[Radiation-protective agent and anti-aging agents: random and predictable matches.]

Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and indirect antioxidant activities, inhibition of free radicals formation, increase resistance to stress impacts at the cellular level, acceleration of DNA reparation, prevention of chronic diseases linked to abnormalities in regeneration processes, activation of immune inflammatory processes and carcinogenesis. Regulation of cell cycle and apoptosis can often be considered as an implementing driver of radiation-protective and anti-aging activities. On the one hand, against the background of stopping the cell cycle and blockade of apoptosis increases the time required to repair the defects of a DNA. Antiapoptotic effects enhances survival chances at the early stage after irradiation in a particular range of doses. On the other hand, activation of apoptosis of altered cells can be seen as one of the mechanisms to delay aging processes and prevention of isolated effects of exposure to ionizing radiation. Formation of radiation-induced and age-related alterations are characterized by multiple factors and a variety of manifestations. Nevertheless, similarity of individual links of the pathogenesis of disease related to radiation exposure and aging of the body is striking. It could be stated that radiation-protective property defines an increase in life expectancy by short-term exposure in sub-lethal and lethal doses. However anti-aging activities prevent the development of remote effects of ionizing radiation by prolonged low doses or fractionated exposure to radiation.

[The impact of the COVID-19 epidemic on the elderly mental health and psychosocial support.]

The spread of the COVID-19 epidemic is accompanied by psychosocial problems that have negative consequences for the mental health (MH) and quality of life (QoL) of the majority of the population. The elderly (65+ individuals) with chronic somatic diseases and reduced adaptation reserves are particularly at risk. In General, the epidemic highlighted the growing problems of psychosocial work with the 65+ cohort in the conditions of progressive aging of the population of many developed and developing countries. These problems are directly related to the preservation of MH and QoL of elderly people, people with disabilities, and others. Additional reserves should be sought to support these categories of individuals. In particular, the use of remote tele-consulting and assistive information technologies that enhance the communication capabilities of older persons is relevant. The article analyzes publications that offer practical recommendations for reducing the negative effects of the COVID-19 pandemic on MH and QoL in a cohort of 65+ individuals. As a starting point of the discussion, the article by A.G.Golubev et al., in which the issues of public support for 65+ persons are considered to be the most relevant in the field of gerontology in the context of emergency response to the spread of the COVID-19 epidemic, is considered.

Mitigating Effect of Nitrates (Monizol) on Pharmacodynamic Shifts in the Cardiovascular System Caused by Radioprotector Indralin.

We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBA×C57Bl/6)F1 hybrids mice, and on blood loss from a wound on tip of the tail in mice. Being an α1-adrenomimetic, indralin caused hypertensive reaction with the development of bradycardia, reduced blood supply and spleen weight, and sharply reduced blood loss from the wound. Monizol as nitrate reduced BP without affecting HR and reduced blood loss from the wound. Monizol administered prior to indralin eliminated radioprotector-induced hypertensive reaction, reduced bradycardia by more than 2 times, and attenuated the effect of indralin on spleen weight and blood loss from the wound by 1.6-1.8 times. Monizol administered after indralin had no effect on shifts in peripheral blood supply caused by the radioprotector.

Pharmacological Analysis of the Therapeutic Effect of Radioprotectors Cystamine and Indralin in the Capacity of Radiomitigators.

The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body 60Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation. Moreover, summation of the radioprotective and therapeutic effects of the radioprotector was revealed under these conditions. In mice and rats, α1-adrenoreceptor blocker terazosin did not abolish the therapeutic effect of indralin administrated after irradiation, but blocked the radioprotective effect of indralin applied prior to irradiation. At the same time, 5-HT2 serotonin receptor blocker tropoxin abolished the therapeutic effect of indralin without affecting its radioprotective activity.

[Features of therapy for chronic pancreatitis associated with anxious depressive disorders in railway workers].

The article presents data on peculiarities of chronic pancreatitis course in railway transport workers (engine operators, engine operator assistants, dispatchers) with anxious depressive disorders. Pain and dyspepsia in patients with affective disorders appeared to be constant and more intense than in the patients without concomitant anxious depression. Psychophysiologic tests in 83% of patients with comorbid conditions revealed significant psychomotor dullness manifested in reliable lower speed of visual motor reactions. Pharmacologic correction via anxiolytics (Adaptol, Afobasol) combined with standard therapy for chronic pancreatitis exacerbation enabled to improve clinical symptoms, but Adaptol appeared to slow simple visual motor reactions, therefore has to be ruled out in engine operators. Pharmacotherapy of chronic pancreatitis, that included Afobasol in addition to standard treatment, promoted reliable improvement of occupationally important psychophysiologic functions. This study received a patent.

[SUBSTANTIATION OF DOSE LIMITS FOR A NEW NORMATIVE DOCUMENT ON RADIATION SAFETY OF LONG-DURATION SPACE MISSIONS AT ORBIT ALTITUDES OF UP TO 500 KM].

Review of the data of experimental radiobiology and epidemiological follow-up of large groups of people subjected to radiation exposures on Earth has been undertaken to substantiate dose limits for critical organs of cosmonauts in order to ensure good performance and vitality while on long-duration orbital missions. The career dose limits for cosmonauts and astronauts established earlier in the USSR and USA amounted to nothing more but banning the risk of cancer death increase to 3%. To apply more rigorous criteria of delayed radiation risks, the Russian limits for cosmonauts were revised to substantiate a 4-fold reduction of the average tissue equivalent dose maximum to 1 Sv. The total of cancer and non-cancer radiation risks over lifetime and probable reduction of mean life expectancy (MLE) were calculated using the model of radiation-induced mortality for mammals and taken as the main damage to health. The established dose limit is equal to the career dose for nuclear industry personnel set forth by Russian standard document NRB 99/2009. For better agreement of admissible threshold doses to critical human organs (bone marrow, lens and skin) in the revised radiation limits for long-duration space missions and radiation safety limits on Earth, reduction of dose limits for the critical organs were substantiated additionally; these limits comply with those for planned over-exposure on Earth in document NRB 99/2009.

Radioprotector indralin at early and late manifestations of local radiation injuries.

Experimental model of acute local radiation injuries (LRI) was the degree of radiation skin burns of mouse paws, observed through the 10 day within 1 month after local γ -60Co-irradiation at the doses of 20-45 Gy. For late local radiation injuries with a maximum of over 6 months after exposure to radiation, model was the contracture of animal paws and post-radiation amputation of limbs of the mouse. In the experiments on mice radioprotector indralin (B-190) IP as direct α1-adrenomimetic has a expressed protective effect on reducing acute and late LRI, equal in terms of dose reduction factor (DRF) 1.4 -1.5 that was comparable to their efficacy during radiation injuries of hematopoietic tissues. Indralin fully retain its radioprotective properties (DRF = 1.5-1.7) in the condition of repeated radioprotector administration through one day at total dose of 57 Gy (three times 19 Gy) of fractionated γ -irradiation. The protective effect of indralin improved at parenteral administration in the place of local irradiation. The local topical application of indralin in the ointments or in solution of dimethylsulfoxide has radioprotective effect, equal in the term of DRF to 1.3 -1.5 at acute and late LRI. Indralin also possessed a expressed radioprotective properties (DRF = 1.5) in decrease radiation injuries of salivary glands during local irradiation of head of rats.

Early Response of Mouse Bone Mrrow Cells to Short-Term Irradiation in a Wide Range of Doses.

Experiments on mice irradiated with γ-rays in a wide range of doses, from 0.5 to 400 cGy and the bone marrow have shown cytogenetic and cytological effects ranging from I cGy dose 24 hours after exposure to radiation. Dose-independent reduction of the number of nucleated cells in the bone marrow, normal or even elevated levels of mitotic activity, and extreme dependence of the type of chromosomal aberrations on the radiation dose with the maximum in the region of 7.5 cGy were observed in the dose range from 1 to 20 cGy. A linear dose-dependent decrease of the cell.number in the bone marrow, a decreased mitotic activity and increased number of aberrant mitosis were marked in the dose range from 20 to 400 cGy. The findings are discussed in terms of their application for explaining the mechanisms of hormesis, adaptive response, as well as the appropriateness of accounting the parameters studied for solving problems of regulation of permissible doses.

[DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE].

The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/µm to 1.6 keV/µm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect.

Radioprotective Properties of Indralin in Combination with Monizol in the Treatment of Local Acute and Delayed Radiation Injuries Caused by Local Skin γ-Irradiation.

Female rats were exposed to local γ-irradiation of the right hindpaw in doses of 30-50 Gy at 131-154 sGy/min dose rate. Radioprotector indralin was administered per os 15 min prior to irradiation, monizol was injected intraperitoneally 5 min after irradiation. Indralin showed marked radioprotective properties both for acute and delayed symptoms of local radiation injuries. In combination with monizol, radioprotective effect of indralin was potentiated to dose reduction factor of 1.4-1.5 both for radiation burn severity reduction and for restriction of postradiational contracture development and amputation of the irradiated limb.

Potential Role of Catecholamine Response to Acute Hypoxia in the Modification of the Effects of Radioprotectors.

Involvement of hormonal response (catecholamine release) to acute hypoxia induced by radioprotectors in modification of their radioprotective properties was studied in experiments on outbred mature female albino mice, female albino rats, and dogs of both sexes. The response intensity was evaluated by the reduction of radioprotective and toxic properties of indralin (a α1-adrenoceptor agonist and a radioprotector). The radioprotective effect of indralin was measured using lethal doses of whole-body γ-irradiation ((60)Co) and its acute toxicity was assessed by LD50. It was found that repeated administration of indralin with 30-60-min intervals was followed by weakening of its radioprotective effect. Similar sensitization effect of indralin was observed after pretreatment with cystamine and epinephrine. Comparison of the severity of sensitization after administration of epinephrine and cystamine in the dose providing radioprotective effect showed that the potential aminothiol-induced release of catecholamines can provide optimal long-term radioprotective effect of epinephrine.

[IMMEDIATE RADIOBIOLOGICAL EFFECTS IN MICE FOLLOWING γ-IRRADIATION BY LOW DOSES].

Outbred CD-1 mice females aged 4 to 4.5-months were investigated in 21-22 hours following total γ-irradiation at 10, 25, 50, 75, 100 and 200 mGy. Loss in bone marrow karyocytes, as well as spleen and thymus mass reductions were significant in the group of animals irradiated at 50 and 200 mGy and less dramatic in mice irradiated at 75 mGy. The orientative-trying behavior reaction (OTBR) in the open field tested in 19-20 hours after exposure to 10 and 25 mGy was reliably stronger than in the group of biological control; however, emotional status (ES) in the animals that received 10 mGy dropped significantly. Mice irradiated at 50 mGy were found to weaken the grip of their front limbs. Dose levels differing in opposite radiobiological effects on the parameters under study were established. Doses in the range from 10 to 25 mGy maximized OTBR and ES, while doses of 50, 100 and 200 mGy produced high reactions of the immune and hemopoietic organs.

[INVESTIGATION OF IRON, ZINC, STABLE STRONTIUM AND LITHIUM CONTENT IN BIOLOGICAL FLUIDS AND TISSUES DURING EXPERIMENTAL SPACE FLIGHT SIMULATION].

In an experiment with space flight simulation, atomic emission spectral analysis with inductively coupled argon plasma was employed to measure iron, zinc, stable strontium and lithium in blood serum and its ultrafiltered fraction, and excretion with daily urine and hair. Monitoring of serum iron and its ultraviolet fraction showed good balance of these parameters in all periods of the experiment. Blood serum was found to contain exclusively iron bound with protein carriers. In the experiment, serum zinc was distinctively dependent on the nutrient status. Stable strontium excretion with daily urine can be a biological indicator of its homeostasis. The experiment factors had no effect on the lithium form in serum, i.e. lithium was invariably present in the ionized form and in quantities equal to ultrafiltered lithium in all blood samples in all periods of the experiment.

[SQUALENE: PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES].

The review of literature demonstrates that squalene, known to most experts as an intermediate product in the synthesis of cholesterol, has several pharmacological properties including hypolipidemic, hepatoprotective, cardioprotective, antioxidant, and antitoxicant activity. Squalene is effective in the treatment of diabetes mellitus type 2 and can potentiate the activity of some antitumor (antiblastoma) preparations and reduce their undesired side effects. This bioactive substance has low toxicity and, in therapeutic doses, does not produce any damaging action on the human organism. A promising source of raw material for the commercial production of squalene is offered by amaranth seed oil.

[MODIFICATION OF THE PROTON BEAM PHYSICAL PARAMETERS AND RADIOBIOLOGICAL CHARACTERISTICS BY ELEMENTS OF SPACECRAFT RADIATION PROTECTION].

The experiment was performed with outbred ICR (CD-1). female mice (SPF). The animals were irradiated by 171 MeV protons at a dose of 20 cGy. The spacecraft radiation protection elements used in the experiment were a construction of wet hygiene wipes called a "protective blind", and a glass plate imitating an ISS window. Physical obstacles on the path of 171 MeV protons increase their linear energy transfer leading to the absorbed dose elevation and strengthening of the radiobiological effect. In the experiment, two types of obstacles together raised the absorbed dose from 20 to 23.2 cGy. Chemically different materials (glass and water in the wipes) were found to exert unequal modifying effects on physical and biological parameters of the proton-irradiated mice. There was a distinct dose-dependent reduction of bone marrow cellularity within the dose range from 20 cGy to 23.2 cGy in 24 hours after exposure. No modifying effect of the radiation protection elements on spontaneous motor activity was discovered when compared with entrance protons. The group of animals protected by the glass plate exhibited normal orientative-trying reactions and weakened grip with the forelimbs. Rationalization of physical methods of spacecrew protection should be based as on knowledge in physical dosimetry (ionizing chambers, thermoluminescent, track detectors etc.), so the radiobiological criteria established in experiments with animals.

[NEUROSEMANTIC AND PSYCHOPHYSIOLOGICAL CORRELATES OF RHYTHM-SUGGESTIVE CORRECTION OF STRESS CONDITIONS].

Correlates of successful rhythm-suggestive compensation of stress in sportsmen with neurotic symptoms developed in consequence of painful experience of failure were studied. Effectiveness of the rhythm-suggestive and rational psychological methods was compared by measuring the evoked potentials response to emotionally significant extramental verbal stimuli and images, and using psychophysiological test MASTER to track dynamics of a number of body functional parameters. The rational compensation has been shown to reduce the psychic tension and to set right the voluntary control process. Rhythm-suggestive programs are good for compensation of post-stress emotions and affectations, and the involuntary control process. It was found that correction potentialities of the rhythm-suggestive programs together with the psychodiagnostic advantages of test MASTER are promising instruments for dynamic monitoring of the mental state with the aim to prevent workplace stresses and to provide rehabilitation treatment of aftermaths.

[The BION-M1 project: overview and first results].

Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

[Unconscious components of the psychophysiological reactions of the participants in the experiment with 520-day isolation].

Six participants in MARS-500 were examined in an effort to gather information about intrapersonal conflicts and life spheres with high emotional tension associated with participation in the experiment with extended group isolation. The investigation was performed using the operational analogy-based neuro-semantic psychodiagnostics which allows to regard the subconscious as a semantic filter with unstructured semantic information at the input and information structured by the inner world content at the output. The results shed light on the semantic structure of subjective experience and functioning of protective mechanisms, as well as organizational levels and modality of emotional experience. Prior to and after 520-day isolation, all the participants were shown to have intrapersonal conflicts and high emotional tension in the socio-professional sphere, caused by the family/sexual and interpersonal relations and self-rating, and concerns about life and health. On the completion of isolation, the psychoemotional tension reduced quantitatively in interpersonal relations and increased in family/sexual.

Therapeutic effect of long-term melatonin treatment on the course and fatal outcome of modeled acute radiation sickness.

We studied the effect of long-term administration of melatonin to male C57Bl/6 mice starting from day 3 after whole-body γ-irradiation (9.5-10.0 Gy, 7.7-17.1 cGy/min). It was found that replacement of drinking water with melatonin solution (5 mg/liter) did not reduce the amount of fluid intake throughout the period of acute radiation injury. The daily dose of melatonin was 0.9-1.2 mg/kg body weight (this parameter was lower at the peak of the disease and increased during the recovery stage). Melatonin by more than 20% (p<0.05) improved survival of mice exposed to γ-irradiation in a dose of LD97/30, reduced leukopenia during the stage of acute manifestations of the disease and maximum mortality, and increased blood leukocyte count by 40% (p<0.05) by day 12 after irradiation.