Medical Radiology and Radiation Safety. 2024. Vol. 69. № 3

 

PROMISING ASPECTS OF MEDICAL-BIOLOGICAL SCIENCE AND PRACTICE –

TO THE 100TH ANNIVERSARY OF A.K. GUSKOVA: ADDRESS TO DOCTORS AND SCIENTISTS

 

 

Angelina Konstantinovna Guskova

Doctor of Medical Sciences, Professor, Corresponding Member. RAS

March 29, 1924 – April 7, 2015

 

Guskova Angelina Konstantinovna (1974-2015) – 41 years of scientific and creative leadership of the Clinical Department of Radiation Medicine: Head of the Clinical Department of Radiation Medicine (1974–1996), Chief Researcher (1996–2015). In one of the sections of the book she wrote, “The Nuclear Industry of the Country Through the Eyes of a Doctor” (2004), in the chapter Instead of a conclusion - “Hear the call of the future!”, Angelina Konstantinovna presented aspects of medical and biological science, which, taking into account the accumulated data, can become, in her opinion, , the most promising for the future and require priority development in our country, in the FMBC named after. A.I. Burnazyan and in the Clinical Department of Radiation Medicine, in particular, in connection with the radically changed “set” of the main operating factors in the normal operation of all nuclear enterprises, especially in terms of the specific importance of the radiation component. At the same time, there must be a constant readiness to take adequate action in the event of an emergency situation and, especially, a large-scale radiation accident.

What aspects of medical and biological science, taking into account the accumulated data, can become the most promising for the future and require priority development? Based on the type of work of RERF branches, which were created not in the capital of Japan, but in cities affected by an atomic explosion, systematic, multi-year work should be organized to improve and maximize the filling of the medical and dosimetric register of the industry on the basis of its main enterprises of the nuclear industry and energy industry of Rosenergoatom .

The role of the clinical department of radiation medicine at the central institute in Moscow will be different than before. It should be focused on:

1. Supplementation with dynamic observation data on industry-trained workers working for a long time in contact with ionizing radiation in the nuclear industry and energy sector and closed administrative towns.

2. Formation of periodically changing industry nosological registers (cardiocerebrovascular pathology, psychosomatic diseases, etc.) for targeted clinical study of issues that arise but are not resolved within the framework of dosimetric industry registers.

3. Introduction to the database of information about rarer forms of occupational pathology, which were naturally concentrated earlier in the IBP blade (diseases from exposure to plutonium, polonium, beryllium, dust and toxic bronchopulmonary diseases). It is justified to preserve the sectoral Chernobyl data archive, which operates quite successfully both independently and as a complex in the RSMDR in Obninsk.

Thus, completeness of materials on the long-term consequences of occupational exposure in a wide range of doses and exposure conditions will be ensured (together with the data of qualified hygienists and biophysicists presented in their section). Reasoned assessments of the clinical validity of accepted standards and risk values, especially for situations of long-term chronic exposure, will be given. The contribution of radiation exposure to the complex of long-term health risks for personnel and descendants will be determined.

Another area that requires development and modern technical and drug support is the improvement of clinical programs to provide assistance in case of radiation accidents of various sizes, which are always possible in the industry. The occurrence of chronic diseases can be prevented, but the potential for local and general acute effects in humans cannot be excluded.

An adequate clinical model of these conditions, which allows one to improve the professional level and develop new promising therapeutic agents, is primarily oncohematological diseases. In their intensive care programs, the same techniques and means are used as for radiation sickness: transplantation of hematopoietic cells, growth factors and other means of treating the main complications (infections, multiple organ failure).

This area includes problems of diagnostics and therapy, the most common local radiation injuries in real conditions, with its own scope of diagnostic and therapeutic techniques and the provision of the possibility of retrospective reconstruction of radiation doses.

It is advisable to preserve and develop the work of the experimental group for preclinical testing of drugs and testing ideas that arise during clinical observations.

For the clinic of severe occupational injuries and especially the assessment of subclinical forms of reaction to chronic exposure, methodological guidance on targeted modification of the scope of research during routine and unscheduled medical examinations is of particular relevance. At the same time, the range of techniques based on modern technologies is expanding, and the possibilities for quantitative assessment of a huge volume of information are increasing.

Transformation of directions will require a certain reorientation of medical personnel and a painful “cut-off” of some unpromising structures in institutions. But this should be done, and as soon as possible, including in our institute.

There is a huge, labor-intensive work ahead with the clinical archive, with the digitization of primary documentation. It is necessary to transfer into digital format the most significant part of the information from databases, from medical records and journals (dosimetric and biophysical indicators of specific patients). First of all, this applies to verified cases of radiation sickness and thoughtful expert opinions denying this diagnosis.

References to literature and texts of exam programs for the section of clinical and experimental radiobiology need to be revised and updated. At the same time, it is necessary, due to the growth in the volume of information and the improvement of information technology, to publish collections and books in various electronic formats, and also to use CDs, flash drives and computer hard drives to store information.

Create separate lists and annotations of thematic bibliographies for monographs and publications of a programmatic nature, completed in specialized scientific institutions at the proper methodological level.

The nuclear industry promptly collected and published the personalities of its leading specialists. In radiation medicine and radiobiology, there are only a few fragmentary attempts to fill this gap (S.P. Yarmonenko, partially L.D. Lindenbraten - mainly in the field of medical use of radiation).

There is another pressing issue - the selection and training system to ensure adequate activities of medical units and research institutes serving enterprises in the nuclear industry, energy and specialized scientific institutions based on research reactors and accelerators. The competence of those who currently train specialists in radiation medicine for civil defense services, military medicine and the Ministry of Emergency Situations is hardly adequate.

It should be borne in mind that the “set” of the main operating factors has radically changed under the conditions of normal operation of all nuclear enterprises, especially in terms of the specific significance of the radiation component. The Ministry of Health of the Russian Federation needs to introduce the qualification of a doctor in the specialty “Radiation Medicine”. At the same time, there must be a constant readiness to take adequate action in an emergency situation, and especially in a large-scale radiation accident.

Under these conditions, the training of specialists in the following main options is justified:

Doctors to work in emergency teams and in specialized beds at the nearest and main hospital, where assistance will be provided to victims from the first hours to days after exposure until complete recovery;

Doctors providing clinical examination of contingents working under normal operating conditions of an industry enterprise and (or) living in the region where they are located. This also applies to a routine outpatient medical appointment, as well as, to some extent, the first measures after an emergency situation occurs in the region or a signal about it is received.

Every modern doctor of any specialty working in a hospital or clinic needs a minimum of information on the usual situation in the region and the basic rules for emergency actions in the event of an accident.

The doctor must also be aware of the potential sources of radiation hazard where he works and lives, must know the main manifestations of radiation sickness and MLP, first aid measures, addresses of institutions where he can seek advice and refer victims for consultation with specialists.

Doctors preparing to work in emergency conditions must constantly work in the inpatient department of a large multidisciplinary hospital - as hematologists, infectious disease therapists, transfusiologists,

clinical laboratory assistants who are proficient in methods of taking material from bone marrow and peripheral blood and analyzing them. Surgeons must work permanently in burn departments or in traumatology and plastic surgery departments. However, additional training is also necessary for all of them in courses in occupational pathology and radiation medicine with confirmation of training by the corresponding periodically updated certificate documents. The emergency team also includes specialist hygienists and physicists, most often from municipal SES or specialized institutes located in the region. Since the work is carried out under the guidance of the chief doctors of the hospital and clinic, this dictates the need for special training and health care organizers.

These are the formal criteria by which doctors are selected and the basic minimum requirements for their training. However, in addition to professional culture, social and labor motivation to work in the specified profile, as well as the personal qualities of the doctor, become of great importance. After all, in essence, it will operate within the system of activities of the Ministry of Emergency Situations. The doctor must be inquisitive, active, active, decisive and at the same time possess a certain set of skills for orientation in a radiation environment, diagnostic techniques and methods of providing emergency care according to clinical indications under conditions of simultaneous exposure to radiation and other factors. Having orientated himself in the situation, he must be able to reassure patients and explain to the people involved in the accident the rules of their behavior, as well as provide transportation to the appropriate medical institution for those in need.

A targeted interview and examination of the patient (or group of people who had contact with the source), especially children, allows the necessary measures to be taken urgently to detect and isolate the source. It becomes possible to at least roughly assess the degree of danger, take urgent measures to minimize possible, sometimes very serious consequences, and hospitalize the victim in an institution where he will be provided with qualified assistance in full. Sometimes these people do not find adequate help for a long time, even in the presence of already obvious signs of radiation damage, and the investigation proceeds, as it were, in the reverse order: the disease is the source. Sometimes, on the contrary, information about contact with a source or its presence (in a school classroom, living room, museum) initiates a search for people who had contact with it, and helps to identify among a large group of participants in the situation the few people who are actually affected.

The only world-famous radiation medicine clinic in the country, capable, but very limited in its ability to provide assistance to victims of radiation, languishes a miserable existence. The significance of the medical and scientific potential of its specialists in the problem of ensuring the country's security is undeniable. But significant targeted reinforcement of its resources is required in terms of equipment, medicines, and payment for highly specialized personnel, whose activities may be urgently needed by the country in emergency circumstances such as the Chernobyl accident.

M. Montaigne also said that a fruitful and natural desire of society is the ability to listen to scientists. It is probably necessary for the country's leadership to find time for this and listen to the opinion of scientists - specialists in radiation medicine, taking into account the threat of nuclear terrorism and the expanding list of countries that own nuclear weapons in the modern world. The Ministry of Health of the Russian Federation needs to introduce the qualification of a doctor in the specialty “Radiation Medicine”.

 

Metlyaeva N.A.
Scientific Secretary of the Clinical Department
Radiation Medicine, Doctor of Medical Sciences, Associate Professor

 

 

 

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Medical Radiology and Radiation Safety. 2024. Vol. 69. № 2

DOI:10.33266/1024-6177-2024-69-2-12-17

J.M. Rozenberg, V.V. Maximov, D.V. Kuzmin, S.V. Leonov

Mechanisms of Mitochondrial Influence on Tumor Radioresistivity

Institute of Biophysics of the Future, Moscow Region, Dolgoprudny, Russia

Contact person: S.V. Leonov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

ABSTRACT

Radiotherapy remains one of the main methods of cancer treatment. At the same time, the formation of radioresistance (RR)of cancer cells to ionizing radiation leads to a loss of therapy effectiveness. The toxicity of radiotherapy is determined by mitochondria, and the use of mitochondria or their components in combination with chemo-radio and immunotherapy can increase the effectiveness of treatment. In this review, we have reviewed new, experimental methods for using mitochondria in cancer therapy. Literature data indicate that although the physiological transport of mitochondria promotes carcinogenesis and resistance to chemotherapy, transplantation of exogenous mitochondria, on the contrary, induces radiosensitivity and inhibits tumor growth in mouse models of cancer. Therefore, inhibition of endogenous transfer of cancer mitochondria or the development of methods for the delivery of exogenous mitochondria is a promising area for the development of anti-cancer drugs.

Keywords: radioresistance, cancer, mitochondrial transfer, mitochondrial transplantation

For citation: Rozenberg JM, Maximov VV, Kuzmin DV, Leonov SV. Mechanisms of Mitochondrial Influence on Tumor Radioresisti-
vity. Medical Radiology and Radiation Safety. 2024;69(2):12–17. (In Russian). DOI:10.33266/1024-6177-2024-69-2-12-17

 

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 PDF (RUS) Full-text article (in Russian)

 

Conflict of interest. The authors declare no conflict of interest.

Financing. The research was carried out with the financial support of a grant from the Russian Science Foundation (No. 23–14–00220).

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.11.2023. Accepted for publication: 27.12.2023.

 

 

 

Medical Radiology and Radiation Safety. 2024. Vol. 69. № 2

DOI:10.33266/1024-6177-2024-69-2-5-11

T.R. Gaynutdinov^{1, 2}, K.N. Vagin^{1, 2}, S.A. Ryzhkin^{1 ,2, 3, 4, 5}, F.H. Kalimullin¹,
S.E. Ohrimenko^{3, 6}

Modeling of Radiation Damage on the Background of Pasteurellosis Infection of the Organism

¹ Federal Center for Toxicological, Radiation and Biological Safety, Kazan, Russia

² Kazan Federal University, Kazan, Russia

³ Russian Medical Academy of Continuing Professional Education, Moscow, Russia

⁴ Kazan State Medical University, Kazan, Russia

⁵ Academy of Sciences of the Republic of Tatarstan, Kazan, Russia

⁶ A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: Timur Rafkatovich Gaynutdinov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .

 

ABSTRACT

Purpose: Simulate radiation-pasteurellosis lesions in the body.

Material and methods: Modeling of radiation and pasteurellosis lesions caused by the action of physical and biological factors on the organism Modeling of acute radiation disease (ARD) of animals was carried out by gamma-irradiation at the “Puma” facility with an exposure dose rate of 2.36×10^-5 A/kg. Pasteurella multocida, the causative agent of pasteurellosis, as one of the most frequently occurring pathogenic agents, was used as a model biological agent to reproduce the experimental biological lesion. Modeling of radiation-pasteurellosis lesion was carried out on rabbits and on white mice with live weight of 2.8‒3.4 kg and 18‒20 g, respectively.

Results: In experiments on white mice to determine the optimal doses of the affecting agents it was found that the minimum doses of gamma rays and the causative agent of pasteurellosis are 6.0 Gy and 4.5×10³ microbial cells per kg (m.k./kg), 3.9 Gy and 9.0×10³ m.k./kg, which leads to the development of pasteurellosis infection and radiation sickness in acute form with death of all animals, mainly on the first and second days after exposure to the affecting agents. k./kg, which leads to the development of pasteurellosis infection and radiation disease in acute form with death of all animals, mainly on the first and second days after combined exposure to the affecting agents. It was found that gamma-irradiation of rabbits at a dose of 8.0 Gy, followed by infection with Pasteurella at a dose of 4.5×10³ m.k./kg, aggravated the course of the pasteurellosis process, contributed to its generalization and accelerated the death of animals.

Conclusion: Radiation-pasteurellosis affection proceeded rapidly. Animals died on 2‒13 days after the onset of the disease with an average life expectancy of 6.3 days. Exposure of rabbits to non-lethal doses of the studied agents at the indicated doses led to aggravation of the course of radiation sickness and pasteurellosis infection, causing death of all animals from radiation-pasteurellosis pathology. At autopsy of corpses of animals, which died from acute course of radiation-pasteurellosis pathology, swelling of subcutaneous tissue in the area of pharynx and intermandibular space of neck, hyperemia and enlargement of lymph nodes, numerous hemorrhages on serous and mucous membranes and in tissues of parenchymatous organs ‒ serous or serous-fibrinous exudate in thoracic and abdominal areas, pulmonary edema were found.

Keywords: modeling, acute radiation sickness, pasteurellosis, combined damage, rabbits, mice

For citation: Gaynutdinov TR, Vagin KN, Ryzhkin SA, Kalimullin FH, Ohrimenko SE. Modeling of Radiation Damage on the Background of Pasteurellosis Infection of the Organism. Medical Radiology and Radiation Safety. 2024;69(2):5–11. (In Russian). DOI:10.33266/1024-6177-2024-69-2-5-11

 

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 PDF (RUS) Full-text article (in Russian)

 

Conflict of interest. The authors declare no conflict of interest.

Financing. The work was carried out at the expense of the funds of the subsidy allocated by the Federal State Budgetary Scientific Institution «Federal Center for toxicological, radiation and biological safety» for the performance of research work, state registration No. 01200202604.

Contribution. T.R. Gaynutdinov – a literary review on the topic of the article was conducted, the experimental part of the work was performed, the received material was processed, the text was edited, the manuscript was prepared. K.N. Vagin – advisory assistance was provided on the implementation of research. S.A. Ryzhkin – scientific guidance. F.H. Kalimullin – assistance and execution of the experimental part of the work. S.E. Okhrimenko – provided advisory assistance in the implementation of the experimental part of the work.

Article received: 20.11.2023. Accepted for publication: 27.12.2023.

 

 

 

 

Medical Radiology and Radiation Safety. 2024. Vol. 69. № 2

DOI:10.33266/1024-6177-2024-69-2-18-23

L.A. Romodin¹, O.V. Nikitenko^{1, 2}, T.M. Bychkova^{1, 2}, Yu.A. Zrilova¹,
E.D. Rodionova³, D.A. Bocharov³

Comparison of the Radioprotective Properties of Riboxin (Inosine)
and Indralin with Prophylactic Administration at Dosages
of 100 mg/кg According to the Survival Criterion of Irradiated Mice

¹ A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

² Institute of Biomedical Problems, Moscow, Russia

³ Russian Biotechnological University, Moscow, Russia

Contact person: L.A. Romodin, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

ABSTRACT

Relevance: Due to the high chemical toxicity of all known effective radioprotectors, studies of the radioprotective properties of safer drugs are very relevant. A sufficient number of works are devoted to the radioprotective properties of ribonucleoside riboxin (inosine). However, studies comparing the direct radioprotective properties of riboxin and a recognized radioprotector, for example, indralin, using a survival test in irradiated animals have not yet been carried out.

Purpose: Conduct a comparative assessment of the radioprotective properties of riboxin and indralin using a survival test in mice exposed to external X-ray radiation.

Material and methods: The experiment was carried out on 200 male ICR (CD-1) mice of the SPF category in duplicate. In each experiment, the animals were divided into the following groups, separated by body weight, 10 animals each: vivar control, not exposed to drugs and radiation, radiation control, with preliminary intraperitoneal administration of sterile water and exposed to external X-ray radiation in doses of 6.0, 6.5 and 6.75 Gy, experimental groups exposed to irradiation in the indicated doses with preliminary intraperitoneal administration of riboxin at a dosage of 100 ml/kg body weight or indralin at a dosage of 100 ml/kg. Survival was assessed for 30 days after irradiation. The dose change factor was determined using probit analysis as the ratio of the radiation dose causing the death of half of the irradiated animals that received the drug to the radiation dose causing the death of half of the irradiated animals without administration of the drug.

Results: The use of indralin before X-ray irradiation in doses of 6.0 Gy, 6.5 Gy and 6.75 Gy led to a statistically significant increase in the survival of animals compared to the group receiving Riboxin and control irradiation (р<0,05, log-rank test). Using equations derived from Phinney probit analysis, LD₅₀ doses were calculated for indralin and riboxin, from which dose change factors were calculated to be 1.8 and 1.07, respectively.

Conclusion: Since riboxin has not demonstrated radioprotective properties, its preventive use with intraperitoneal administration under the conditions described in this paper, for leveling the effects of radiation can be considered ineffective.

Keywords: ionizing radiation, external irradiation, mice, riboxin, inosine, indralin, dose change factor

For citation: Romodin LA, Nikitenko OV, Bychkova TM, Zrilova YuA, Rodionova ED, Bocharov DA. Comparison of the Radioprotective Properties of Riboxin (Inosine) and Indralin with Prophylactic Administration at Dosages of 100 mg/кg According to the Survival Criterion of Irradiated Mice. Medical Radiology and Radiation Safety. 2024;69(2):18–23. (In Russian). DOI:10.33266/1024-6177-2024-69-2-18-23

 

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Conflict of interest. The authors declare no conflict of interest.

Financing. The research was carried out at the expense of a grant from the Russian Science Foundation No. 23-24-00383, https://rscf.ru/project/23-24-00383 /.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.11.2023. Accepted for publication: 27.12.2023.