Radiation Combined Injury Research Articles

Assessment of the readiness of the medical and preventive facility for actions in an extraordinary situation of a military character with combined radiation injury to the population

Background. In emergency situations of a military nature, medical institutions at all levels, especially specialized (radiological) medical facilities, are tasked with providing qualified assistance to the affected population. The effectiveness of these measures depends not only on the promptness, equipment, and training of operational teams but also on adherence to radiation safety standards, which differ from peacetime norms in terms of the scale of combined radiation injuries, injury criteria, and the methods of implementing measures. At the same time, against the backdrop of the multi-criteria uncertainty of possible radiological scenarios, there is no scientific justification for the necessary connections between the features of radiation safety and specific organizational and technical tasks within the system of overall readiness of medical institutions. Purpose – scientifically justify the potential readiness of a medical institution to act during a special period to provide qualified assistance to the population with combined radiation injuries, based on a systematic analysis of the features of the radiation safety system during military emergencies. Materials and Methods. In this paper, an attempt is made to assess the readiness of a medical and preventive institution to take action in emergency situations of a military nature by applying the method of analysis of hierarchies by T. Saati, adapted for the relevant tasks. Results. The conducted analysis of generalized weight coefficients and priorities in percentages (%) for each element of the hierarchical structure (Fig. 3) shows that more than 50% of «actions» are related to the effective provision of personnel safety and the effective delivery of medical care («Dia-1» and «Dia-2»). These components should receive key attention in the practical training of healthcare facility personnel and involved individuals through special training for emergency actions during special periods. Conclusions. This work attempts to assess the readiness of a medical institution to act in military emergencies by applying the Analytic Hierarchy Process (AHP) method by T. Saaty, adapted for the relevant tasks.

An Overview of Radiation Countermeasure Development in Radiation Research from 1954 to 2024.

Preparation for medical responses to major radiation accidents, further driven by increases in the threat of nuclear warfare, has led to a pressing need to understand the underlying mechanisms of radiation injury (RI) alone or in combination with other trauma (combined injury, CI). The identification of these mechanisms suggests molecules and signaling pathways that can be targeted to develop radiation medical countermeasures. Thus far, the United States Food and Drug Administration (U.S. FDA) has approved seven countermeasures to mitigate hematopoietic acute radiation syndrome (H-ARS), but no drugs are available for prophylaxis and no agents have been approved to combat the other sub-syndromes of ARS, let alone delayed effects of acute radiation exposure or the effects of combined injury. From its inception, Radiation Research has significantly contributed to the understanding of the underlying mechanisms of radiation injury and combined injury, and to the development of radiation medical countermeasures for these indications through the publication of peer-reviewed research and review articles.

3D skin bioprinting as promising therapeutic strategy for radiation-associated skin injuries.

Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.

Product Development within the National Institutes of Health Radiation and Nuclear Countermeasures Program.

The Radiation and Nuclear Countermeasures Program (RNCP) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) was established to facilitate the development of medical countermeasures (MCMs) and diagnostic approaches for use in a radiation public health emergency. Approvals for MCMs can be very challenging but are made possible under the United States Food and Drug Administration (FDA) Animal Rule, which is designed to enable licensure of drugs or biologics when clinical efficacy studies are unethical or unfeasible. The NIAID portfolio includes grants, contracts, and inter-agency agreements designed to span all aspects of drug development and encompasses basic research through FDA approval. In addition, NIAID manages an active portfolio of biodosimetry approaches to assess injuries and absorbed radiation levels to guide triage and treatment decisions. NIAID, together with grantees, contractors, and other stakeholders with promising products, works to advance candidate MCMs and biodosimetry tools through an established product development pipeline. In addition to managing grants and contracts, NIAID tests promising candidates in our established preclinical animal models, and the NIAID Program Officers work closely with sponsors as product managers to guide them through the process. In addition, a valuable benefit for stakeholders is working with the NIAID Office of Regulatory Affairs, where NIAID coordinates with the FDA to facilitate interactions between sponsors and the agency. Activities funded by NIAID include basic research (e.g., library screens to discover new products, determine early efficacy, and delineate mechanism of action) and the development of small and large animal models of radiation-induced hematopoietic, gastrointestinal, lung, kidney, and skin injury, radiation combined injury, and radionuclide decorporation. NIAID also sponsors Good Laboratory Practice product safety, pharmacokinetic, pharmacodynamic, and toxicology studies, as well as efficacy and dose-ranging studies to optimize product regimens. For later-stage candidates, NIAID funds large-scale manufacturing and formulation development of products. The program also supports Phase 1 human clinical studies to ensure human safety and to bridge pharmacokinetic, pharmacodynamic, and efficacy data from animals to humans. To date, NIAID has supported >900 animal studies and one clinical study, evaluating >500 new/repurposed radiation MCMs and biodosimetric approaches. NIAID sponsorship led to the approval of three of the six drugs for acute radiation syndrome under the FDA Animal Rule, five Investigational New Drug applications, and 18 additional submissions for Investigational Device Exemptions, while advancing 38 projects to the Biomedical Advanced Research and Development Authority for follow-on research and development.

Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation

Purpose This research endeavor was undertaken to elucidate the impact of an innovative ascorbate formulation on the regeneration process of full-thickness excision wounds in a rat model exposed to whole-body gamma irradiation, replicating conditions akin to combat or radiation emergency scenarios. Materials and Methods We established a comprehensive rat model by optimizing whole body γ-radiation doses (5–9 Gy) and full-thickness excision wound sizes (1–3 cm2) to mimic radiation combined injury (RCI). The developed RCI model was used to explore the healing potential of ascorbate formulation. The study includes various treatment groups (i.e., sham control, radiation alone, wound alone, radiation + wound, and radiation + wound + formulation). The ascorbate formulation was applied twice daily, with a 12-hour gap between each application, starting 1 hour after the initiation of the wound. The healing potential of the formulation in the RCI context was evaluated over 14 days through hematological, molecular, and histological parameters. Results The combination of a 5 Gy radiation dose and a 1 cm2 wound was identified as the optimal setting to develop the RCI model for subsequent studies. The formulation was used topically immediately following RCI, and then twice daily until complete healing. Treatment with the ascorbate formulation yielded noteworthy outcomes and led to a substantial reduction (p < .05) in the wound area, accelerated epithelialization periods, and an increased wound contraction rate. The formulation’s localized healing response improved organ weights, normalized blood parameters, and enhanced hematopoietic and immune systems. A gene expression study revealed the treatment up-regulated TGF-β and FGF, and down-regulated PDGF-α, TNF-α, IL-1β, IL-6, MIP-1α, and MCP-1 (p < .05). Histopathological assessments supported the formulation’s effectiveness in restoring cellular architecture and promoting tissue regeneration. Conclusion Topical application of the ascorbate formulation in RCI resulted in a significant improvement in delayed wound healing, leading to accelerated wound closure by mitigating the expression of inflammatory responses.

Experimental Study of the Effectiveness of Naphazoline and Co-Administration of Filgrastim in Combined Radiation Injury

Experimental Study of the Effectiveness of Naphazoline and Co-Administration of Filgrastim in Combined Radiation Injury

МЕДИЦИНСКИЕ ПОСЛЕДСТВИЯ РАДИАЦИОННЫХ АВАРИЙ НА АТОМНЫХ ПОДВОДНЫХ ЛОДКАХ СССР

Purpose: To analyze the health effects of onboard radiation accidents in the Soviet nuclear submarines. Results: Over the entire operation period of Soviet nuclear submarines, eight severe accidents occurred related to nuclear power installations. These accidents occurred in a confined space and the associated radiation situation is more complex than in other conditions; therefore, health effects of such accidents are more significant. There were two types of onboard accidents: thermal accidents (five cases) associated with a failure during heat removal from the reactor core; and accidents (three cases) caused by a partial chain reaction. The first type of accidents occurred during the route operation of nuclear submarine, and the second one – during repair work. Thermal accidents were associated with varying degrees of depressurization of the primary circuit of the reactor, which increased the gamma and beta background due to the entry into the compartment of a large amount of radioactive noble gases (hereinafter – RBGs) and radioactive aerosols. It has been shown that in the confined space of nuclear submarines, RBG isotopes (mainly 85Кr, 133Хе, 135Хе) make a significant contribution to the individual dose and the skin is a critical organ. Conclusion: An analysis of the health effects of thermal onboard accidents showed that radiation injuries were caused by external gamma- and beta-exposure, as well as the ingestion of radioactive aerosols. If accidents are accompanied by prolonged minor leaks leading to entry of RBG into the compartment, the main contribution is made by beta-exposure and the skin is a critical organ. If there is a simultaneous inflow of coolant into the compartment, combined radiation injuries are formed and, in this case, skin lesions aggravate the acute radiation sickness. In accidents induced by a partial chain reaction, the main radiation factor is external γ-n-exposure during an outbreak of a partial chain reaction, and in the case of a thermal explosion, a traumatic factor also affects a person, leading to injuries of varying severity in the victims.

ОСОБЕННОСТИ КЛИНИЧЕСКИХ ПРОЯВЛЕНИЙ ПЕРВИЧНОЙ РЕАКЦИИ ПРИ КОМБИНИРОВАННОМ РАДИАЦИОННОМ ПОРАЖЕНИИ (РАДИАЦИОННОЕ ВОЗДЕЙСТВИЕ И МЕХАНИЧЕСКАЯ ТРАВМА ГОЛОВЫ)

Purpose: To describe, on the basis of literature data, the features of the primary reaction of a person with a combined radiation injury – radiation exposure and mechanical head injury – in order to substantiate the possibility of using the symptoms of the primary reaction to predict the severity of acute radiation sickness (ARS). Material and methods: Analysis of literature data. Results: Based on the literature data, the clinical symptoms of the primary reaction in human radiation damage in a different dose range, and traumatic brain injuries are described: – concussion of the brain; – mild brain injury; – moderate brain injury. To characterize the clinical picture of the combined effects of radiation injury and mechanical head injury, the symptoms of the primary reaction were compared with the symptoms of traumatic brain injury. Such symptoms of the primary reaction as vomiting, nausea, headache, dizziness in the most severe form of traumatic brain injury – a moderate brain injury – are diagnosed somewhat more often than in acute radiation sickness. In less severe forms of traumatic brain injury – concussion, mild brain injury – the frequency and severity of these symptoms are close to ARS. In the complex clinical picture of combined radiation exposure and traumatic brain injury, the most different symptoms of the two components of combined radiation damage are the state of consciousness and the characteristics of the skin. Conclusion: Clinical symptoms of the primary reaction to radiation exposure in conditions of combined radiation damage in the presence of head trauma lose their diagnostic significance for the early prognosis of the severity of developing ARS. In the clinical picture of combined radiation exposure and mechanical head injury, the most pronounced leading components should be the state of consciousness and the characteristics of the skin.

Principles of medical sorting of patients with combined radiation injuries in Russia and NATO countries (literature review)

Principles of medical sorting of patients with combined radiation injuries in Russia and NATO countries (literature review)

Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model.

Radiation-combined injury (RCI) augments the risk of morbidity and mortality when compared to radiation injury (RI) alone. No FDA-approved medical countermeasures (MCMs) are available for treating RCI. Previous studies implied that RI and RCI elicit differential mechanisms leading to their detrimental effects. We hypothesize that accelerating wound healing improves the survival of RCI mice. In the current study, we examined the effects of RCI at different doses on lethality, weight loss, wound closure delay, and proinflammatory status, and assessed the relative contribution of systemic and local elements to their delayed wound closure. Our data demonstrated that RCI increased the lethality and weight loss, delayed skin wound closure, and induced a systemic proinflammatory status in a radiation dose-dependent manner. We also demonstrated that delayed wound closure did not specifically depend on the extent of hematopoietic suppression, but was significantly influenced by the toxicity of the radiation-induced systemic inflammation and local elements, including the altered levels of proinflammatory chemokines and factors, and the dysregulated collagen homeostasis in the wounded area. In conclusion, the results from our study indicate a close association between delayed wound healing and the significantly altered pathways in RCI mice. This insightful information may contribute to the evaluation of the prognosis of RCI and development of MCMs for RCI.

Combined radiation burn injuries: A note

Combined radiation injury occurs when radiation is accompanied by any other form of trauma. The past experiences of Hiroshima, Nagasaki, and Chernobyl have revealed that a large number of victims of such nuclear accidents or attacks suffer from combined radiation injuries. The possibility of a nuclear attack seems very far-fetched, but the destruction that would occur in such an event would be massive, with a huge lossof lives. Therefore, preparedness for the same should be done beforehand. The severity of combined radiation depends upon various factors, such as radiation dose, type, tissues affected, and traumas. The article focuses on combined radiation burn injury (CRBI) which may arise due to the combination of ionising radiation with thermal burns. CRBI can have varied effects on different organs like the hematopoietic, digestive, lymphatic, cardiovascular, and respiratory systems. Some of the most profound lethal effects are hematopoietic dysfunction, gastrointestinal leakage, bacterial translocation to other organ sites, pulmonary fibrosis, and pneumonitis. In this article, we have attempted to accumulate the knowledge of ongoing research on the functioning of different organ systems, which are affected due to CRBI and possible countermeasures to minimize the effects, thus improving survival.

Neuropeptide dalargin: therapeutic potential

The main aim of the article is to draw attention to the real therapeutic potential of the neuropeptide dalargin as a remedy of radiological pharmacology as part of the repurposing of drugs, to give some examples of its clinical use that are not covered by domestic reviews. Dalargin is a synthetic analogue of the endogenous regulatory neuropeptide leucine-enkephalin and has the following structure: Tyr-D-Ala-Gly-Phe-Leu-Arg. The drug to some extent has wound healing, reparative, anti-inflammatory, antioxidant, lymphogenic, hypotensive, antiarrhythmic, endothelioprotective, cardioprotective, pulmoprotective, hepatoprotective, pancreatoprotective, hypocholesterolemic, antiatherosclerotic, antihypoxic, antiischemic, analgesic, antidepressant, antistress, immunomodulatory, anticarcinogenic, antitumor, antimetastatic, arteriolo- and venulodilating action; normalizes the activity of neuroendocrine subsystems: hypothalamic-pituitary-adrenal, sympathetic-adrenal; increases the glomerular filtration rate of the kidneys, significantly reduces the release of pro-inflammatory cytokines, prevents the development of acute respiratory distress syndrome [1,3,4, 6-18, 20-23]. The list of effects of dalargin makes it possible to formulate and predict new effects not listed above. Described usage of dalargin in diagnostic tests for MRI, perfusion single photon emission computed tomography and echocardiography, in the treatment of combined radiation injuries. Dalargin should be used to prevent the development of pathological processes / conditions in personnel when working in extreme conditions and in patients with comorbidity in surgery, combustiology, dentistry, oncology and traumatology.

Combined injury: irradiation with skin or bone wounds in rodent models

A radiation combined injury is defined as an injury that occurs in the setting of irradiation, such as those expected after a nuclear accident, radiation dispersal device release (a ‘dirty bomb’), or a nuclear weapon detonation. There is much research on irradiation-associated burns and their healing, but there is less known about other injuries sustained in the context of irradiation. Animal models are limited in their correlations to clinical situations but can support research on specific questions about injuries and their healing. Mouse models of irradiation with skin or bone wounds are validated as highly reproducible and quantitative. They show dose-dependent impairment of wound healing, with later recovery. Irradiation-induced delay of bone wound healing was mitigated to different extents by single doses of gramicidin S-nitroxide JP4-039, a plasmid expressing manganese superoxide dismutase, amifostine/WR2721, or the bifunctional sulfoxide MMS-350. These models should be useful for research on mechanisms of radiation dermal and osseous damage and for further development of new radioprotectors. They also provide information of potential relevance to the effects of clinical radiation therapies.

ПРОВЕДЕНИЕ САНИТАРНОЙ ОБРАБОТКИ НА ЭТАПАХ ОКАЗАНИЯ МЕДИЦИНСКОЙ ПОМОЩИ ПОСТРАДАВШИМ В РАДИАЦИОННОЙ АВАРИИ

Purpose: To summarize and analyze the results of research and practical recommendations on the decontamination of victims in the event of radiation accidents, including taking into account the authors’ experience gained in the initial period of the Chernobyl accident (April – August 1986) and in other local radiation accidents (incidents), as well as during emergency exercises.&#x0D; Results: The indications for carrying out decontamination and the technique of its implementation were considered, a comparative assessment of the effectiveness of skin decontamination agents was presented. Recommendations were formulated for determining the priority (urgency) of carrying out decontamination, depending on the level of external radioactive contamination of the victims. Criteria, rules and methods for carrying out decontamination were proposed for use in relation to the practice of medical and hygienic measures at the stages of medical evacuation (accident site, enterprise health center, enterprise sanitary inspection department, triage site, hospital admission department). The features of decontamination of victims with combined radiation injuries and contaminated wounds (burns) were considered, issues of ensuring the radiation safety of medical personnel who provide assistance to victims are touched upon.&#x0D; Conclusion: Timely and correctly performed decontamination reduces the exposure of the skin, prevents the entry of radioactive substances into the body and the transfer (spread) of radioactive substances to the subsequent stages of medical evacuation. The main criteria for the urgency (priority) of carrying out decontamination are the levels of radioactive contamination of the skin, contamination nature (radionuclide composition, physicochemical form, etc.) and the presence of victim’s skin lesions (wounds, burns). Decontamination of victims with high levels of radioactive contamination should be considered as a part of the first and subsequent emergency health care and should be carried out as prescribed or with the direct participation of a healthcare professional. At the stages of medical evacuation, decontamination can be carried out if the victim’s condition is stabilized. In the case of a serious condition of the victim, the priority is evacuation to a hospital, while in the prehospital period, as a rule, only partial decontamination of skin areas with high levels of contamination can be carried out. The procedure and rules for decontamination, including the use of skin decontaminating agents, should be reflected in the action plans of the personnel of radiation hazardous enterprises and the plans for medical support of medical units of the FMBA of Russia.

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. In the last 60 years, the investigators at AFRRI have conducted exploratory and developmental research with broad application to the field of radiation sciences. As the only DoD facility dedicated to radiation research, AFRRI's Medical Radiobiology Advisory Team provides deployable medical and radiobiological subject matter expertise, advising commanders in the response to a U.S. nuclear weapon incident and other nuclear or radiological material incidents. AFRRI received the DoD Joint Meritorious Unit Award on February 17, 2004, for its exceptionally meritorious achievements from September 11, 2001 to June 20, 2003, in response to acts of terrorism and nuclear/radiological threats at home and abroad. In August 2009, the American Nuclear Society designated the institute a nuclear historic landmark as the U.S.'s primary source of medical nuclear and radiological research, preparedness and training. Since then, research has continued, and core areas of study include prevention, assessment and treatment of radiological injuries that may occur from exposure to a wide range of doses (low to high). AFRRI collaborates with other government entities, academic institutions, civilian laboratories and other countries to research the biological effects of ionizing radiation. Notable early research contributions were the establishment of dose limits for major acute radiation syndromes in primates, applicable to human exposures, followed by the subsequent evolution of radiobiology concepts, particularly the importance of immune collapse and combined injury. In this century, the program has been essential in the development and validation of prophylactic and therapeutic drugs, such as Amifostine, Neupogen®, Neulasta®, Nplate® and Leukine®, all of which are used to prevent and treat radiation injuries. Moreover, AFRRI has helped develop rapid, high-precision, biodosimetry tools ranging from novel assays to software decision support. New drug candidates and biological dose assessment technologies are currently being developed. Such efforts are supported by unique and unmatched radiation sources and generators that allow for comprehensive analyses across the various types and qualities of radiation. These include but are not limited to both 60Co facilities, a TRIGA® reactor providing variable mixed neutron and γ-ray fields, a clinical linear accelerator, and a small animal radiation research platform with low-energy photons. There are five major research areas at AFRRI that encompass the prevention, assessment and treatment of injuries resulting from the effects of ionizing radiation: 1. biodosimetry; 2. low-level and low-dose-rate radiation; 3. internal contamination and metal toxicity; 4. radiation combined injury; and 5. radiation medical countermeasures. These research areas are bolstered by an educational component to broadcast and increase awareness of the medical effects of ionizing radiation, in the mass-casualty scenario after a nuclear detonation or radiological accidents. This work provides a description of the military medical operations as well as the radiation facilities and capabilities present at AFRRI, followed by a review and discussion of each of the research areas.

PEG-G-CSF and L-Citrulline Combination Therapy for Mitigating Skin Wound Combined Radiation Injury in a Mouse Model.

Radiation combined injury (RCI, radiation exposure coupled with other forms of injury, such as burn, wound, hemorrhage, blast, trauma and/or sepsis) comprises approximately 65% of injuries from a nuclear explosion, and greatly increases the risk of morbidity and mortality when compared to that of radiation injury alone. To date, no U.S. Food and Drug Administration (FDA)-approved countermeasures are available for RCI. Currently, three leukocyte growth factors (Neupogen®, Neulasta® and Leukine®) have been approved by the FDA for mitigating the hematopoietic acute radiation syndrome. However these granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) products have failed to increase 30-day survival of mice after RCI, suggesting a more complicated biological mechanism is in play for RCI than for radiation injury. In the current study, the mitigative efficacy of combination therapy using pegylated (PEG)-G-CSF (Neulasta) and -citrulline was evaluated in an RCI mouse model. L-citrulline is a neutral alpha-amino acid shown to improve vascular endothelial function in cardiovascular diseases. Three doses of PEG-G-CSF at 1 mg/kg, subcutaneously administered on days 1, 8 and 15 postirradiation, were supplemented with oral -citrulline (1 g/kg), once daily from day 1 to day 21 postirradiation. The combination treatment significantly improved the 30-day survival of mice after RCI from 15% (vehicle-treated) to 42%, and extended the median survival time by 4 days, as compared to vehicle controls. In addition, the combination therapy significantly increased body weight and bone marrow stem and progenitor cell clonogenicity in RCI mice, and accelerated recovery from RCI-induced intestinal injury, compared to animals treated with vehicle. Treatment with -citrulline alone also accelerated skin wound healing after RCI. In conclusion, these data indicate that the PEG-G-CSF and -citrulline combination therapy is a potentially effective countermeasure for mitigating RCI, likely by enhancing survival of the hematopoietic stem/progenitor cells and accelerating recovery from the RCI-induced intestinal injury and skin wounds.

Feasibility of nitric oxide synthesis inhibitor for the treatment of combined radiation injuries

The model of combined radiation-thermal injury (CRTI) in mice was experimentally and histologically verified: exposure to 60Co-radiation at a dose of 7 Gy (0.39 Gy/min) on the Agat device and the subsequent thermal effect on the GL6 device on the back, leading to the development of a 3B degree burn on 10% of the body surface. This model was used to confirm the positive influence of the NOS inhibitor T1023 on the course of CRTI. It was found that a single i.p. administration of T1023 72 h after CRTI application caused a nearly statistically significant (p = 0.051) increase in the 30-day survival rate of animals. The data obtained indicate the need for further detailed study of NOS inhibitor effects on the course of acute radiation syndrome (ARS) and CRTI.

Application of early necrectomy of a deep skin burn on rats with acute radiation syndrome of mild severity

The involvement of countries possessing nuclear weapons in local and regional armed conflicts poses a threat of use of nuclear weapon. In the case of this combined radiation injuries can make up to 70% of sanitary losses. The existing ideas about the methods of surgical treatment of combined radiation-thermal injures are contradictory and do not clearly provide procedure depending on the severity of injury or in non-classical forms of injury. The idea of the study was to estimate the effectiveness of performing an early necrectomy of a burn eschar after a two-factor injury, which includes modeling mild acute radiation syndrome in addition to a thermal burn on rats. A deep skin burn was simulated with hot water over an area of 10% of the body surface after total γ-irradiation at a dose of 3 Gy. Then after 3 h the burn eschar necrectomy was performed. It was established that the chosen method of surgical treatment of a deep burn significantly aggravates the severity of irradiated animals, which is manifested by the death of more than 50% of rats in the first 4 days after necrectomy. The operative trauma became the leading component of the combined injury formed and determined the severity of its course. Thus, the burn eschar necrectomy modifies a light two-factor radiation-thermal injury to a classic combined radiation injury. Despite the severe postoperative period, necrectomy significantly accelerates the healing of burn wounds in irradiated animals. This indicates the promise of finding methods for compensating abnormalities developing in the postoperative period in order to accelerate wound healing before the onset of radiation sickness and prevent infectious complications.

Potential Ways to Increase Body Resistance to Damaging Action of Ionizing Radiation with Radiomitigators

This review considers the potential mechanisms of radiomitigative effect of radioprotective drugs in interaction with pathophysiological processes accompanying radiation injury to tissues at the earliest stages of its development. Radiomitigators affect bodily systems throughout the development of primary radiation stress and inflammatory process upon the realization of radiation injury during the primary radiation reaction. Inflammation as a protective body reaction to pathogens represents a self-organized system that commits support and limits the intensity of its manifestation. For this reason, the implementation of the radioprotective effect of radiomitigators, including immunogens, proinflammatory cytokines, steroid hormones, biogenic amines, and purine nucleosides and their synthetic and natural analogs, which stimulate native immunity, depends on its initial state and the severity of radiation injury of the body. The inverse negative relation in response to the action of proinflammatory cytokines, which is manifested as induction of the synthesis of anti-inflammatory cytokines and hematopoietic growth factors (primarily, granulocyte colony–stimulating factor), promotes the activation of myelopoiesis and their antiapoptotic action. The interaction of the immunogen effect and radiation stress depends on pharmacodynamics and features of the realization of the radioprotective properties of drugs. The implementation of the action of radiomitigators depends on the functioning of the antioxidant system of the body, because it can be exhausted under the influence of inflammation. In this case, postradiation oxidative toxemia induces injuries to vital parenchymatous organs. This is observed under the influence of proinflammatory cytokines at combined radiation injuries. All of the listed groups of radiomitigators have identical radioprotective activity (DRF = 1.2–1.3). The absence of expressed side effects, good tolerance of radiomitigators by humans, and the duration of their possible effective application after irradiation are the key indices for assessment of their prospects in radiation accidents.

DTMP-GH Fusion Protein Therapy Improves Survival after Radiation Injury Combined with Skin-Burn Trauma in Mice.

Exposure to ionizing radiation combined with traumatic tissue injury is an important life-threatening condition found in the civilian populations after nuclear and radiological events. The significance feature of radiation combined injury (RCI) is the severe combined effect, which makes the injury more complicated. At present, there are limited measures available to treat RCI. Here we show that a chimeric protein dTMP-GH, fusing human growth hormone (hGH) with a tandem dimer of thrombopoietin mimetic peptide (dTMP), could be an effective therapy agent for RCI in a mice model. In this study, using a RCI mouse model exposed to 60Co γ-ray photons (6.0 Gy, 0.3 Gy/min) followed by a 20% total-body-surface-area burns (henceforth called: RB-CI) was established. Administration of dTMP-GH (200 ug/kg) for 10 consecutive days beginning at 24 h after injury improved survival rate during a 30-day observation period compared with the control vehicle group. dTMP-GH treatment also showed enhanced bone marrow hematopoiesis recovery determined by peripheral blood analysis and bone marrow histopathology. Meanwhile, dTMP-GH treatment accelerated skin wound closure and mitigated ileum injury in the RCI model. These results suggest that dTMP-GH may prove to be an effective therapeutic drug for RCI.