological accidents in China.
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As is known, the nuclear accident resulting from the explosion of a nuclear weapon or the release of nuclear material could cause acute radiation syndrome within a short time. The study had found that the dose of > 0.7 Gy radiation on human body can result in persistent myelosuppression, a kind of acute radiation syndrome, leading to pancytopenia, bleeding, infection and other injuries. Several evidences also have shown that hematopoietic stem cell is conducive to repair hematopoietic injury in bone marrow, improve hematopoietic microenvironment and promote hematopoietic reconstruction. Therefore, hematopoietic stem cell transplantation is widely considered as the main treatment of the bone marrow acute radiation syndrome. However, before a surgery of hematopoietic stem cell transplantation, it still needs more research on donor selection, formulation of preconditioning and prevention of complications such as graft-versus-host disease. This paper mainly summarizes the application and research progress of hematopoietic stem cell transplantation in treating radiation injury.
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Acute radiation syndrome (ARS) is a systemic disease caused by radiation exposure, which mainly includes damage to the hematopoietic system and intestinal tract. At present, the application of cytokines to repair hematopoiesis and restore the integrity of the intestinal mucosa is one of the clinical treatment. Cytokines related to hematopoietic system repair include granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), thrombopoietin and interleukin-12 (IL-12). Meanwhile, the cytokines related to intestinal mucosal repair mainly are epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). The application of cytokines can improve the survival of ARS, however, there are still some obstacles such as easily degraded and inactivated by enzymes, short half-life and high toxicity in vivo. In order to overcome these issues, there are numerous developing effective delivery systems were carried out, including nanoparticles, hydrogels and microspheres. All of the delivery systems implied obvious advantages in protecting cytokines from degradation, prolonging half-life and reducing system toxicity. In this paper, the research progress of the functions, mechanism and delivery systems of cytokines in ARS treatment in recent years was reviewed.
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BACKGROUND: In Korea, there were repeated radiation exposure accidents among non-destructive testing workers. Most of the cases involved local injury, such as radiation burns or hematopoietic cancer. Herein, we report a case of acute radiation syndrome caused by short periods of high exposure to ionizing radiation. CASE PRESENTATION: In January 2017, Korea Information System on Occupational Exposure (KISOE) found that a 31-year-old man who had worked in a non-destructive testing company had been overexposed to radiation. The patient complained of symptoms of anorexia, general weakness, prostration, and mild dizziness for several days. He was anemic. The venous injection areas had bruises and bleeding tendency. Blood and bone marrow testing showed pancytopenia and the patient was diagnosed with acute radiation syndrome (white blood cells: 1400/cubic mm, hemoglobin: 7.1 g/dL, platelets: 14000/cubic mm). He was immediately prohibited from working and blood transfusion was commenced. The patient’s radiation exposure dose was over 1.4 Gy (95% confidence limits: 1.1–1.6) in lymphocyte depletion kinetics. It was revealed that the patient had been performing non-destructive tests without radiation shielding when working in high places of the large pipe surface. CONCLUSIONS: Exposure prevention is clearly possible in radiation-exposed workers. Strict legal amendments to safety procedures are essential to prevent repeated radiation exposure accidents.
Subject(s)
Adult , Humans , Acute Radiation Syndrome , Anorexia , Blood Cells , Blood Transfusion , Bone Marrow , Burns , Contusions , Dizziness , Hemorrhage , Information Systems , Kinetics , Korea , Lymphocyte Depletion , Occupational Exposure , Pancytopenia , Radiation Exposure , Radiation, IonizingABSTRACT
Objective To understand the radiation protection effect of pre-irradiation administrations of nilestriol on the mice with bone marrow type of acute radiation syndrome after irradiation with 60Co γ-rays,along with its mechanisms for improvement of hematopoiesis.Methods The nilestriol administration protocols were prepared by analysis of peripheral blood cell counts and survival rate experiment on mice.The mechanisms by which the pre-irradiation twice administrations improved the post-irradiation recovery of bone marrow hematopoiesis were studied by the analysis of the surface marker of bone marrow hematopoietic stem/progenitor cells of mice and by the inspection of hematopoietic progenitor cell colony and by using histopathological assessment of bone marrow.Results Pre-irradiation administration of nilestriol at two-or three-day intervals had been shown to increase survival rates up to 100％ in mice exposed to 9.0 Gy γ-rays,which was superior to a single administration (20％,x2 =21.66,21.66,P ＜0.05).The pre-irradiation administration both at one-day or two-day intervals were capable of improving the recovery of peripheral blood counts,including white blood cell (WBC),red blood cell (RBC),and platelet in mice exposed to 6.5 Gy (F =21.33,100.9,49.34,19.19,P ＜ 0.05),showing the better effects than a single administration (F =17.11,63.38,21.89,14.37,P ＜ 0.05).The two-day-interval administration of nilestriol could significantly increase the numbers of bone marrow hematopoietic stem/progenitor cell counts (t =8.58,2.80,P ＜ 0.05) in mice on day 10 after 6.5 Gy irradiation.This also could be capable to significantly improve colony formation,with there being statistical difference compared with single administration(t =4.29,6.34,P ＜ 0.05).Also the administration at two-day-interval were also usefull in reconstruction of hematopoietic cell hyperplasia of bone marrow of irradiated mice.Conclusions As compared with conventional single admination,the pre-irradiation multiple administrations of nilestriol showed significantly improved radiation protection effects.Considering a nuclear medical emergency rescue,it is recommended to follow the pre-irradiation administration of nilestriol at two-day interval,which could obtain the best protection effects at minimum administration frequency.
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Objective To investigate whether 18F-FDG uptake can be applied in dosimetry to facilitate a rapid and accurate evaluation of individual radiation dosage after a nuclear accident. Methods Forty-eight Tibetan minipigs were randomly assigned into 6 groups, i.e., 0, 1, 2, 5, 8 and 11Gy groups. Animals in all except 0Gy group received total body irradiation (TBI) with a 8MV X centrifugal linear accelerator, and 18F-FDG combined positron-emission tomography and computed tomography (PET/CT) were carried out before TBI, and also at 6, 24 and 72h after receiving TBI in different doses ranging from 1 to 11Gy. Spleen tissues and blood samples were collected for histological examination, apoptosis, and routine blood analysis. Results Mean standardized uptake values (SUVs) of the spleen showed significant differences between experimental groups and control group. The spleen SUVs at 6h post-irradiation showed significant correlation with radiation dose; Spearman's correlation coefficient was 0.95(P18F-FDG uptake of spleen. This finding suggests that 18F-FDG PET/CT may be useful for the rapid detection of individual radiation dosage after acute radiation disease (ARD).
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Objective To investigate the effects of recombinant human granulocyte colonystimulating factor(G-CSF) on central and peripheral lymphocyte subset reconstitution after a sublethal dose of irradiation. Methods Sixty female BALB/c mice were given a 6.0 Gy γ-ray total body irradiation (TBI) and randomly divided into 2 equal groups. The mice in G-CSF + TBI group were injected subcutaneously with recombinant human G-CSF 100 μg·kg-1·d-1 for 14 d and the mice in TBI group were injected subcutaneously with the same volume of phosphate buffered solution (PBS) once daily for 14 d. 7,14,21, and 28 d later the mice were killed and their thymus were taken out to prepare of the mononuclear cell suspension to analysis the percentage of thymic CD4 + CD8 + double positive, CD4 +CD8 - single positive, CD4 - CD8 + single positive and CD4 - CD8 - double negtive cells by flow cytometry. Peripheral blood samples were collected from the caudal vein twice a week, and the white blood cell(WBC) counts and absolute number of lymphocytes were assessed by automatic hemocyte analyzer. 14,28, and 60 d later blood samples were collected from angular vein to examine the peripheral lymphocyte subsets by flow cytometry. Cell counting kit-8 was used to detect lipopolysaccharide (LPS) or concanavalin A (ConA) stimulated splenic lymphocyte proliferation. Results The percentage of thymic CD4 + CD8 +double positive cells decreased 7 d after irradiation, rebounded at 14 d, decreased again at 21 d, and then got a permanent recovery. 28 d after irradiation the percentage of thymic CD4 + CD8 + double positive cells in the G-CSF + TBI group recovered to normal and was significantly higher than that of the TBI group (t =12. 22, P < 0. 05). 21d after irradiation the percentage of thymic CD4-CD8 + single positive cells of the G-CSF + TBI group was significantly higher than that of the TBI group (t = 3.77, P < 0. 05). The peripheral WBCs and lymphocytes decreased to the lowest levels 7 d after irradiation and then gradually increased, however, WBCs and lymphoeytes of the G-CSF + TBI group began to recover earlier and faster than the TBI group. The proportion of CD3 + CD8 + T cells of the G-CSF + TBI group was significantly higher than that of the TBI group 14 and 60 d after irradiation (t =4. 31,5.78, P <0.05). But there was no significant difference in the proportion of CD3 + CD4 + T cells between the two groups. The proportion of B lymphoeytes of the G-CSF + TBI group was significantly lower than that of the TBI group 14 d after irradiation(t =7.30, P <0.05), but it recovered quickly, and there were no significant differences in the proportion of B lymphoeytes between the two groups 28 and 60 d after irradiation. The proliferation indexes of splenic lymphocytes in response to LPS and ConA in the G-CSF + TBI group were 4. 37 and 2.98 times higher than those in the TBI group 14 d after irradiation. Conclusions G-CSF could accelerate the recovery of central and peripheral lymphocyte subsets, raise the absolute number of lymphocytes, and enhance their proliferative function, which contributes to the central and peripheral immune reconstitution after acute irradiation.
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This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.
Subject(s)
Animals , Male , Mice , Acute Radiation Syndrome/drug therapy , Amifostine/pharmacology , Apoptosis/immunology , Gamma Rays/adverse effects , Hippocampus/immunology , Immunohistochemistry , In Situ Nick-End Labeling , Memory/radiation effects , Mice, Inbred ICR , Neurogenesis/immunology , Radiation-Protective Agents/pharmacologyABSTRACT
Objective The patients with lethal irradiation after sucessful hematopoietic stem cells transplan-tation had blood recovery, but did not avoid to died of multiple organ failure(MOF). To overcome the block, the article investigated mechanisms of mesenchymal stem cells (MSCs) protecting lethal radiated mice from multiple organ failure after haploid bone marrow cells transplantation. Method BALB/c mice irradiated with 8Gy60COγ-rays were randomly divided into two groups: MSCs group, infused MSCs labeled with cm-DiI and bone marrow monocytes of CB6F1 mice; Control group, only infused bone marrow monocytes; normal group, mice were infused cm-DiI marked MSCs without irradiation. The distribution of MSCs and the serous densities of Il-2, Il-10 and TNF-α in the recipients were observed after transplantation. Results MSCs collected in the bone marrow and the intes-tine in normal group at 15 d,in MSCs group MSCs enriched the different organs at 3,15 and 30 d. MSCs regulated down the secretion of IL-2 and TNF-α,and up the IL-10 density. Conclusions MSCs protected mice from multiple organ failure through above effects and may be open a new treatment strategy on acute radiation syndrome by stem cells.
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Objective To investigate the mechanism of mesenchymal stem cells in enhancing the effects of haploid matched bone marrow cells transplantation in mice with acute radiation syndrome(ARS).Methods The survival of mice infused with difierent levels of MSCs and bone marrow cells after 8 Gy TBl were examined.BALB/c female mice irradiated with 8 Gy of 60Co γ-rays were randomly divided into two groups,MSCs group,infused with MSCs of female CB6F1 mice labeled with cm-DiI and bone marrow monocytes of male CB6F1,Control group,only infused with bone marrow monocytes.Peripheral blood counts,T-lymphocyte subpopulation of peripheral blood cells,the sry-gene chimerism of bone marrow of the receiptors,the distribution of MSCs in the receiptors,the occurrence time of cGVHD,pathologic variety of medulla were observed.Resuits MSCs improved the survival of mice after 8 TBI,but 1.5×108/kg of MSCs increased the mortality of irradiated mice.In comparison with the control group,leukocytes and plastocytes recovered rapidly in MSCs group.Megacaryocytes in sternum marrows grew fastly in MSC group.The percent of CD3 and CD4 positive cells in the MSCs group were hisher than those in control post-transplantation.The sry-gene chimerism of bone marrow of the receiptors was higher in the MSCs group than that in the control at 30 d.The MSCs were distributed in intestine,thymus,bone marrow,liver,heart of the receiptors at 30 d.The cGVHD occurrence was 30 d later in MSCs group than that of the control.Conclusions MSCs could improve stem cell engraftment,enhance T-lymphocyte and plastocytes recevery,delay occurrence of cGVHD,repair injured organs and increase survivals.It is indicated that MSCs can enhance the treatment effects of haploid hematopoietic stem cells transplant for ARS.
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The ARS(Acute Radiation Syndrome) develops, within 60 days after exposure to ionising radiation with typical clinical signs and symptoms as a function of time. The interactions and combined effects of radiation-induced damage to different organ systems are diverse and not yet fully understood. Therefore, when accidental exposure to ionising radiation is documented or suspected, guidance for immediate diagnostic procedures and specialised care are required to handle the complexity of the ARS. The following four organ systems, Neurovascular system (N), Hematopoietic system (H), Cutaneous system (C) and Gastrointestinal system (G) are considered to be of critical significance for the development of ARS and should therefore receive special attention in the medical management of radiation accident cases. The Assessment of the severity of damage, Decision on the kind of hospitalisation, Provision of appropriate therapeutic interventions and Evaluation of the patient's prognosis must be considered in the management of a patient after a radiation accident. When significant levels of radioactive materials are incorporated, pathological consequences may ensue, making emergent treatment particularly important. However, this should not take priority over treatment of life threatening conditions and of acute injuries. Following medical stabilization, careful radiological assessment can be performed to determine the presence of both external and internal contamination. It is important to note that 1) contaminated patients do not represent a direct hazard to health care providers and 2) lifesaving procedures should not be delayed regardless of the level of contamination.