No 6 (2022)

Вот и заканчивается 2022 год! Год был отмечен как новыми свершениями, так и горькими потерями. Мы потеряли двух членов редколлегии — выдающихся советских, российских учёных, замечательных людей Т.А. Гуськову и Б.А. Кацнельсона. Светлая им память!

Жизнь не стоит на месте! Сегодня редколлегия пополнилась новыми членами: доктором медицинских наук, директором ФБУН «Екатеринбургский медицинский центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, ученицей Б.А. Кацнельсона М.П. Сутунковой, а также нашей коллегой, высокопрофессиональным учёным, заведующей лабораторией токсикологии Республиканского унитарного предприятия «Научно-практический центр гигиены» Минздрава Республики Беларусь, кандидатом медицинских наук И.И. Ильюковой.

Сегодня, когда пересмотрены критерии рейтингов журнала, «Токсикологический вестник» входит в К2. Нам есть к чему стремиться, есть понимание, как развиваться!

В канун Нового 2023 года разрешите поздравить вас с замечательным праздником, пожелать здоровья вам и вашим близким, счастья, новых свершений, мира и добра!

Главный редактор Х.Х. Хамидулина

Introduction. Traditionally, the hygienic assessment of working conditions when using glyphosate preparations, an extremely popular herbicide in the world, is based on the use of thin layer chromatography. In this paper, alternative approaches are considered. On the basis of experimental data, the conditions for the analysis of glyphosate content in air by high performance liquid chromatography were optimized.

Materials and methods. All work with glyphosate solutions was carried out in polypropylene vessels. Sampling from the air medium was carried out on a medium filtration filter (“blue ribbon”). Subsequent extraction was carried out with water. The measurements were performed by high performance liquid chromatography with a fluorescence detector at an excitation wavelength of 270 nm and an emission wavelength of 313 nm. To transfer glyphosate to a molecule with fluorimetric properties after derivatization of glyphosate in an alkaline medium using 9-fluorenylmethyl chloroformate by heating and washing off the excess of the reagent with toluene. A C18 reverse phase column was used; ammonium acetate with the addition of acetic acid and acetonitrile were used as eluents.

Results. Approbation of the developed technique was carried out on real samples taken during ground treatment of fallow fields and lands of industrial territories with glyphosate preparations. The detected levels of glyphosate did not exceed the lower limit of quantitative determination: 0.5 mg/m3 in the air of the working area and 0.025 mg/m3 in the atmospheric air (with maximum allowable concentrations of 1.0 and 0.1 mg/m3, respectively).

Conclusion. Based on the results of the work performed, methodological instructions "Measurement of glyphosate concentrations in the air by high-performance liquid chromatography" were formed and sent for metrological certification in the approved manner.

Резюме

Введение. Car-T-клеточная терапия является современным перспективным методом в лечении онкологических заболеваний. На сегодняшний день управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США одобрено только два препарата для клеточной иммунотерапии онкологических заболеваний крови. Однако отсутствует информация о доклинических испытаниях данных биомедицинских клеточных продуктов, так как используемые в них Т-клетки, несущие химерный антигенный рецептор, являются аутологичными для человека, что представляет проблему для применения к ним классических токсикологических тестов. Кроме того, это ставит под сомнение безопасность данных лекарственных средств, поэтому разрабатываются различные стратегии доклинических исследований, которые позволили бы преодолеть вышеуказанные проблемы и создать адекватные тест-системы с терапевтической мишенью.

Цель исследования - оценка острой токсичности противоопухолевого препарата на основе генетически модифицированных T/NK-клеток, экспрессирующих химерный Т-клеточный рецептор против антигена HER2, на иммунодефицитных мышах линии BALB/c Nude.

Материалы и методы. Опытная и контрольная группы включали 5 самцов и 5 самок. Тестируемый препарат, а также носитель (растворитель-криоконсервант) животным вводили однократно внутривенно или внутрибрюшинно, в объеме 0,2 мл/животное. Опытным животным исследуемый препарат вводили в двух дозах: 0,5х10⁶ клеток/животное, эквипотенциальной терапевтической дозе для человека, и 5 х10⁶ клеток/животное, в 10 раз превышающей терапевтическую дозу. В ходе исследования у животных регистрировали вес тела, потребление корма и проявление клинических признаков токсичности исследуемого препарата. На 15-й день исследования животные были подвергнуты эвтаназии и некропсии с осмотром макроповреждений органов, их взвешиванием и фиксацией. С целью выявления токсического действия тестируемого биомедицинского клеточного продукта проводили гистологический анализ.

Результаты. Установлено, что однократное внутривенное или внутрибрюшинное введение биомедицинского продукта «анти-HER2-CAR-T/CAR-NK» в дозе, эквивалентной терапевтической для человека, является безопасным для мышей BALB/c Nude.

Заключение. Данная работа может стать основой для создания протокола по доклиническим испытаниям биомедицинских клеточных продуктов, полученных с помощью CAR- технологий.

Introduction. Acute exposure to chemicals is the most common cause of poisoning in pediatric practice and one of the leading causes of morbidity and mortality worldwide [1]. In the available domestic literature, we have not found publications concerning up-to-date data on the etiological structure, clinical characteristics of patients and outcomes of acute poisoning in children. Knowledge of clinical manifestations and prognosis for various poisoning in children will help doctors of the outpatient level and the reception department of hospitals to quickly determine the tactics of patient management and prevent serious consequences.

Material and methods. In this retrospective study, the case histories of 300 children aged 0 to 18 years who were admitted to the emergency department of the third — level hospital — the Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan with acute poisoning for the period from 2018 to 2020 were studied.

Results. The study included 176 boys (58.6%) and 124 girls (41.4%). Poisoning was most common in the age periods from 1 to 3 years — 127 (42.3%) and from 12 to 18 years — 76 (25.3%). 67% of poisoning were unintentional, and in 33% of cases — intentional. The largest number of poisonings — 248 (82.7%) occurred at home, and 52 (17.3%) were poisoned outside the home. Of the 300 cases of poisoning, 70 (23.3%) were of mild severity, 151 (50.3%) of moderate severity, 79 (26.3%) of severe severity. The most common toxic substances were: chemical detergents, carbon monoxide, vasoconstrictor drugs, nonsteroidal anti-inflammatory drugs. All 300 patients survived.

Limitations of the study. The data of patients living in the Republic of Tatarstan who were admitted to the emergency department of the DRKB for the time period from 2018 to 2020 were studied.

Conclusion. Over the past 2 years, there has been an increase in the frequency of poisoning in the city of Kazan. Most patients had mild to moderate poisoning, more often unintentional. A serious condition was observed in adolescents when the cause of poisoning was a suicide attempt. The increase in the number of poisonings can be associated with the over-the-counter sale of a large number of drugs, their aggressive advertising, as well as improper storage at home.

Compliance with ethical standards: the study does not require the submission of the conclusion of the biomedical ethics committee.

Contribution of the authors: all co-authors made an equal contribution to the research and preparation of the article for publication. 

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

Funding. The study had no sponsorship.

Received: February 14, 2022 / Accepted: December 12, 2022 / Published: December 30, 2022

Introduction. The prevalence of rhabdomyolysis among people admitted to the hospital due to acute poisoning reaches, according to various foreign sources, from 30 to 40%. In 60% of cases, the development of rhabdomyolysis in adult patients is associated with acute exogenous intoxication. Currently, data on the prevalence, structure and outcomes of treatment of rhabdomyolysis in toxicological patients are mainly presented by the results of foreign clinical and epidemiological studies.

The aim is to study the prevalence, structure, frequency of complications and outcomes of treatment of rhabdomyolysis in acute exogenous intoxication in a multidisciplinary hospital.

Material and methods. The study included 1,363 patients who were treated from 2017 to 2020 with acute exogenous intoxication. During the study, 98 patients with rhabdomyolysis were selected from the general group. The frequency of poisoning with various toxicants was analyzed, the effects of which led to the development of rhabdomyolysis in acute exogenous intoxication. The incidence of acute kidney injury (AKI) was detected, the outcomes of acute poisoning treatment, the duration of inpatient treatment were determined, and a comparative analysis was carried out between groups of patients with rhabdomyolysis in acute exogenous intoxication (n=98) and without it (n=1265).

Results. The prevalence of rhabdomyolysis among patients hospitalized for acute poisoning was 7%. The main reason for the development of rhabdomyolysis was the use of narcotic drugs — 87% of cases. The development of rhabdomyolysis in acute exogenous intoxication in 59.2% of cases is accompanied by the occurrence of AKI, which is significantly higher than among patients without rhabdomyolysis (11.6%). The occurrence of rhabdomyolysis in toxicological patients increases hospital mortality from 6.1 to 10.2%, as well as the duration of inpatient treatment and intensive care by 5.2 and 3.3 days, respectively.

Limitations. The study was conducted based on only one multidisciplinary hospital in Moscow in the period from 2017 to 2020.

Conclusion. Rhabdomyolysis is a serious complication of acute poisoning, the development of which significantly worsens the outcomes of treatment of patients with a toxicological profile, which requires the development of effective methods for the prevention, diagnosis and treatment of rhabdomyolysis in acute exogenous intoxication.

Compliance with ethical standards. The study does not require the submission of the conclusion of the biomedical ethics committee.

Author contribution:
Masolitin S.V. — concept and design of the study, collection and processing of material, statistical analysis, writing the text of the article;
Kim V.G., Magomedov M.A. — collection and processing of material;
Marukhov A.V., Chubchenko N.V. — statistical analysis, editing the text of the article;
Protsenko D.N., Tyurin I.N., Mamontova O.A. — editing the text of the article.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

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

Funding. The study was not sponsored.

Received: February 28, 2022 / Accepted: December 12, 2022 / Published: December 30, 2022

Introduction. Occupational contact with selenium and its compounds, including nanoscale forms, occurs in the glass production, rubber industry, metallurgy (metallurgical processes of copper sludge processing, copper pyrite roasting, manganese, selenium and tellurium production). There are scarce data on the toxicity of selenium nanoparticles.

Material and methods. Stable suspensions of nanoparticles or deionized water (control group) were administered to male rats 3 times a week for 6 weeks. A single dose of selenium oxide nanoparticles was 0.2 or 1 or 2 mg/kg of body weight). The condition of the animal organism was assessed with a number of indicators of toxic action at the end of the experiment. The statistical significance of intergroup differences was assessed by Student's t-test.

Results. Activity of succinate dehydrogenase in blood lymphocytes reflecting the intensity of energy processes in the organism was decreased. The number of eosinophils in smears-imprints of parenchymal organs and mesenteric lymph nodes increased, indicating the ability of selenium nanooxide to trigger signaling cascades in immunocompetent cells. The number of degenerated cells in the proximal and distal tubules in smears of the kidneys was increased. A tendency to a decrease in all hemodynamics parameters was found. A change in the QT duration, together with an increase in the amplitude of the T wave, probably indicates a violation of the processes of myocardial repolarization. The coefficient of fragmentation of genomic DNA in nucleated blood cells decreased.

Limitations. The research was limited to the study of indicators of toxic action in only one study using a limited dose range.

Conclusion. An ambiguous effect of selenium oxide nanoparticles on rats was found. Along with negative impact of nanoparticles we have demonstrated, for the first time, some beneficial outcomes, in particular, genome-protective action which is in a striking contrast with the genotoxicity of all elemental and element-oxide nanoparticles previously studied in our laboratory.

Compliance with ethical standards. The study was carried out in accordance with the "International guiding principles for biomedical research involving animals" (the Council for International Organizations of Medical Sciences, the International Council For Laboratory Animal Science, 2012). The work was approved by the Local Independent Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers is a Research Institute of Rospotrebnadzor.

Author contribution:
Katsnelson B.A., Sutunkova M.P., Minigalieva I.A., Privalova L.I., Ryabova Yu.V. — the concept and design of the study;
Klinova S.V., Ryabova Yu.V., Tazhigulova A.V. — conducting experiments;
Sakhautdinova R.R., Klinova S.V., Ryabova Yu.V., Bushueva T.V., Makeyev O.G., Tazhigulova A.V. — data obtaining and processing.
All co-authors — discussing the draft paper, editing, and approving the final version of the article.

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

Funding. Funded by the budget of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Received: February 2, 2022 / Accepted: December 12, 2022 / Published: December 30, 2022

Цель исследования − обобщить многолетний опыт авторов по диагностике и лечению острых отравлений производными барбитуровой кислоты и представить результаты детального исследования клиники барбитуровой интоксикации, которые доказывают токсическое повреждающее действие на организм, вызывающее глубокое торможение функций центральной нервной системы (ЦНС) с преимущественным воздействием на кору и вегетативные центры ствола головного мозга.

Материалы и методы исследования. Проведен анализ 385 пациентов с острыми отравлениями барбитуратами разной степенью тяжести, находившихся на лечении в отделении неотложной токсикологии НИИ СП им Н.В.Склифосовского. Оценена клинико-энцефалографическая картина острого отравления. Рассмотрены и проанализированы данные ЭЭГ двух групп больных, с возможностью определения типа биоэлектрической активности мозга. Информативное значение этих типов ЭЭГ для врача заключается в сопоставлении с особенностями клинических и токсикологических данных.

Результаты и обсуждения. Обобщая полученные результаты клинико-электроэнцефалографических изменений при отравлениях барбитуратами, отмечено, что выделенные типы биоэлектрической активности мозга, соответствуют определенной клинической симптоматике, и свидетельствуют о различной степени тяжести отравления. Это даёт возможность практикующему врачу после записи ЭЭГ у больного, находящегося в коматозном состоянии, предварительно поставить диагноз острого отравления барбитуратами, целенаправленно проводить токсикологическое исследование и до получения анализа начать проведение специфического лечения.

Аналептик бемегрид вызывает прямое стимулирующее влияние на ЦНС.  При введении небольших доз бемегрида отмечалась умеренная активация биоэлектрической активности головного мозга.

Наш опыт лечения больных с данным отравлением показал отрицательное воздействие больших доз бемегрида на ЦНС, что может привести к тормозящей фазе парабиотического торможения (по Н.Е. Введенскому).

Introduction. Traditionally, the hygienic assessment of working conditions when using glyphosate preparations, an extremely popular herbicide in the world, is based on the use of thin layer chromatography. In this paper, alternative approaches are considered. On the basis of experimental data, the conditions for the analysis of glyphosate content in air by high performance liquid chromatography were optimized.

Material and methods. All work with glyphosate solutions was carried out in polypropylene vessels. Sampling from the air medium was carried out on a medium filtration filter (“blue ribbon”). Subsequent extraction was carried out with water. The measurements were performed by high performance liquid chromatography with a fluorimetric detector at an excitation wavelength of 270 nm and an emission wavelength of 313 nm. To transfer glyphosate to a molecule with fluorimetric properties after derivatization of glyphosate in an alkaline medium using 9-fluorenylmethyl chloroformate by heating and washing off the excess of the reagent with toluene. A C18 reverse phase column was used; ammonium acetate with the addition of acetic acid and acetonitrile were used as eluents.

Results. Approbation of the developed technique was carried out on real samples taken during ground treatment of fallow fields and lands of industrial territories with glyphosate preparations. The detected levels of glyphosate did not exceed the lower limit of quantitative determination: 0.5 mg/m³ in the air of the working area and 0.025 mg/m³ in the atmospheric air (with maximum allowable concentrations of 1.0 and 0.1 mg/m³, respectively).

Limitations. The study considers a limited number of chromatographic columns. The study is performed on 25 model samples of the air of the working area and atmospheric air.

Conclusion. Based on the results of the work performed, methodological instructions “Measurement of glyphosate concentrations in the air by high-performance liquid chromatography” were formed and sent for metrological certification in the approved manner.

Compliance with ethical standards: no provision of the conclusion of the Biomedical Ethics Committee or other documents is required.

Author contribution:
Fedorova N.E., Dobrev S.D. — the concept and design of the study;
Stepanova N.A. — collection and processing of the material, statistical analysis;
Ivchenkova A.A. — collection and processing of the material, statistical analysis, writing the text, editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

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

Funding. The study had no sponsorship.

Received: April 15, 2022 / Accepted: December 12, 2022 / Published: December 30, 2022

24 декабря 2022 г. отмечает свой юбилей Хамидулина Халидя Хизбулаевна. Родилась в г. Москве. После окончания Первого Московского медицинского института им. И.М. Сеченова была распределена на кафедру гигиены труда, где в 1988 г. защитила диссертацию на соискание учёной степени кандидата медицинских наук по теме «Вопросы гигиены труда и промышленной токсикологии при работе с соединениями рубидия».