Extreme Medicine

ISSN Print 2713-2757 ISSN Online 2713-2765

Extreme Medicine

SCIENTIFIC AND PRACTICAL REVIEWED JOURNAL OF FMBA OF RUSSIA

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Existing approaches to health risk assessment focus, primarily, on the comparative priority of pollutants and their sources in the environment. But these approaches cannot be used to predict real changes in the mortality or morbidity rates of the population living in a given territory, and therefore cannot be used to develop health-prevention measures aimed at preserving or restoring human health. In this regard, in this study it is (the author ?) proposed to use the concept of mitigation (in this context, actions aimed at reducing environmental pollution) and the concept of adaptation (actions aimed at reducing the vulnerability of populations to environmental pollution). The existing risk assessments can be used to develop mitigation measures, but are not much instrumental in development of adaptation measures, which need to concentrate on early diagnosis and prevention of diseases caused by environmental pollution, as well as on the development of rehabilitation measures. It has been noted that hygiene and epidemiological research has not paid enough attention to the differences between these areas of public chemical and radiation safety. Yet, better targeting when assessing the risk will help to more effectively design interventions to manage these risks.

Received: 2023-05-02

Published online: 2023-06-29

DOI: 10.47183/mes.2023.022

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VIEWS 1038

Bugaev-Makarovskiy NA, Ershov PV, Volkova AG, Makarova AS, Keskinov AA

Malignant neoplasms occupy a leading place among non-communicable diseases based on the number of patients and mortality rate. There are several fundamental approaches to cancer therapy, however, none of them are universal or show a high level of clinical response. Furthermore, all the approaches are characterized by a large number of adverse side effects. Today, immunotherapy used alone or in combination with other therapies is considered to be the most promising. Immunotherapy is usually the use of specific antibodies (immune checkpoint inhibitors) or special bioproducts, such as dendritic cells and artificially synthesized peptides, such as neoantigens . The review considers strategies for development of the dendritic cell- and neoantigen-based anticancer vaccines, the possibilities of their improvement and the efficacy of combining with other anticancer drugs. The summary of current clinical trials of the dendritic cell and neoantigen vaccines is provided along with a brief analysis of the basic strategies, achievements and challenges faced by the developers of such vaccines.

Received: 2023-05-10

Published online: 2023-06-28

DOI: 10.47183/mes.2023.019

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VIEWS 1030

Patrakeeva VP, Kontievskaya EV

The development of adaptive response to cold exposure is associated with the increased synthesis of the adrenal hormones involved in regulation of the immunocompetent cells’ functional and metabolic activity. Even people residing permanently in the North show different variants of response to cold. The study was aimed to determine the relationship between the baseline cortisol and adrenaline levels, as well as the changes in their concentrations associated with the adaptive immune response to whole body cooling. A total of 173 individuals were assessed before and after the short-term whole body cooling. White blood cell differential, cortisol, adrenaline and ferritin levels, and the presence of glycogen in lymphocytes were determined in peripheral blood. Three variants of response were defined: 1) the relatively low baseline levels of cortisol and adrenaline together with no increase in these levels after the cold exposure have no significant effect on the lymphocyte migration activity; 2) predominant activation of the sympathetic–adrenal–medullary axis is associated with lymphocyte mobilization into the bloodstream along with the decrease in their glycolytic activity; 3) the higher baseline levels of cortisol and further increase in its concentration until it reaches the upper limit of the normal range following cooling are associated with intensification of glycolisis in lymphocytes and the increase of lymphocyte migration to the tissues.

Received: 2023-05-10

Published online: 2023-06-26

DOI: 10.47183/mes.2023.020

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VIEWS 1251

Patrakeeva VP, Dobrodeeva LK

HL is characterized by significantly enlarged lymph nodes and the presence of rare Hodgkin and Reed-Sternberg cells. Pathogenesis is not fully understood. The increase in the disease risk can be associated with immunosuppression, HIV, parenchymal organ transplantation, autoimmune disorders, etc. The possibility of differentiating pathogenetic and protective immune responses associated with this disease will help understand the causes of the disease and the treatment prognosis. The study was aimed to determine the features of immune responses in HL depending on the disease duration and the circulating lymphocyte counts. A total of 134 patients with HL were assessed. The cytogram and phagocytosis were assessed in blood smears stained by the Wright-Giemsa procedure. The expression of lymphocyte markers in lymphocytes was determined using the indirect immunoperoxidase technique and flow cytometry. Serum levels of cytokines, immunoglobulins, autoantibodies and circulating immune complexes were assessed by enzyme immunoassay. Comparative analysis of the immune responses depending on peripheral blood leukocyte counts is provided. It has been found that prolonged HL course is associated with the decrease in the functionally active T cell counts, progressive neutropenia and monocytopenia, along with the increased activity of the reaginic reactions and autosensitization. In individuals with lymphocytopenia, mainly small lymphocytes die, the 3-fold decrease in the counts of such lymphocytes is observed; lymphocytopenia is associated with the deficiency of circulating T cells, both mature and immature, the concentrations of which decrease by 2.5–3 times, while B cell counts show no dramatic changes. The disease progression is associated with reduction of the lymphocyte homeostasis control by granulocytes and monocytes, along with progressive neutropenia and monocytopenia.

Received: 2023-04-07

Published online: 2023-06-21

DOI: 10.47183/mes.2023.018

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VIEWS 1156

Melikhova MV, Krasnov KA, Rozhko MA, Lapina NV, Krasnova AA

The existing non-cardiogenic pulmonary edema (NCPE) treatment methods are not sufficiently effective. N,N-Diethyl-5,5-diphenyl-2-pentynylamine hydrochloride (DDPA), the N-cholinolitic drug, is of interest as a potential remedy for treatment of toxic pulmonary edema (TPE). The study was aimed to determine therapeutic efficacy of the drug in animal TPE models. TPE in white rats was induced through intraperitoneal thiourea injection or nitrogen dioxide inhalation. Treatment of animals involved inhalation of the DDPA aqueous solution. The efficacy was estimated based on the animals’ survival rate and lung gravimetry data. The results were assessed based on descriptive statistics using the Student's t-test. In the model of thiourea-induced NCPE, the drug administered after the toxic exposure increased the animals’ survival rate and significantly decreased lung hydration levels (149% vs. 262.5% in non-treated animals). In the model of nitrogen dioxideinduced NCPE, the drug significantly increased the rats’ survival rate within the period between 0 and 5 h, however, the differences became non-significant within 24 h. The treated animals had 15–20% lower respiratory rate and pulmonary coefficients than non-treated animals 5 h after the NO2 exposure. The use of DDPA improved the survival rate and overall health in both TPE models, however, the thiourea-based model showed better treatment outcomes compared to the NO2–based model. Such differences can be explained by the deeper and more disruptive nature of the lung tissue injury caused by nitrogen dioxide compared to that caused by thiourea. Thus, the use of DDPA in individuals with injuries induced by pulmonotoxic chemicals may be promising at the prehospital stage.

Received: 2023-03-31

Published online: 2023-06-14

DOI: 10.47183/mes.2023.017

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VIEWS 1069

Vakunenkova OA, Ivnitsky JuJu, Gaykova ON, Kozlov AA, Schäfer TV

Myeloablative cytostatic therapy is often associated with gastrointestinal (GI) stasis that is a component of pathogenesis of the bacterial overgrowth syndrome, endotoxicosis, systemic inflammation, sepsis, emetic syndrome. The study was aimed to test the hypothesis that sodium bicarbonate (NaHCO3), the alkalinizing agent administrated by gavage in the rat model of myeloablative cytostatic therapy with cyclophosphamide (CP), would have a protective effect against GI stasis. We assessed the effects of intragastric NaHCO3 administrations on the development of GI stasis, acute chemotherapy-induced mucositis of the small intestine, and urinary excretion of indican using 140 Wistar rats with the body weight of 161–190 g as a model of myeloablative cytostatic therapy with the intravenously injected CP. The CP administration in a dose of 390 mg/kg resulted in dystrophic changes in the small intestinal mucosa, the development of GI stasis with predominant gastric stasis within the first 24 h, and the increase in excretion of indican. Intragastric administration of NaHCO3 in a dose equivalent to 350 mL of the 4% NaHCO3 solution in humans to rats 30 min before and immediately after the CP administration prevented acute chemotherapy-induced mucositis of the small intestine and alleviated the symptoms of gastric stasis and excessive growth of the indole-producing gastrointestinal microbiota. The reported approach to emergency drug prevention of the myeloablative cytostatic drug therapy gastrointestinal complications holds promise for testing of the use of CP and other alkylating drugs as cytostatic agents.

Received: 2023-04-06

Published online: 2023-06-12

DOI: 10.47183/mes.2023.016

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VIEWS 1107

For more than 60 years, residents of the villages on the Techa River have been chronically exposed to combined radiation, receiving a wide range of doses. Red bone marrow (RBM) is the critical system in the exposure conditions. This study aimed to assess the effect of chronic exposure on premature aging of T-lymphocytes based on the frequency of unstable chromosome aberrations; the subjects were the residents of the Southern Urals that have been chronically exposed to radiation. The increased frequency of occurrence of dicentrics and rings in T-cells of the exposed persons was the marker of cellular aging, with the associated doses to the red bone marrow (RBM dose) at 0.5–2.5 Gy. The participants (RBM donors), both exposed and non-exposed, were divided into three age subgroups: 40–59 years old, 60–69 years old, 70–79 years old. The differences in the RBM dose among the exposed individuals were insignificant. In the exposed group, unstable chromosome aberrations (UCA) were recorded significantly more often than in the control group (p = 0.04). The age group of 40–59 years was the one where the exposed donors had significantly more frequently occurring chromosome aberrations compared to the non-exposed participants. There were no such differences registered in other age groups. The age-associated increase of the amount of chromosome aberrations was registered in the non-exposed group only. Chronic exposure to radiation indirectly promotes premature aging of T-lymphocytes: 1) in the long term, the exposed individuals had UCA significantly more often; 2) compared to the control group, the 40–59 years age subgroup of the exposed group had increased cytogenetic index. In the context of this study, the number of dicentrics and rings was not registered as increasing in the older age subgroups of exposed individuals, which may be due to the specifics of the donor inclusion criteria, which, for the elderly, may favor radioresistant individuals.

Received: 2023-01-13

Published online: 2023-06-10

DOI: 10.47183/mes.2023.015

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VIEWS 1087

Pavlova AA, Klyuchnikov SO, Tarasova MS, Feshchenko VS, Zholinsky AV, Parastaev SA

Metabolic syndrome is one of the pre-nosological conditions that implies strain on several systems of the body and disruption of all types of metabolism. The key components of the syndrome are visceral obesity, peripheral tissue insulin resistance, arterial hypertension and non-alcoholic fatty liver disease. There is a number of diseases associated with the syndrome, which makes diagnosing its preclinical manifestations important. Overweight and obesity only continue spreading; moreover, these conditions are registered in people of increasingly younger age. Metabolic syndrome in childhood increases the risk of cardiovascular disease in adulthood. Top tier athletes are no exception. Some sports and playing roles promote body weight growth. A young athlete may have specific constitutional features, and, without proper control, motivating such athletes to grow muscles means they also grow fat. The recommendation is to pay special attention to children under the age of 11 that play rugby, American football as line men, in heavy weight categories. Application of the latest diagnostic criteria with their actualization on a regular basis, as well as search for additional markers and parameters identifiable in laboratory settings, would ensure adjustment of the athlete's condition in a timely manner.

Received: 2023-04-05

Published online: 2023-06-09

DOI: 10.47183/mes.2023.014

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VIEWS 1083