Current issues in pharmacy and medicine: science and practice

Synthesis methods of 1,2,4-triazole-3-thiones: review

Yu. S. Frolova , A. H. Kaplaushenko, T. V. Ihnatova, T. M. Kaplaushenko — Fri, 14 Jun 2024 00:00:00 +0300

1,2,4-Triazole-containing compounds are unique heterocyclic compounds present in an array of pharmaceuticals and biologically important compounds used in drug-discovery studies against cancer cells, microbes, and various types of diseases in the human body.

The aim of the study was to analyze in detail and combine the available literature materials to study the reactions associated with the formation of different classes of derivatives of 1,2,4-triazole-3-thione and to study their physical-chemical properties.

Various innovative methods have been proposed and explored for synthesizing different classes of 1,2,4-triazole compounds, each with distinct applications and potential medicinal benefits. When analyzing the outcomes of studies aimed at obtaining new 1,2,4-triazole-3-thiones, it’s crucial to recognize the multiple stages involved in their synthesis. These stages typically include the esterification of carboxylic acids, hydrazinolysis, the formation of carbothioamides, and thiones through alkaline cyclization. Subsequently, reactions involving the S-function are conducted, leading to the formation of various classes of derivatives of 1,2,4-triazole.

The study by a team of scientists introduced a novel method for synthesizing imidazolyl- and imidazole-1,2,4-triazoles, targeting the design of safer analgesic and anti-inflammatory agents.

Moreover, researchers have successfully synthesized derivatives of 3-[2-(5-thio-4-aryl-4H-1,2,4-triazole-3-yl)ethyl]quinoxalin-2(1H)-one, N-(3-thio-5-aryl-[1,2,4]triazole-4-yl)acylamides, 5-alkylthio-4-amino-3-(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thiomethyl)-1,2,4-triazole and 3-(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thiomethyl)-6-aryl-5,6-dihydrogen-1,2,4-triazole-[3,4-b]-1,3,4-thiadiazole, 5,5’-(alkyldiyl-bis(sulfandiyl))bis(N-(arylidene)-3-thiophen-2-ylmethyl)-4H-1,2,4-triazole-4-amines, 3-(arylsulfonyl)-4-phenyl-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole, expanding the scope of 1,2,4-triazole-based, compounds with potential pharmacological activities. Furthermore, the synthesis of molecules containing two 1,2,4-triazole and two benzole rings has gained traction, offering new avenues for drug development.

Mannich bases were synthesized from the corresponding thiones through a reaction with N-methylpiperazine or N-phenylpiperazine in dimethylformamide in the presence of formaldehyde.

Additionally, the synthesis of salts derived from 1,2,4-triazole highlights its importance in pharmaceutical formulations, with studies focusing on both organic and inorganic salts for potential therapeutic applications.

Conclusions. The analysis of the above-mentioned publications indicates that the search for new biologically active compounds among derivatives of 1,2,4-triazole-3-thiones is promising. Many 1,2,4-triazole-3-thiones exhibit a wide spectrum of biological activity with little toxicity.

Anticancer properties of 1,2,4-triazole derivatives (literature review)

I. V. Bushuieva, M. V. Parchenko — Fri, 14 Jun 2024 00:00:00 +0300

Cancer is still one of the leading causes of death worldwide. Statistical data show that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organ and eventually the whole body. In most cases, cancer is a tumor affecting epithelial, mucous, muscle, fat, and bone tissues. Also, processes related to malignant formations can occur in the blood and lymph. The main mechanism that triggers the process of formation of neoplasms is a violation of growth and, accordingly, cell division. They begin to grow uncontrollably, multiply, and can also migrate, spreading to nearby tissue structures, and later degenerate into atypical (malignant) ones. Cancer is one of the most life-threatening diseases. Literature data show that more than 90 % of cancer patients die due to chronic metastases. Cancer therapy involves the use of drugs that block the growth and spread of cancer cells by affecting certain molecular structures involved in the growth, progression, and spread of cancer. The diversity of the use of means for cancer therapy, namely, hormone therapy, the use of angiogenesis inhibitors and apoptosis inducers, has provided scientists with various options for finding effective means to fight this disease.

Aim. The aim of the work is the analysis and systematization of new data on the anticancer activity of 1,2,4-triazole derivatives and the selection of the most promising directions for further scientific research based on the results of the analysis.

Materials and methods. The study employed various methods, including analysis, information search, bibliosemantic analysis, descriptive techniques, and generalization. Research materials primarily comprised literary sources containing information on the promising array of new biologically active compounds, particularly 1,2,4-triazole derivatives, known for their targeted anticancer properties.

Results. A literature search was carried out, 1,2,4-triazole derivatives with antitumor activity were analysed, characterized and summarized. Based on the study of available information and conducting an information and patent search, it was established that the market of Ukraine is insufficiently saturated with 1,2,4-triazole-containing drugs with anticancer activity of domestic production. It was determined that the development of new effective drugs based on 1,2,4-triazole and potential drugs with clearly directed anticancer activity requires a systematic approach both in conducting synthetic tests and screening new compounds for further structural optimization of molecules.

Conclusions. The analysis of scientific literature in recent years devoted to the study of the anticancer activity of 1,2,4-triazole derivatives convincingly proves the prospect of further research in this direction. Numerous publications indicate the possibility of constant improvement of molecules with regard to the presence of anticancer activity. Domestic and foreign authors have clearly and argumentatively proven the perspective of the scientific direction for the creation of new original drugs to combat various oncopathologies.

Some transformations in a series of 4-amino-1,2,4-triazole-3-thion derivatives

O. A. Bihdan, V. V. Parchenko, B. V. Gutyj — Fri, 14 Jun 2024 00:00:00 +0300

The continuous improvement of synthesis methods enables the optimization of the process for developing and obtaining target products of chemical transformation. Derivatives of 1,2,4-triazole-3-thiol present a convenient object for chemical transformation, facilitating the creation of promising biologically active compounds. Combining the structure of this heterocyclic system with pharmacophore fragments of different natures allows for more effective work on the development of molecules with high pharmacological potential. To implement this strategy, 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones were utilized as starting structures. This molecule possesses three reaction centers, facilitating a wide range of chemical transformations involving these substances.

The aim of the work was to create a series of 4-amino-2-((R₁,R₂-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones as a promising source for the preparation of biologically active substances.

Materials and methods. The structure of the target compounds has been formed using well-known methods of organic chemistry. The starting materials used were 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones, which were previously obtained. The first stage of the work involved the temporary protection of the amino group with a tert-butoxycarbonyl group. The second stage of the work involved the realization of Mannich reactions involving primary and secondary amines. The reaction has been carried out with formalin in an alcohol-dioxane medium. The products of the chemical transformation have been recrystallized in methanol. The third stage of the work was based on the removal of Boc-protection, which was realized using hydrochloric acid in a dioxane medium. The structures of all synthesized substances have been determined by ¹H NMR spectroscopy and elemental analysis. The individuality of the compounds has been confirmed by high-performance liquid chromatography.

Results. The successful study of the mechanisms of Mannich reactions for 4-amino-1,2,4-triazole-3-thione derivatives allowed us to obtain 4-amino-2-((R₁,R₂-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones in quantitative yields. The studies made it possible to establish the favorable effect of protecting the amino group of the 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione of the tert-butyloxycarbonyl group on the course and direction of the reaction.

Conclusions. The optimal conditions for the Mannich reactions involving 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione with intermediate Boc-protection of the amino group have been determined, which allowed us to create the theoretical basis for the successful use of Mannich reactions to expand the range of promising 4-amino-1,2,4-triazole-3-thione derivatives.

Comparison of phytochemical composition, antimicrobial, antifungal, and antioxidant activities of lipophilic and ethanolic green tea leaf extracts

Fri, 14 Jun 2024 00:00:00 +0300

Infection diseases are a worldwide important problem for medicine and pharmacy. Today, there is a high interest in the evolution of new antimicrobial drugs due to the increasing percentage of resistant bacteria and fungi strains. Green tea leaf contains a variety of natural compounds that are possible to apply in the creation of new antimicrobial drugs.

The aim of the work was to compare phytochemical composition, antimicrobial, antifungal activities of lipophilic and ethanolic green tea leaf extracts.

Materials and methods. The object of the research was the lipophilic extract obtained using chloroform, along with two ethanolic extracts of green tea leaves. One of the ethanolic extracts had been previously processed with chloroform, while the other had not. Antioxidant activity was determined by the potentiometric method, while antimicrobial and antifungal activities were assessed by the “wells” method.

Results. The lipophilic extract of green tea leaves contains predominantly caffeine and organic acids, with the lowest amount of phenolic compounds. In contrast, the ethanolic extracts show the opposite pattern, with phenolic compounds predominating and caffeine present in lower quantities. The lipophilic extract exhibits greater inhibition of the growth of S. aureus, E. coli, P. vulgaris, B. subtilis, and C. albicans compared to the 96 % ethanolic extract processed with chloroform, with inhibition rates of 19 %, 18 %, 12 %, 12 %, 16 %, and 20 % respectively. When comparing antimicrobial activity to the 96 % ethanolic extract without chloroform treatment, the results remained consistent. The antioxidant activity of the lipophilic extract was 58.7 and 60.0 times lower than that of the 96 % ethanolic extract processed with chloroform and the 96 % ethanolic extract without treatment, respectively.

Conclusions. The study revealed that the lipophilic extract exhibited greater inhibition of the growth of both Gram-positive and Gram-negative bacteria as well as fungi compared to the ethanolic extracts. However, it showed a lower level of antioxidant activity. It is hypothesized that caffeine, organic acids, and catechins may interact synergistically to enhance the antimicrobial and antifungal activity of green tea leaf extracts. The lipophilic extract shows promise for further development in the production of antimicrobial and antifungal drugs.

Pharmacological potential of 3,5-dimethyl-4-(3-(5-nitrofuran-2-yl)allylidenamino)-1-alkyl-1,2,4-triazolium bromides

A. S. Hotsulia, O. I. Panasenko, T. S. Brytanova — Fri, 14 Jun 2024 00:00:00 +0300

The discovery of new 1,2,4-triazole derivatives offers significant potential for the development of innovative medications. Researchers often favor derivatives of this heterocyclic system due to their ability to create chemical structures with desired pharmacokinetic and pharmacodynamic properties, allowing for targeted effects on specific biological targets. Importantly, biologically active compounds containing triazole have demonstrated relatively low toxicity and minimal risks of mutagenicity. The synergistic combination of these characteristics provides favorable conditions for the development of complex therapeutic effects, ultimately leading to the creation of novel biologically active substances and offering new avenues for the effective treatment of various diseases.

Indeed, the utilization of a diverse array of chemical transformations and functionalizations is crucial for obtaining bioactive molecules with desired properties. In this context, 1,2,4-triazole and its derivatives offer a platform for executing a comprehensive range of chemical transformations, thereby enabling the development of compounds with enhanced pharmacokinetic and pharmacodynamic parameters.

The aim of the study was to preliminarily assess the possibility of creating a biologically active substance based on 3,5-dimethyl-4-(3-(5-nitrofuran-2-yl)allylidenamino)-1-R-1,2,4-triazole halides.

Materials and methods. In silico analysis was used to assess the safety and potential toxicity of the presented compounds, which was implemented using the T.E.S.T. software developed by the US Environmental Protection Agency. SwissADME is an online resource as an effective tool for studying the physicochemical properties and pharmacokinetic parameters of the compounds proposed for study. A molecular docking method that uses a variety of computational algorithms to predict and analyze interactions, including determining the presence of possible binding sites, estimating binding energies, and the spatial arrangement of molecules. The ligand models were created using MarvinSketch 6.3.0, Hyper Chem 8, and AutoDockTools-1.5.6. Discovery Studio 4.0 and AutoDockTools-1.5.6 have been used to prepare the enzymes for analysis. For direct molecular docking, Vina software has been used, which allows predicting and evaluating the interaction between the ligand molecule and the three-dimensional structure of the target protein, taking into account their energy and spatial compatibility.

Results. A virtual set of 3,5-dimethyl-4-(3-(5-nitrofuran-2-yl)allylidenamino)-1-alkyl-1,2,4-triazolium bromides was prescreened, which are potential candidates for the further synthesis of biologically active compounds. The general level of toxicity and harmlessness was determined at the predictive level. The key physicochemical characteristics of the molecules have been determined and the general pharmacokinetic parameters have been identified, which allows for a better understanding of their interaction and behavior in the body. The active sites of the model enzymes were analyzed using Vina software, which contributes to a deeper understanding of the interaction of enzymes with their substrates.

According to the results of the study, an increased probability of the formation of anti-inflammatory and anticancer properties occurs in 1-alkyl derivatives of 3,5-dimethyl-4-(3-((5-nitrofuran-2-yl)allylidenamino)-1,2,4-triazolium halides with an odd number of Сarbon atoms. Instead, the highest affinity for lanosterol 14α-demethylase has been demonstrated in the studied derivatives with octyl and nonyl substituents, which shows a certain probability of antifungal activity.

Conclusions. The prognosis for the creation of a biologically active substance using 1-alkyl derivatives of 3,5-dimethyl-4-(3-(5-nitrofuran-2-yl)allylidenamino)-1,2,4-triazolium halides is quite favorable.

The anatomical and micromorphological structure of Myrtus communis L. leaves

O. Ye. Matsehorova, V. M. Odyntsova — Fri, 14 Jun 2024 00:00:00 +0300

Myrtus communis L. is a promising medicinal plant that has garnered the attention of scientists to introduce it into industrial cultivation as a raw material source for obtaining new phytopreparations. In its chemical composition, Myrtus communis L. contains many biologically active substances, which confer upon it a range of medicinal properties including astringent, anti-inflammatory, antiviral, antibacterial, antifungal, antioxidant, antidiabetic, antiulcer, antimutagenic, gastro- and hepatoprotective properties. Published information primarily focuses on the chemical composition and pharmacological activity of common myrtle, with limited data available on its micromorphology.

The aim of the work is to study the morphological and anatomical structure and to determine the general diagnostic microscopic features of common myrtle leaves.

Materials and methods. The object of the research was fresh and dried plant material of common myrtle grown under room conditions. Transverse sections were fixed with Carnois fixative, dehydrated, and paraffinized. The sections were then cut using a Microm HM 325 microtome, followed by deparaffinization. Microscopic analysis of the leaf was performed using temporary preparations on a Carl Zeiss microscope, including the “AxioStar Plus” and “Primo Star”, equipped with a photo attachment for direct and reflected light microscopy.

Results. The external features of common myrtle leaves include their shape, color, size, smell, and type of veining. Anatomically, the leaves exhibit a cuticle, dorsiventral mesophyll, and anomocytic stomata located on the abaxial surface. Additionally, they contain calcium oxalate crystals and druses, as well as simple hairs on the midvein and schizolisogenic secretory receptacles. Histochemical studies of these cavities indicate the presence of lipophilic substances.

Conclusions. The morphological and anatomical analysis of Myrtus communis L., a representative of the myrtle genus, allowed for the identification of key diagnostic microscopic features of myrtle leaves. Further research prospects involve conducting a comprehensive set of phytochemical studies to establish standardization parameters for medicinal plant raw materials.

Study of the ascorbic acid accumulation in Thymus L. genus species of Ukraine flora

O. V. Mazulin, Ya. M. Steshenko, L. A. Fukleva, H. V. Mazulin — Fri, 14 Jun 2024 00:00:00 +0300

The Thymus L. genus species are extremely widespread in temperate countries and number up to 200 main wild plants, of which up to 50 have been identified in the modern Ukraine flora. Extracts from the official species of the Thymus L. genus are part of effective herbal preparations with pronounced anti-inflammatory, antimicrobial, and antioxidant activities. A promising direction of modern phytochemical research is the determination of the presence and accumulation of biologically active ascorbic acid in the herbs of widespread wild and cultivated species of the Thymus L. genus.

The aim of the work is to determine the presence and accumulation of biologically active L-ascorbic acid in the herbs of four widespread wild and cultivated species of the Thymus L. genus of Ukraine flora using thin layer chromatography (TLC) and spectrophotometry methods during vegetation season.

Materials and methods. The research used herbs of four widespread wild and cultivated species of the Thymus L. genus of Ukraine flora during the growing season (June – August 2023). The presence and quantitative content of ascorbic acid were determined by TLC on a “Biostep” CD 60 densitometer (Germany) and spectrophotometry on a “Lambda 365’ device (USA).

Results. TLC and spectrophotometry methods were used to determine the presence and quantitative content of ascorbic acid in the herbs of four widespread Thymus L. genus species of Ukraine flora during the growing season. Accumulation of the compound was higher during flowering of cultivated species than wild plants. For the herbs Thymus vulgaris L. up to 39.10 ± 3.88 mg%; Th. x citriodorus (Pers.) Schreb. var. “Silver Queen” up to 36.19 ± 3.59 mg%.

Conclusions. Considering the results obtained by TLC and spectrophotometry methods, it can be concluded that the determination of ascorbic acid presence and content in the Thymus L. species genus herbs is appropriate for obtaining cosmetology preparations with pronounced anti-inflammatory, antioxidant, and regenerating activity for normal and problem skin.

Comparative studies of essential oils from Matricaria recutita L.

O. I. Panasenko, V. M. Odyntsova, O. M. Denysenko, V. I. Mozul, V. V. Holovkin — Fri, 14 Jun 2024 00:00:00 +0300

The aim of the work is to determine the component composition of the essential oil of medicinal chamomile, grown on the educational and research site of medicinal plants of Zaporizhzhia State Medical and Pharmaceutical University (ZSMPHU), and commercial essential oil that was purchased via the Internet.

Materials and methods. The object of the study was chamomile essential oil obtained by hydrodistillation and commercial oil. Qualitative and quantitative determination of the components of essential oils was established using the chromato-mass spectrometric method on a high-performance gas chromatograph “Agilent 7890B GC System” (Agilent, SantaClara, CA, USA) with a mass spectrometric detector “Agilent 5977 BGC/MSD” (Agilent, SantaClara, CA, USA).

Results. Dominant compounds of essential oil of chamomile, grown on the educational and research site of medicinal plants ZSMPHU were 2H-pyran-3-ol, tetrahydro-2,2,6-trimethyl-6-(4-methyl-3-cyclohexen-1-yl) ) – 7.54 %, chamazulene – 5.32 %, alpha-bisabolol – 4.30 %, 1H-cycloprop[e]azulen-7-ol, decahydro-3,1,7-trimethyl-4-methylene – 3.25 %, myrtenyl acetate – 3.03 %, azulene, 1,2,3,3a,4,5,6,7-octahydro-1,4-dimethyl-7-(1-methylethenyl) – 2.16 %, bisabolol oxide B – 1.86 %. Commercial chamomile essential oil was dominated by 3-methoxy-3-methylbutanol (56.15 %), diethyl phthalate (17.46 %), linalyl acetate (6.99 %), linalool (4.41 %).

Conclusions. Industrial cultivation of chamomile in southern Ukraine shows a high biologically active substances content and can be in demand in the pharmaceutical industry’s consumer market for raw materials.

Development of the optimal composition of tablets with the active substance potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate. Message 1. Study of the effect of auxiliary substances on bulk density, bulk density after shrinkage, fluidity and angle of natural slope of powder masses

R. O. Shcherbyna, O. V. Khromylova, H. R. Nimenko, V. O. Salionov — Fri, 14 Jun 2024 00:00:00 +0300

The pharmaceutical industry continually evolves to meet the demands of modern society for high-quality medications. One avenue of this advancement involves exploring new technologies for manufacturing tablet formulations that adhere to contemporary quality standards. An integral aspect of this process is the careful selection of optimal excipients that preserve the pharmacological activity of the active substance to the greatest extent possible. Investigating the impact of various excipients on the tablet compression process is pivotal to addressing this challenge. Therefore, the study of the influence of excipients on the pharmaco-technological properties of tablets with potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate is an important aspect, so as this substance has pronounced hepatoprotective and antioxidant properties.

The aim of the work was to study the effect of excipients on the pharmaco-technological parameters of tablets with the active ingredient potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate obtained by the method direct pressing.

Materials and methods. Active substance – potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate, auxiliary substances (excipients based on microcrystalline cellulose, auxiliary substances based on granulated sugars, lubricants, lubricants). The powder mixtures were checked for bulk density, bulk density after compaction, flowability and angle of natural slope. The tablets were pressed by the direct pressing method. The effect of auxiliary substances on the pressing process was studied.

Results. The conducted studies show that the powder mass of potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate and auxiliary substances was characterized by good pharmaco-technological indicators – bulk density and bulk density after compaction, fluidity and angle of natural slope. Further, during the tableting process, it was confirmed that the powder mass has satisfactory properties. In almost all series of experiments, the process of pressing the tablets took place without difficulties, the matrix was evenly filled, but the force of pushing the tablets out of the matrix was different.

Conclusions. The study involving 16 excipients, including fillers, disintegrants, and lubricants to develop the composition and technology was conducted of a new tablet medicine containing potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazole-3-yl)thio)acetate. This comprehensive examination enabled us to identify the optimal auxiliary substances that fulfill all the pharmaco-technological requirements stipulated by the State Pharmacopoeia of Ukraine for tablet formulations.

Study of the effect of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)- 4H-1,2,4-triazole-3-yl)thio)acetate toxic doses on rats heart tissue

A. A. Safonov, O. I. Panasenko, N. A. Al Khalaf — Fri, 14 Jun 2024 00:00:00 +0300

Analysis of medicinal product safety is an important stage on the way to the entry of a synthetic compound into the pharmaceutical market. Along with the study of blood composition, scientists are actively analyzing the effect of toxic doses on the tissues of internal organs. Analyzing the toxic effect of compounds on heart tissue allows us to find out what damage substances can cause, which can have a direct impact on human health. Today, 1,2,4-triazole derivatives are very relevant and a huge number of publications is a confirmation of this.

The aim of the work was to analyze the effect of toxic doses of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate on rats heart tissue.

Materials and methods. Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate (ASP) was selected as the subject of investigation and administered intragastrically in the form of a suspension with purified water using a specialized metal probe. The toxic effect on tissues was analyzed using doses of 1000 mg/kg, which is 10 times higher than a single dose typically used in pharmacological activity studies, and 5000 mg/kg, which represents the limit for determining acute toxicity and the maximum dose within the fourth class of toxicity, considering the route of administration, provided that this dose does not result in the death of the animal.

Analysis of the effect of toxic doses of ASP was performed on 12-month-old purebred male rats kept under standard conditions. Rat heart tissues were fixed for further histological examination in a 10 % formaldehyde solution, dehydrated in alcohols of increasing strength, and embedded in paraffin.

Results. Macroscopic and microscopic analysis of rat heart tissue was carried out. The research shows the histological results of deviations from the norm for a group of rats that were injected with substances in the studied doses.

Conclusions. The effect of toxic doses of ASP on rat heart tissue was analyzed. For a dose of 1000 mg/kg, local signs of protein dystrophy of cardiomyocytes and single loci of hemorrhages are observed. As for the dose of 5000 mg/kg, the effect of the substance on the heart tissue is more profound and is determined by the selective damage of cardiomyocytes with the loss of lumbar striation and the acquisition of a wave-like shape, full blood is observed in the ectasized capillaries.

Fruit extracts of various cornelian cherry (Cornus mas L.) cultivars as antioxidant therapy for alleviating nitrative stress in erythrocytes of blood in experimental diabetes mellitus

I. V. Brodyak, A. A. Moroz, A. Z. Kucharska, N. O. Sybirna — Fri, 14 Jun 2024 00:00:00 +0300

Natural antioxidants (vitamins, bioflavonoids, anthocyanins, etc.) are used to prevent the development of oxidative-nitrative stress in diabetes mellitus (DM), which helps to restore or avert functional disorders in the cells and tissues of the body.

The aim of the study is to investigate the effect of extracts of the fruit of different cultivars of the cornelian cherry, as well as their main iridoid glycoside – loganic acid, on the activity of NO-synthase and the content of stable metabolites of NO in blood erythrocytes of rats with streptozotocin-induced diabetes.

Materials and methods. In the work, we used the extract of the fruits of the cornelian cherry “Podolski” cultivar (BDPA 10462), the ripe fruits of which have a red color, and the extract of the “Yantarnyi” (BDPA 14131) and “Flava” (BDPA 8795) cultivars, the ripe fruits of which have a yellow color. Loganic acid was extracted from yellow fruits of the “Yantarnyi” and “Flava” cultivars of Cornus mas L. All studied extracts were administered to rats orally for 14 days from the 10th day after the induction of DM. The dose of administration was 20 mg/kg body weight.

Results. The extract of the red fruits is demonstrated the most pronounced effect in normalizing the biomarkers of nitrative stress (activity of NO-synthase and its isoforms, the content of nitrite and nitrate anions) in erythrocytes of rats with diabetes. The extract of the yellow fruits shows a positive effect on the suppression of nitrative stress, which has been indicated by a decrease in the activity of iNO-synthase to the values in the control group of animals. Loganic acid, on the contrary, inhibited the eNO-synthase. In addition, the extract of yellow fruits of cornelian cherry and loganic acid decreased the level of NO₃^– and increased the content of NO₂^– in erythrocytes of diabetic rats.

Conclusions. Biomarkers of nitrative stress in erythrocytes of rats with streptozotocin-induced diabetes indicated the antioxidant properties of fruit extracts of cornelian cherry, in particular the red fruits, which contain a large amount of anthocyanins.

Diagnostic significance of immunological parameters in predicting the development of pneumonia in adult patients with measles

Fri, 14 Jun 2024 00:00:00 +0300

The aim of the study is to determine the diagnostic significance of immunological parameters in predicting the development of pneumonia in adult patients with measles.

Material and methods. The study examined 88 patients aged 21 to 55 years diagnosed with measles according to the World Health Organization’s criteria (2013). Enzyme-linked immunosorbent assay (ELISA) was used to determine IgG levels to the measles virus (Vircell Microbiologists, Spain) and the levels of interferon-γ (IFN-γ) (Invitrogen, Austria). Statistical analysis was conducted using Statistica 13 for Windows (StatSoft Inc., No. JPZ804I382130ARCN10-J).

Results. According to the results of the study, it was found that upon hospitalization on the 4.8 ± 0.2 day of the disease, 71.6 % of patients were seropositive for IgG to measles virus. The development of measles pneumonia was associated with the lowest level of IgG to measles virus (p < 0.01). When the level of IgG to measles virus at hospitalization of adult patients was ≤20.26 optical units, the probability of developing measles pneumonia was significant (AUC = 0.650, p = 0.016).

In adult patients with measles, the serum IFN-γ level at the height of the disease was higher (p < 0.05) than in healthy individuals. Upon hospitalization on the 4.8 ± 0.2 day of the disease, the level of IFN-γ in the setting of pneumonia was the highest (p < 0.05), exceeding the corresponding parameter in patients without complications. The level of IFN-γ at hospitalization >1.90 pg/ml was diagnostic for predicting the likelihood of pneumonia (AUC = 0.643, p = 0.038).

The authors present their clinical observation, which demonstrates the informative value of using the established immunological parameters in clinical practice to predict the likelihood of pneumonia in adult patients with measles.

Conclusions. The diagnostic significance of such immunological parameters as IgG to measles virus and IFN-γ in predicting the development of pneumonia in adult patients with measles at the time of hospitalization has been proved. Our clinical observation demonstrates the informativeness of the established prognostic markers.

Epidemiology of pancreatic cancer in Ukraine and Zaporizhzhia region

M. A. Shyshkin, V. O. Kabachenko — Fri, 14 Jun 2024 00:00:00 +0300

The aim of the work is to analyze the incidence and mortality of pancreatic cancer (PC) in Ukraine and the Zaporizhzhia region to highlight and compare the organization of oncological care, the benefits of prevention, and early diagnosis of this disease.

Materials and methods. The analysis of the data of the National Cancer Registry of Ukraine for 2014–2022 was carried out. The information used in the research was reviewed and approved by the Commission on Bioethics of Zaporizhzhia State Medical and Pharmaceutical University, an extract from protocol No. 10 dated 12/21/2023. The data analysis was carried out using Microsoft Excel spreadsheets and the applied statistical program Statistica® for Windows 13.0 (StatSoft Inc., USA, license No. JPZ804I382130ARCN10-J).

Results. According to GLOBOCAN data (2022), RP ranks 14th in the world and 12th in Ukraine in morbidity and is one of the leading causes of mortality. Every year there is an increase in cases of this pathology. Morbidity and mortality rates are significantly higher in countries with a high level of development, while the survival rate does not reveal such a dependence. Mortality from PC in Ukraine is 76.9–82.3 %, in the Zaporizhzhia region 86.2–99.5 % with positive dynamics. Detection of early stages of PC in Ukraine and the Zaporizhzhia region is at the level of 26.0–36.4 %, 30.7–43.6 %, respectively, diagnosis of advanced stages is at the level of 43.8–56.3 % across Ukraine, in the Zaporizhzhia region – 58.6–63.2 %. In Ukraine, 25.3–31.9 % of primary patients are covered by special treatment, the regional indicator is 17.9–26.6 % with positive dynamics. The effectiveness of primary prevention of PC in Ukraine reaches 3.3 %, the regional indicator does not exceed 3.0 %.

Conclusions. Improvement of preventive measures, selection of groups at risk of development of PC, modification of lifestyle are factors for improvement of prognosis and survival of patients with PC.

Steroid-induced dermatoses: a challenge for modern dermatology

H. I. Makurina, L. O. Cherneda — Fri, 14 Jun 2024 00:00:00 +0300

The aim of this work is to determine the variability and significance of motivating and provoking factors associated with the uncontrolled use of topical glucocorticosteroids, psychological features of this condition.

Materials and methods. 50 patients with exacerbation of inflammatory dermatoses after long-term topical application of drugs with glucocorticosteroids as an active substance were examined. The key diagnostic measures were a clinical examination, an anamnesis collection with clarification of the activity class of the used agent, duration and potential reason for its systematic or periodic use. Assessment of the psycho-emotional state in relation to self-perception of one’s own body was carried out using the dermatological version of the dysmorphic disorder questionnaire – BDDQ-DV.

Results. The main pathology for which patients of both sexes used this group of drugs were rosacea, perioral dermatitis, and seborrheic dermatitis. Taking into account anamnestic data, the mean duration of application of topical corticosteroids in creams, ointments or lotions was 10.25 ± 3.50 months for women and 8.3 ± 1.6 months for the male cohort. Most patients received information about the need to use a topical steroid from acquaintances / friends and pharmacists. The most frequent pharmacological agent was betamethasone dipropionate.

Analyzing the psychopathological aspect of the studied group, dysmorphic manifestations are prevalent and the most well argued. 32 individuals (64 %) from the cohort met the criteria for concern about the body or its parts.

Conclusions. Regional clinical features of steroid-induced dermatoses, which are mostly represented by chronic inflammatory conditions located in aesthetically significant areas, have been determined. 64 % of patients with steroid-induced dermatoses develop a psychopathological profile. An important aspect remains the necessity to raise the awareness of medical, pharmaceutical workers, and the public about the need and correct use of topical corticosteroids.

Analysis of the efficiency of theoretical knowledge and practical skills acquisition by intern doctors using the “Body Interact” virtual patient simulator in the conditions of today’s challenges

M. Yu. Kolesnyk, Ya. M. Mykhailovskyi — Fri, 14 Jun 2024 00:00:00 +0300

The aim of the work is to evaluate the efficiency of theoretical knowledge and practical skills acquisition by intern doctors using the body interact virtual patient simulator in distance (offline) and traditional (online) form of education.

Materials and methods. The study involved 22 interns in the second year of study of the specialty “Internal Diseases”. 17 of them studied in offline format, 5 – in distance (online) format. The efficiency of theoretical knowledge acquisition was evaluated based on the results of the Integrated License exam “KROK 3. General Medical Training”. The efficiency of practical skills acquisition was determined by passing scenarios of providing medical care using the virtual patient simulator “Body Interact”.

Results. It has been established that the effectiveness of traditional (offline) and distance (online) learning is comparable in terms of theoretical knowledge acquisition which is evidenced by the comparative results of passing the Integrated License exam “KROK 3. General Medical Training”. The results of passing the state license integrated exam “KROK 3. General medical training” and the virtual patient “Body Interact” had no correlation, which indicates the insufficient representativeness of the test assessment regarding the practical skills acquisition. Traditional (offline) learning is more effective in practical skills acquisition, which is confirmed by the better results of passing scenarios of providing medical care using the virtual patient program “Body Interact” in the group of traditional form of education compared to the group of online learning.

Conclusions. Utilizing virtual patient simulation technology such as “Body Interact” in the training of intern doctors not only enhances the acquisition of theoretical educational material but also offers an opportunity to practice practical skills. This is particularly valuable in light of resource constraints resulting from COVID-19 and martial law. Implementing the “Body Interact” virtual patient technology into daily educational practices, especially in the context of distance learning, is advisable.