


No 5 (2023)
- Year: 2023
- Published: 13.11.2023
- Articles: 7
- URL: https://rjsocmed.com/0869-7922/issue/view/9771
- DOI: https://doi.org/10.47470/0869-7922-2023-31-5
Original articles
Intestinal lavage for intravenous methadone poisoning
Abstract
Introduction. Among opioid poisonings, acute intravenous methadone poisoning is distinguished by the most severe course with a pronounced manifestation of toxic-hypoxic encephalopathy, a large number of complications, deposition in tissues, which complicates its removal from the body and requires the greatest resource costs during the treatment process.
The aim of the study. To increase the effectiveness of treatment of patients with intravenous methadone poisoning by including intestinal lavage in the complex of standard therapy.
Material and methods. Of the 52 patients with intravenous methadone poisoning, 33 (observation group) underwent intestinal lavage (IL) for the purpose of detoxification, and 19 received standard therapy (comparison group). The age of the patients was 32.0 (29.0; 36.0), and in the comparison group — 31.0 (25.0; 37.0) years. Poisoning occurred as a result of the use of methadone when administered intravenously for the purpose of drug intoxication, which resulted in depression of consciousness (coma) and rare inadequate breathing with periods of apnea. IL was started urgently after restoration of adequate breathing. To carry out IL, enteral solution (ER) was administered through a nasogastric tube at a rate of 1950–2600 ml/hour. Perfusion of the gastrointestinal tract (GIT) was stopped when clear lavage water appeared from the rectum. The total volume of the solution was 7.0 (4.5; 7.5) l, the volume of intestinal secretions was 5.3 (4.0; 6.3) l, the duration of the procedure was 4 (3; 6) hours. The quantitative content of methadone in blood and urine, as well as in washing waters, was determined by gas chromatography with mass-selective detection.
The duration of coma, length of hospitalization, incidence of pneumonia as a complication of poisoning, and mortality in the observed and comparison groups were compared.
Results. With the help of IL, cleansing of the gastrointestinal tract of patients occurred within 3–6 hours. Methadone was detected in the washing waters, and its concentration in the blood after IL decreased by an average of 2.5 times. 19 (16.0; 27.0) hours after IL, the patients were in clear consciousness, which was 13 hours (40.6%) earlier than in the comparison group, in which it took an average of 32.0 hours to restore clear consciousness (24.5; 35.0) h (p < 0.05). Pneumonia in the group of patients who underwent IL occurred 2.6 times less frequently than in the comparison group. The duration of stay of patients in the intensive care unit of the observed group was 2.6 times shorter than in the comparison group, and the total length of hospitalization was 1.5 times less, respectively. There were no deaths in the observed group, and in the comparison group the mortality rate was 5.3%.
Limitations. The study concerns the effectiveness of intestinal lavage as a detoxification method for acute intravenous methadone poisoning in male and female victims, the limitations of which were: nosological form, period of poisoning, age of patients (from 18 to 65 years) and the absence of positional compression syndrome.
Conclusion. The use of IL in intravenous methadone poisoning promotes the elimination of the latter from the gastrointestinal tract, which is accompanied by a decrease in its concentration in the blood, a reduction in the duration of coma, a decrease in the incidence of pneumonia and mortality.
Compliance with ethical standards. The study was approved by the local Ethics Committee of the State Budgetary Healthcare Institution “Research Institute for Emergency Medicine named after N.V. Sklifosovsky” of the Moscow City Health Department. Protocol No. 5–21 dated 05/25/2021. The studies were conducted in compliance with the requirements of confidentiality of personal data, ethical standards and principles of conducting medical research with human participation, set out in the Helsinki Declaration of the World Medical Association.
Author contribution:
Tkeshelashvili T.T., Matkevich V.A. — concept and design of the study, writing text, editing;
Potskhveriya M.M. — concept and design of the study;
Tyurin I.A. — organization and implementation of chemical-toxicological research, analysis of the data obtained.
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: June 23, 2023 / Accepted: October 19, 2023 / Published: October 30, 2023



Study of the anticonvulsant activity of the original valproic acid amino ester in various models of convulsive syndrome
Abstract
Introduction. Despite a significant number of antidotes (atropine, pyridoxine) and anti-seizure drugs in clinical practice (benzodiazepines, barbiturates, valproates, anesthetics), the development of new antidotes for the relief of refractory seizures and recurrence of convulsive syndrome is actual problem.
The aim of the work was to study the specific pharmacological activity of a new original derivative of valproic acid in an experiment on models of convulsive syndrome with different mechanisms of action.
Material and methods. A comparative study of the effectiveness of the original substance ((1-methylpiperidin-4-yl)-2-propylpentanoate hydrochloride, VAA) was carried out on electroshock, GABA-lytic, catecholamine-dependent seizure models in rats and mice.
Results. A significant decrease in seizure activity was revealed in the group with prophylactic administration of VAA in the dose range of 11, 27 and 65 mg/kg in comparison with the control group received only phenylcarbamate. In an intergroup comparison, a low dose (11 mg/kg) more than others had an effect on the latent period of the onset of phenylcarbamate seizures, an average dose (27 mg/kg) reduced the duration of the seizure period, a high dose (65 mg/kg) affected the severity of convulsions, while the integral indicator (convulsive activity) did not differ between the medium and high dose subgroups. There was no significant decrease in seizure activity in models with the use of corazol, camphor, and the model of maximum electric shock.
Limitations. Testing of new pharmaceutical substances (study of efficacy and safety) should be carried out on laboratory animals before confirmation of efficacy in humans. The quantity of animals was limited by the need to comply with bioethical principles and sufficient number for statistically significant results and amounted 6 individuals in each group.
Conclusion. The release of valproic acid during the metabolism of VAA is slow and its concentration is insufficient to realize the universal anticonvulsant activity of VAA. It is necessary to further study the effect on cognitive functions and neuroprotective properties. Since antidote efficacy superior to atropine has been previously demonstrated, VAA is recommended for development as an antidote for organophosphorus poisoning.
Compliance with ethical standards. The experiment with animals was approved by the bioethical commission of the Golikov Research Center of Toxicology.
Author contributions:
Melekhova A.S. — conducting scientific research (experiments on animals), material processing, text writing;
Melnikova M.V., Belskaya A.V., Bondarenko A.A. — conducting scientific research (experiments on animals);
Bespalov A.Ya. — development and synthesis of vlproic acid amino ester for experiments;
Zorina V.N. — material processing, text writing;
Shustov E.B. — scientific guidance during research, 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 work was carried out according to the research plan within the framework of a state assignment.
Received: June 22, 2023 / Accepted: October 19, 2023 / Published: October 30, 2023



Impact of seasonality on certain parameters of behavioral testing in rats
Abstract
Introduction. Effects of the daytime period (circadian photoperiod) and seasonality on behavioral reactions and physiology of humans and animals remains one of the important issues of modern science.
Material and methods. We have summarized our own data on control animals collected in experimental studies conducted in all seasons of the year. The hole-board test and summation threshold index were chosen to assess the behavior of rats. The data analysis was performed in Microsoft Excel 2016 using Student’s t-test, p<0.05. In addition, we estimated a percent deviation of the indicators under study from their annual averages.
Results. We established that, as assessed by the number of head dips in the hole-board test, male rats kept at natural lighting demonstrated the most active exploratory behavior in spring and autumn while in summer, on the opposite, their exploration was statistically reduced. Values of the summation threshold index were the highest in winter and summer but lower in spring and especially in autumn. In springtime, the summation threshold index in male rats was statistically different from that observed in autumn and winter. In female rats, the index of the the hole-board test in spring was statistically significantly increased compared to data for all seasons of the year.
Limitations of the study. An analysis was carried out of the data obtained at the experimental animal clinic of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers for 7 years (2015–2022).
Conclusion. Our findings show that duration of the daytime period and seasonality can affect the results of some behavioral tests measuring lability of the central nervous system and exploratory activity of animals. They can contribute to the methodological basis for planning toxicity testing with account for seasonal fluctuations in physiological parameters of laboratory rodents.
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 Federal Budgetary Institution «Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers» of Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing. protocol No. 2 of 04/20/2021.
Contribution of the authors:
Minigalieva I.A., Shabardina L.V., Ryabova Yu.V., Butakova I.V. — study conception and design, writing text;
Solovyeva S.N. — study conception and design, conducting an experiment, collection and processing of the material, writing text;
Sutunkova M.P., Privalova L.I. — study conception and design;
Klinova S.V. — study conception and design, conducting an experiment, collection and processing of the material;
Romanova K.V. — conducting an experiment, collection and processing of the material.
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: May 25, 2023 / Accepted: October 19, 2023 / Published: October 30, 2023



Ecological Toxicology
Influence of forest fire smoke on the decline of biodiversity and the state of living organisms (literary review)
Abstract
Introduction. The relevance of this work is due to the growing environmental problem associated with large-scale forest fires and insufficient knowledge of the survival, adaptation and reproduction of animals after prolonged exposure to harmful smoke components.
The aim of the review is to collect and analyze information on environmental pollution due to smoke from forest fires and their impact on animals in the smoke zone.
Material and methods. The material for the analysis was the literature sources published for the period up to 2022, in publications indexed in the Scopus, Web of Science, Publons, Springer, PubMed databases, including domestic and foreign research scientists on this topic.
Results. When forest fires occur, a mixture of gaseous compounds is released into the environment, containing ultrafine solid particles, carbon monoxide, ozone, polycyclic aromatic hydrocarbons, nitrogen and sulfur dioxide, aldehydes, chlorinated dioxins, free radicals and many other compounds. At the same time, significant damage is caused to a wide biodiversity of the animal world, which is an extremely important indicator link in almost any biocenosis.
Conclusions. The increase in large-scale smoke is increasingly leading to the risk of extinction of wildlife exposed to high concentrations of toxic components of smoke. It is necessary to constantly maintain and restore the biotic potential of populations of endangered species in forest ecosystems, as well as a deeper study of the mechanisms of the occurrence of consequences that are dangerous for the animal organism when exposed to forest fire smoke.
Contribution of the authors:
Andreeva E.S. — concept and design of the study, writing text, editing;
Vokina V.A. — collection and processing of the material, writing text.
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 work was carried out according to the plan of research work within the framework of the state assignment.
Received: June 26, 2023 / Accepted: October 19, 2023 / Published: October 30, 2023



Evaluation the toxic effect of copper ions on the condition indices of benthic diatom Actinocyclus subtilis (W.Gregory) Ralfs 1861 in the experiment
Abstract
Introduction. Pollution of marine coastal areas lead to the relevance of environmental monitoring including application of biotesting methods based on- the cultures of unicellular algae. Microalgae have different species-specific resistance to pollutants that expands application of different species as bioindicators of marine pollution.
The aim of the study was to determine the threshold concentration of copper ions (Cu2+) for the survival and increase in the cells number of benthic diatom Actinocyclus subtilis (W.Gregory) Ralfs 1861 (Bacillariophyta) under the wide range of toxicant concentrations during 10-day toxicological experiments.
Material and methods. The response of strain culture of the benthic diatom A. subtilis to various concentrations of copper sulfate (ranged from 16 to 1024 μg/l in terms of Cu2+ ions) was studied. In accordance with the previously developed protocol, the following indices were evaluated: alterations in the absolute number and proportion (%) of alive cells in the test-culture, as well as the specific growth rate in the number of A. subtilis cells at different concentrations of toxicant. Counting of alive and dead cells was carried out by micrographs taken for 12–15 random viewing fields under Nikon Eclipse inverted light microscope.
Results. It was found that in the control and at concentration of copper ions 16 μg/l, the increase in the absolute number of cells in culture is described by sigmoid response curve. At the control еhe exponential growth phase occurs on days 5–7 and at concentration of 16 µg/l on days 3–5 of the experiment. The threshold concentration of copper ions (32 μg/l) which is critical for the survival of A. subtilis was determined, which is 3–7 times lower than threshold level for other benthic diatom species. At concentration of 32 µg/l, the phases of acceleration and exponential growth on the abundance curve are absent. The proportion of living cells in the culture decreases to 80% of the control level on day 3 and to 39% by day 10. At Cu2+ concentrations of 64 µg/l and above, sharp inhibition and death of culture is observed as early as 1–3 days. A positive specific growth rate of A. subtilis culture was revealed in the period of 1–5 days at copper concentration of 16 and 32 µg/l, and at concentration of 64 µg/l and higher the culture dies off. Negative values of the specific growth rate for all concentrations of the toxicant within the period of 5–10 days were obtained.
Limitations. By the results of 10-day experiments the effect of 8 concentrations of copper sulfate on the culture of marine benthic diatom A. subtilis was studied. Three replicates in each concentration and exposure time were measured (1350 measurements in total), which is sufficient sampling for statistically reliable determination of the threshold values of copper ion toxicity for given test object.
Conclusion. Considering the results obtained, the benthic diatom A. subtilis is highly sensitive to copper ions impact and can be recommended as new test-object for toxicology, as well as for application in monitoring of marine water areas subject to technogenic pollution.
Compliance with ethical standards. The study does not require the decision of biomedical ethics committee or other documents, since all experiments were carried out on common unicellular non-toxic algae, which does not violate any prohibitions associated with damage to the ecological environment, the living space of bio-communities, and also does not lead to irreversible changes in the biological (genetic) nature and human health.
Contribution of the authors. All authors confirm that their authorship complies with the international ICMJE criteria (all authors made a significant contribution to the development of concept, research and preparation of the article, read and approved its final version before publication).
Gratitude. The authors express their gratitude to S.A. Trofimov and Yu.I. Litvin for their help in maintaining clone cultures and conducting experiments, as well as to V.N. Lishaev for microphotography on the Hitachi SU3500 SEM.
Conflict of interests. The authors declare no conflict of interests.
Acknowledgements. This study was carried out as a part of the State Assignment No. 121030100028-02 of the A.O. Kovalevsky Institute of Biology of the Southern Seas of RAS in Benthos Ecology Dept.
Received: June 9, 2023 / Accepted: October 19, 2023 / Published: October 30, 2023



Research methods
New approaches to the determination of organochlorine pesticides in food products and food raw materials
Abstract
Introduction. The current methods for determining the residual amounts of organochlorine pesticides – 4,4-dichlorodiphenyltrichloromethylmethane (DDT) and its metabolites, hexachlorocyclohexane (HCH) (α, β, γ isomers) in food products and food raw materials, subject to mandatory declaration for their content, despite a fairly high sensitivity, are characterized by low measurement selectivity and are based on the use of obsolete equipment, time-consuming sample preparation.
Material and methods. In the work, the method of gas chromatography with mass spectrometric detection on a gas chromatograph “Khromatek-Kristall 5000.2” was used. Sample preparation was carried out by the method of matrix solid-phase dispersion, based on the destruction and dispersion of the analysed sample together with florisil in order to obtain a free-flowing dry mixture.
Results. The effectiveness of the method has been proven by validation on 16 model samples of food products of animal origin of various compositions. The versatility of the analysis procedure is ensured by the systematization of food products according to their structural and mechanical properties into groups: liquid, having a finely dispersed structure and a high water content (group A); viscous and pasty products having a fine structure (group B); products of animal origin requiring grinding and dispersion (semi-solid and solid), having a high water and/or fat content, not free-flowing (Group B); dry products of animal origin (dried or freeze-dried), and/or free-flowing powdered products with a low water content that require wetting, grinding and dispersion (Group D). Ingredient composition (water, fat, protein, hydrocarbons) does not significantly affect the stability and reproducibility of the developed method.
Limitations. The method has been tested and validated on samples of food products of animal origin.
Conclusion. The developed method for the determination of DDT and its metabolites, HCH (isomers α, β, γ), providing a range of measured concentrations (0.01–1.0 mg/kg) will make it possible to control the content of substances in all groups of food products of animal origin identified in the TR CU 021/11 “On food safety”, including products for baby food.
Compliance with ethical standards. The study does not require the submission of a Biomedical Ethics Committee conclusion or other documents.
Contribution:
Fedorova N.E. — concept and design of the study, writing the text;
Dobreva N.I. — concept and design of the study, collection and processing of material, collection of literature data, writing the text;
Bondareva L.G. — concept and design of the study, collection of literature data, editing;
Suslova A.V. — collection and processing of material, statistical processing of the material.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Funding. The study doesn’t have any sponsorship.
Conflict of interests. Authors declare no conflict of interests.
Received: September 5, 2023 / Accepted: October 19, 2023 / Published: October 30, 2023



Chemical safety
Assessment and classification of the danger of endocrine disruptors
Abstract
Научно-практический журнал «Токсикологический вестник» продолжает публикацию научно обоснованного списка эндокринных разрушителей, который лег в основу мето-дических рекомендаций МР 1.2.0313–22 «Оценка и классификация опасности эндо-кринных разрушителей», утвержденных Руководителем Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека А.Ю. Поповой 30 декабря
2022 г.


