Annals of Mechnikov's Institute https://journals.uran.ua/ami AMI is an open-access and peer-reviewed journal with a transdisciplinary focus on medicine (microbiology and immunology) and pharmacy. It is fee-free journal for authors with free open access to PDF full-format articles. State institution "I. Mechnikov Institute of Microbiology and Immunology of NAMSU" en-US Annals of Mechnikov's Institute 2519-4224 Multidisciplinary context of research of a new drug in infectious and inflammatory diseases https://journals.uran.ua/ami/article/view/306931 <p><strong>Introduction.</strong> The multidisciplinary context of the study of a new drug for infectious-inflammatory diseases based on the combination of evidence-selected pharmacological substances paracetamol and ascorbic acid was developed. Competences of the organization of pharmacy, medicine, pharmacology, forensic pharmacy, pharmaceutical analysis, and social medicine were used. <strong>The aim:</strong> Noted that the raw material base, production in the conditions of pharmacies and pharmaceutical enterprises of paracetamol + ascorbic acid tablets is economically expedient, socially oriented in the conditions of a military conflict. <strong>Materials and methods.</strong> Quality control methods have been developed: determination of para-aminophenol, paracetamol, and ascorbic acid. The results of organizational, documentary, pharmacological, medical, pharmaceutical, physicochemical, and social studies were used. According to physical and chemical studies, the determination of para-aminophenol by spectrophotometric method is proposed. It was determined that experimental samples of the drug do not contain impurities of free para-aminophenol. The maximum permissible content of para-aminophenol in tablets of the drug under study is no more than 0.1%. <strong>Results. </strong>The complex of developed methods and standardization of quality control indicators of paracetamol + ascorbic acid tablets meet the requirements of the latest pharmacopoeias. The methods of quantitative determination of the active substances of the drug used in the development of analytical and control documentation, the system of quality control of the drug in further production in the conditions of pharmacies or pharmaceutical enterprises. <strong>Conclusions.</strong> The main areas of application of paracetamol + ascorbic acid tablets are indicated: infectious diseases with an increase in temperature; pain syndromes of weak and medium intensity of various genesis. Appeared promising to include the new drug in the pharmacotherapy schemes of health care institutions. The social context of the study is relevant in emergency situations, in the conditions of a military conflict, to reduce the suffering of victims of pain, inflammation, fever, and improve the quality of life of patient</p> <p>Keywords: <span class="pkpBadge">paracetamol </span><span class="pkpBadge"> ascorbic acid </span><span class="pkpBadge"> analysis </span><span class="pkpBadge"> application </span></p> Valentyn Shapovalov Viktoriia Shapovalova Alina Osyntseva Valerii Shapovalov Oleksandr Veits Yurii Titarenko Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 3 9 10.5281/zenodo.13820208 Antimicrobial action of α-arbutin, β-arbutin and hydroquinone: truth and fiction https://journals.uran.ua/ami/article/view/310333 <p><strong>Introduction</strong>. The leaves of lingonberry and bearberry are used in medicine for the treatment and prevention of urological infectious diseases due to the presence of diuretic and uroseptic action. This pharmacological activity is associated with the action of β-arbutin and hydroquinone. However, until now there has been no study of the relationship between the structure and antimicrobial action of β-arbutin and hydroquinone. The purpose of study was to estimate the antimicrobial action <em>in vitro</em>, <em>in silico</em> of α- and β-arbutin, hydroquinone, and also to conduct a comparative analysis of the antimicrobial properties of these compounds and to refute the theory of the presence of the antimicrobial action of arbutin only due to the action of hydroquinone.<strong>Materials and methods</strong>. Molecular docking was performed using AutoDockTools 1.5.6, antimicrobial activity was assessed using the "well" and "dilution" methods. <strong>Results and discussion.</strong> Theoretical studies have shown that α- and β-arbutin are highly selective inhibitors against gram-negative targets such as deoxyribonucleic acid (DNA) gyrase, dihydrofolate reductase (DHFR), deacetylase, and fungal targets such as 14α-demethylase, beta-1,3-glucanase, thymidylate kinase, whereas hydroquinone had low selectivity against all targets. The "well" assay showed that hydroquinone inhibits gram-positive bacteria more actively than β- and α-arbutin, and in the case of gram-negative bacteria, α-arbutin had a higher inhibitory effect than β-arbutin and hydroquinone, while β-arbutin inhibits fungal growth more actively than α-arbutin and hydroquinone. The minimum inhibitory concentration (MIC) values ​​of hydroquinone for gram-positive, gram-negative and fungal microorganisms were almost 2-3 times higher than MIC of β- and α-arbutin. Meanwhile, MIC of α-arbutin was lower for <em>E. coli, P. vulgaris</em> than β-arbutin, and the results were the same in other cases. Conclusions. The antimicrobial effect of α- and β-arbutin, hydroquinone against strains of <em>S. aureus</em>, <em>B. subtilis</em>, <em>E. coli, P. vulgaris, P. aeruginosa</em> and <em>C. albicans</em> was studied <em>in vitro</em> and <em>in silico</em>. Theoretical results showed that it is impossible to create a "panacea" from one compound that would suppress the growth of both bacteria and fungi. According to theoretical and practical results, the antimicrobial effect of α- and β-arbutin is 2-3 times higher than that of hydroquinone. It has been experimentally confirmed that α-arbutin suppresses the growth of gram-negative strains much more strongly than β-arbutin. The theory that arbutin has an antimicrobial effect only due to the action of hydroquinone has been theoretically and practically refuted.</p> <p><strong>Keywords: </strong>hydroquinone, hydroquinone glycosides, structure-action relationship, comparative analysis, molecular docking</p> Oleksandr Maslov Mykola Komisarenko Svitlana Ponomarenko Tetyana Osolodchenko Artem Marchenko Dmytro Plis Andrey Komisarenko Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 10 19 10.5281/zenodo.13820076 Study of morphological and anatomical characteristics of Cosmos (Cosmos bipinnatus cav.) Herb https://journals.uran.ua/ami/article/view/311081 <p><em>Cosmos bipinnatus</em> Cav., or Mexican aster, from the aster family (<em>Asteraceae</em>) is an annual herbaceous plant that is common in the southwestern United States and Mexico. It is widely cultivated in many countries of the world, as well as in Ukraine as an ornamental plant. The plant is rich in carbohydrates, phenolic and nitrogen-containing compounds, terpene substances, and mineral elements. The chemical composition of the plant and the pharmacological effect of BAS complexes by scientists from different countries of the world have been studied. The anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, larvicidal, and insecticidal effects of raw materials and biologically active complexes of cosmeia bipinnate have been revealed. We also conducted phytochemical studies of the raw materials of this plant of domestic origin, which creates prospects for the development of medicinal products based on it. In order to include cosmeia bipinnate in the assortment of pharmacopoeial plants of Ukraine, it is necessary to develop criteria for standardization of raw materials according to the requirements of the Federal State Administration of Ukraine, among which there is conformity according to morphological (identification A) and anatomical (identification B) features. For standardization, we chose cosmeia bipinnate herb. <strong>The aim of the work</strong> was to study the morphological and anatomical diagnostic features of the cosmeia bipinnate herb. <strong>Materials and methods</strong>: <em>Cosmos bipinnatus </em>herb, a mixture of the most popular in Ukraine varieties Dazzler, Purity and Pink sensation <em>Cosmos bipinnatus</em> Cav., was chosen as the research object. The raw material was harvested in the flowering phase of the plant in July - August 2023 - 2024 in the Kharkiv region, Ukraine. For the experiments, fresh and air-dried raw materials were used, which were dried in the shade. The anatomical structure was studied using a Granum microscope at a magnification of 40-600 times, photographed with a ScienceLab DCM820 microscope camera, the photos were processed in TSView 7 and Adobe Photoshop CC 2021 programs. Fresh raw materials for anatomical research were fixed in a mixture of ethanol - glycerol - water (1:1:1), air-dried raw materials were clarified in chloral hydrate. Preparations of the epidermis of the stem, leaf, ligulate and tubular flowers, bracts of involucre, as well as cross-sections of the stem were prepared for microscopic study. Morphological characteristics of raw materials were determined visually with the naked eye and with a magnifying glass (x10).<strong>Research results:</strong> the following morphological diagnostic features of cosmeia bipinnate whole herb include: cylindrical stems, often hollow in the central part, pubescent. The leaves are pinnatisected and double pinnatissected into linear elongated segments, sessile, opposite, pubescent, pinnate venation. Inflorescences are capitula located on long axes. The marginal flowers are colored in white, pink or red-purple color, the middle ones are yellow. The smell of raw materials is characteristic. Anatomical diagnostic features of the examined herb include: cells of the upper and lower epidermis of the leaf are parenchymal, polygonal, with weakly sinuous walls, stomata of anomocytic type, and anisocytic type also on the lower epidermis. The epidermis is pubescent on both sides with multicellular caterpillar-like hairs with a broad base, 2-3 cell thick-walled conical and unicellular papilla-like hairs. There are simple 3-4 cell thick-walled hairs along the edge of the leaf. The veins of the leaf are accompanied by secretory ducts with brown contents. The cells of the upper and lower epidermis of marginal flowers are elongated along the veins, the cell walls are thin and wavy. Sometimes there are simple multicellular hairs. Papillary hairs are numerous. Veins are accompanied by secretory ducts with brown contents. The cells of the epidermis of tubular flowers are parenchymal at the edge, straight, thin-walled and tortuous in the central part. Stomata of the anomocytic type. Simple multicellular conical and glandular hairs with a multicellular head are present. Caterpillar hairs are rare. On the epidermis of marginal and tubular flowers, there are oval essential oil glands, which consist of two rows of cells arranged in four tiers, there are secretory ducts with brown contents and spherical pollen grains with a sharp-toothed surface. The epidermis of the leaves of the outer wrapper is convolute-walled with thickened membranes, the cells are elongated along the edge, the edge of the leaves is covered with numerous simple multicellular and club-like hairs, there are essential oil glands and secretory ducts with brown contents.</p> <p><em><strong>Key words:</strong> Cosmos bipinnatus </em>herb, <em>Cosmos bipinnatus </em>Cav<em>.</em>, morphological characteristics, anatomical characteristics, microscopic examination, raw material standardization.</p> Amina Deineka Iryna Zhuravel Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 20 30 10.5281/zenodo.13820033 Immunization schedule in Ukraine: history of implementation and list of vaccines https://journals.uran.ua/ami/article/view/306848 <p><strong>Introduction. </strong>Vaccination is a global health success story that saves millions of lives (WHO). Every year, thanks to it, it is possible to prevent 3.5-5 million deaths from such diseases as diphtheria, tetanus, whooping cough, influenza and measles. <strong>The purpose of our study</strong> was to conduct a comparative analysis of changes in the Immunization schedule of Ukraine for 1996-2022 and establish a list of registered vaccines in accordance with it. <strong>Material &amp; methods. </strong>The research materials were the orders of the Ministry of Health of Ukraine and data from the State Register of Medicines of Ukraine. The method of data systematization, generalization and comparative analysis was used. <strong>Results &amp; discussion. </strong>A study of the history of immunization schedule of Ukrainian for 1996-2022 showed that during this time the scheme of mandatory vaccination against measles did not change, but against tuberculosis, poliomyelitis, diphtheria, whooping cough, tetanus, epidemic parotitis and rubella – changed, mainly with regard to the timing of revaccination. Also, since 2011, vaccination against hepatitis B has been included in the immunization schedule . As of April 2024, 30 vaccines have been registered in Ukraine to ensure the vaccination calendar, the production of which involves 39 manufacturers from different countries, the largest of which are from Belgium and India (8 each, 20.5% each), France (6, 15.4%), Hungary (5, 12.8%) and Indonesia (4, 10.3%). The largest number of vaccines are produced by Sanofy (France, Hungary, Canada) (12 vaccines, 30.8%), GlaxoSmithKline Biologicals S.A., Belgium (8, 20.5%) and Serum Institute of India. Pvt. Ltd., India (7, 17.9%). Most vaccines (10, 33.3%) are intended for vaccination against one of the diseases (hepatitis B, tuberculosis, measles, poliomyelitis 1, 2, 3 types, poliomyelitis 1 and 3 types). <strong>Concliusions.</strong> Changes in immunization schedule of Ukraine for the period 1996 - 2022 mainly related to vaccination schemes against tuberculosis, poliomyelitis, diphtheria, whooping cough, tetanus, epidemic parotitis and rubella, and since 2011 vaccination against hepatitis B has been introduced as mandatory. The schedule provides for the prevention of 10 infectious diseases, while currently 30 relevant vaccines are registered in Ukraine.</p> <p><strong>Keywords</strong>: vaccination, immunization schedule, vaccines</p> Kateryna Dorykevych Yuliia Kremin Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 31 39 10.5281/zenodo.13819995 Monitoring of time stability of antimicrobial effect of nisin-based pharmaceutical compositions with resistance inhibitors https://journals.uran.ua/ami/article/view/311834 <p><strong>Introduction. </strong>The combination of nisin with resistance inhibitors, which do not have a direct antimicrobial effect but bind bacterial resistance factors in one way or another, restoring their sensitivity to classical antibiotics, is a promising area of medical science. However, combinations of these agents face the problem of drug stability, preservation of its therapeutic properties, especially antibacterial action. <strong>The aim of the work</strong> to study the stability of the antibacterial effect of pharmaceutical compositions based on nisin, diclofenac sodium and amlodipine for the treatment of infectious and purulent inflammatory diseases over time. <strong>Materials &amp; methods. </strong>The antimicrobial activity of 1.0 % aqueous solutions of unmodified and modified nisin with chelating agents was determined. Modified nisin was obtained by acylation of nisin with acetic anhydride. Diclofenac sodium and amlodipine were used as the chelating agents. For the microbiological study of the investigated substances, reference test cultures of gram-positive and gram-negative bacteria belonging to different taxonomic groups were used:&nbsp; The antimicrobial activity of the test substances was determined by the diffusion method of “wells” with the measurement of the diameters of the zones of inhibition of microbial growth. <strong>Results &amp; discussion. </strong>It was found that after storage for 1 month of the pharmaceutical composition of unmodified nisin with diclofenac sodium, its moderate antimicrobial effect against both test strains of gram-positive microorganisms was maintained. After storage for 2 months, the antimicrobial effect of the double composition of nisin with diclofenac sodium decreased within the range of moderate and decreased to weak after 3 months of observation. After 3 months of storage, this composition did not show any antimicrobial effect against all the test strains of gram-negative microorganisms and <em>C. albicans</em> ATCC 885-653. The composition of 1.0% aqueous solutions of unmodified nisin and amlodipine after 1 month of observation also maintained a moderate antimicrobial effect against both test strains of gram-positive microorganisms, as well as against <em>E. coli</em> ATCC 25922 and <em>P. aeruginosa</em> ATCC 27853. After 2 months of observation, the antimicrobial effect of the double composition of unmodified nisin with amlodipine against <em>S. aureus</em> ATCC 25923, <em>B. subtilis</em> ATCC 6633 and <em>E. coli </em>ATCC 25922 continued to decrease within the moderate range. As for the rest of the test strains of gram-negative microorganisms and <em>C. albicans</em> ATCC 885-653, no antimicrobial effect was observed after 2 months of observation. The triple combination of 1.0% aqueous solutions of unmodified nisin, diclofenac sodium and amlodipine maintained moderate antimicrobial activity against both gram-positive microorganisms during all 3 months of observation, although the effect slightly decreased during the observation period. Among Gram-negative microorganisms, the slowest decrease in susceptibility to the triple combination of unmodified tetnisin with diclofenac sodium and amlodipine was observed in the test strain <em>E. coli</em> ATCC 25922. The ternary combination of 1.0% aqueous solutions of unmodified nisin, diclofenac sodium and amlodipine maintained moderate antimicrobial activity against both gram-positive microorganisms during all 3 months of observation, although the effect slightly decreased during the observation period. After storage for 1 month, the antimicrobial activity of the double formulations of acetylated nisin with both diclofenac sodium and amlodipine against all the studied reference test strains remained almost at the same level, but during further storage, the level of their antimicrobial effect gradually decreased. The antimicrobial effect of the ternary composition of acetylated nisin with diclofenac sodium and amlodipine decreased from high to moderate against <em>S. aureus</em> ATCC 25923 after 1 month of storage, and against <em>B. subtilis</em> ATCC 6633 - after 2 months. With further storage for 3 months, the level of antimicrobial effect of the triple composition of acetylated nisin with diclofenac sodium and amlodipine slowly decreased within the moderate range. For all the test strains of gram-negative microorganisms studied, the antimicrobial effect of the ternary composition of acetylated nisin with diclofenac and amlodipine remained moderate up to 2 months of observation and decreased to weak after 3 months of storage. <strong>Conclusion. </strong>Thus, according to the results of studying the stability of the antimicrobial effect of compositions based on unmodified and acetylated nisin with diclofenac sodium and amlodipine by keeping them under normal conditions in real time for 3 months, a decrease in their antimicrobial effect was found in relation to all the studied reference strains of microorganisms, while the antimicrobial effect of compositions with acetylated nisin decreased somewhat more slowly than with unmodified nisin. Taking into account the results obtained, it is advisable to use components in pharmaceutical compositions aimed at improving the stability of the antimicrobial properties of pharmaceutical compositions of nisin with resistance inhibitors.</p> <p><strong>Key words:</strong> stability of antimicrobial effect, nisin, acetylated nisin, diclofenac sodium, amlodipine, pharmaceutical compositions, microorganisms</p> <p>&nbsp;</p> Tetyana Osolodchenko Iryna Andreeva Artur Martynov Nadiya Zavada Olena Batrak Iryna Ryabova Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 40 46 10.5281/zenodo.13819951 Preclinical studies of the combined ointment based on walnut extract https://journals.uran.ua/ami/article/view/308753 <p>Currently, the treatment of wound infection and its complications is an urgent problem in medicine. Gunshot and shrapnel injuries are characterized by the greatest severity, multiple, combined and multi-component nature of damage. In this regard, much attention is paid to the development and use of antimicrobial agents for the local treatment of purulent-inflammatory processes, primarily based on plant extracts. The advantage of using medicinal plants and phytopreparations in medical practice is their low toxicity and absence of pronounced side effects. A combined medicinal product for the treatment of wound infection in the form of an ointment based on plant raw materials - extracts of black walnut or walnut, antiseptic miramistin and anesthetic lidocaine hydrochloride has been developed at the State University "IMI NAMN of Ukraine". It is known that the toxicity, as well as the biological activity, of walnut extracts is due to their main active component - juglone. In vitro experiments have shown that juglone has a cytotoxic effect, causing the destruction of cell membranes. At the same time, when applied to the skin, juglon is poorly absorbed, so its systemic effects and manifestations of toxicity are unlikely. In this regard, a study of the harmlessness of the developed composition of the ointment with walnut carbonic acid extract (EGV) was conducted. The study was performed on outbred white rats in accordance with methodological recommendations for the experimental study of the toxic effect of potential medicinal products. It was established that the combined ointment based on walnut extract with carbonic acid does not have a negative effect on the body of experimental animals, does not affect biochemical and hematological indicators, when used once or chronically. In addition, the ointment does not have a local irritating effect when applied chronically. Thus, the obtained results of the harmlessness study allow us to conclude that the combined ointment based on carbonic walnut extract is completely safe in terms of acute and chronic toxicity, as well as local irritant effect.</p> <p><strong>Key words</strong>: walnut carbonicum extract, acute toxicity, chronic toxicity, local irritant effect.</p> Ivan Mozhaiev Tetyana Nosalska Inna Dovha Victoria Yevsiukova Victor Kazmirchuk Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 47 49 10.5281/zenodo.13819889 (Information letter) Method of determining the frequency of pertussis infections by their serological prevalence https://journals.uran.ua/ami/article/view/311835 <p>The interpretation of serological values ​​of PT-IgG MO/ml is proposed: 5 MO/ml – limit titer; 50–99 MO/ml - infection lasting for the remaining 3-5 years; ≥100 MO/ml – infection for the rest of the year. The use of this method makes it possible to increase the established frequency of pertussis infections beyond their serological spread, which means that populations will require additional pacification, preventive treatment and dynamic care, in turn; I will be able to develop more effective strategies for their control.</p> <p><strong>Keywords</strong>: pertussis infections, serological prevalence.</p> Andrii Volianskyi Maia Smilyanska Tetiana Didorenko Halyna Bolshakova Olha Holubka Copyright (c) 2024 Annals of Mechnikov's Institute https://creativecommons.org/licenses/by/4.0 2024-09-21 2024-09-21 3 50 51 10.5281/zenodo.13819861