Вступ. Антисептичні засоби для рук та антибактеріальні вологі серветки є одними з основних (після миття рук з милом під проточною водою) методів неспецифічної профілактики інфекцій з фекально-оральним та повітряним механізмами передачі, зокрема COVID-19. ВООЗ та МОЗ України в період пандемії рекомендують регулярне застосування антисептиків для рук, проте в Україні, на відміну від країн ЄС, не сформована належна нормативно-правова база, котра б забезпечувала якісний контроль ефективності загальнодоступних антисептиків для рук щодо протимікробної чи противірусної дії. Натомість МОЗ України на час пандемії вірусу SARS-CoV-2 спростило реєстрацію нових дезінфекційних засобів, що, разом з підвищеним попитом на них, збільшує ймовірність потрапляння на ринок антисептичних засобів з неперевіреною ефективністю.

Метою роботи було визначити рівень протимікробної та протигрибкової дії наявних на ринку України антисептиків для рук та вологих антибактеріальних серветок.

Методи. Було протестовано 36 зразків, з них 19 (52.8%) антибактеріальних вологих серветок та 17 (47.2%) антисептиків для рук, в тому числі 5 (13.9%) гелевих антисептиків та 12 (33.3%) спреєвих антисептиків для рук, таких як:

  • вологі серветки з позначкою «антибактеріальні» «Naturelle», «Smile з спиртом», «Smile baby», «Smile з пантенолом», «Smile з подорожником», «Viva Fruts», «Zeffir», «Глянц», «Chicolino», «Green Way», «Lili», «Novax», «Ozon», «Ruta», «Superfresh», «Supero», «Добрий Дотик», «Сніжна Панда», «Siela»;
  • спреєві антисептики «Altamed», «Colour intense», «ProEcolek», «Green Way», «Lucky Day», «Manorm», «Wash Your Body», «Антисептична рідина», «Аргенвіт», «Аніоспрей», «Срібна вода», «Цілитель»;
  • гелеві антисептики «Vital Charm», «Wash Your Body», «Доктор Біокон», «Aromat», «Manorm».

Протимікробну та протигрибкову дію визначали методом дифузії в агар (метод «колодязів»), використовуючи референс-культури та клінічні ізоляти мікроорганізмів, виділених від пацієнтів з інфекціями пов’язаними з наданням медичної допомоги, такі як: Escherichia coli АТСС 25922; Staphylococcus aureus АТСС 26923 (F-49); Candida albicans АТСС 885/653;  Pseudomonas aeruginosa ATCC 27853 (F-51, Escherichia coli №5; Candida albicans №60; Candida non-albicans №67; Raoultella terrigena №1; Staphylococcus lentus № 19; Brevundimonas vesicularis №111; Citrobacter sedlakii №37; Pseudomonas aeruginosa №13; Enterococcus spp. №161; Aerococcus viridans №26.

Результати. Серед досліджених антисептиків та вологих антибактеріальних серветок 36.1% (n=13) не мали декларованої мінімальної протимікробної активності, в тому числі серед гелевих антисептиків  60.0%  (n=3) та серед спреєвих антисептиків 50.0% (n=6). Тобто, кожен другий спреєвий та гелевий антисептик не може бути використаний з метою неспецифічної профілактики інфекційних хвороб. Щодо вологих антибактеріальних серветок, то 21.0% (n=4) з них проявили недостатню протимікробну дію.

Висновок. Правильне миття рук під протічною водою з милом залишається одним із основних методів неспецифічної профілактики хвороб із повітряним та фекально-оральним механізмами передачі. Враховуючи отримані результати, для додаткової гігієнічної обробки рук краще користуватися антисептиками та протимікробними вологими серветками відомих виробників, придбаними в аптечних мережах, надаючи перевагу спиртовмісним гелевим антисептикам.

Keywords: 

2-thioxo-4-thiazolidinones, indolecarbaldehydes, synthesis, cellular immunity, phagocytosis, immunotropic activity, leukocytes, guinea pigs

Abstract

The aim. To study the cell immunity status under influence of 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-propionic acid, as a prominent 4-thiazolidinone derivative and a class of biologically active compounds with polypharmacological properties.

Materials and methods. Experimental method on the model of laboratory animals (guinea pigs); intradermal allergy tests; relative and absolute content in the peripheral blood of T- and B-lymphocytes subpopulations; hematological indexies: index of the ratio of lymphocytes and monocytes, index of the ratio of neutrophils and monocytes, index of the ratio of neutrophils and eosinophils, phagocytic index, phagocytic number; ELISA; organic synthesis; pharmacological screening.

Results. The effect of 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-propionic acid has antifungal properties and affect cellular component of immunity in vivo in the guinea pigs model. There are no changes in the skin of guinea pigs during and after chemical applications of the skin and after intradermal tests. The compound stimulate the immune cells, in particular the lymphocyte (increase in the absolute number of CD3 T-lymphocytes by 21.46 % and the absolute number of CD8 T-suppressors by 27.15 %), but with a selective inhibitory effect on certain units (decrease the relative number of NK cells CD16 by 11.57 % and B-lymphocytes CD22 by 23.08 %). There was an increase in the activity of the macrophage phagocytic system (increase in PN by 439.87 % and PI by 62.73 % at 120 minutes), which indicates the reliability of the absorbing function of phagocytes, but with a decrease in their ability to endocytosis (PCI decreased significantly by 78,72 %).

Conclusions. Synthesized 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-propionic acid has a selective activating effect on certain parts of cellular immunity and on phagocytic activity. Derivate influence on the phagocytic activity of neutrophils is ambiguous, and the effect of the compound directed to the cellular part of the immune system does not cause cellular immunodeficiency. The studied derivative is promising for further study of the drug-like molecule with antifungal and antitumor effects

In the Lviv region, cases of healthcare-associated infections (HAIs) in children occur, but are practically not registered. For the period 2019–2021, not a single case was registered. Purpose — to identify and compare the species composition of potential HAIs pathogens in children and adults in Lviv hospitals. Materials and methods. Material for the study was collected from children from various biological niches who were undergoing inpatient treatment in Lviv hospitals. Identification was carried out using MIKRO-LA-TEST kits manufactured by Erba Lachema. Antibiotic susceptibility was determined according to EUCAST recommendations. Results. Among the isolated gram-positive microbiota that meets the criteria of HAIs, enterococci were most often detected in adults (30,8%), among children (from 0 to 17 years) — in 35,4% of cases. Staphylococcus epidermidis was detected in 21,5% from children's patients, as the causative agent of the purulent-septic process, while in adults – 27,2%. A significant part of S. aureus cultures (63,6%) isolated from children was resistant to amoxicillin (among adults — 56,5%), ceftazidime (54,5%) and cefuroxime (45,4%). Among adult patients, the percentage of isolated resistant strains to ceftriaxone (65,2%), cefotaxime (52,2%), cefepime (87,0%) was significantly higher compared to such indicators in children – 9,1%, 18,2% and 36,4%. The antibiotic ceftizoxime, widely used in recent years in the treatment of children, was not effective in 45,5% of cases. Conclusions. Despite the low level of registration of HAIs in children, this problem exists. The number of resistant strains is increasing. The sensitivity of strains to antibiotics isolated in children and adults differs significantly, so general recommendations may not be effective. The role of the clinical microbiologist and epidemiologist is extremely important for effective infection control and quality empiric antibiotic therapy in individual healthcare settings. The research was carried out in accordance with the standarts of bioethics, approved by the ethics committee of the Danylo Halytskyi LNMU. The informed consent of the child's parents and the patient was obtained for the description of the clinical case. © 2023 Group of Companies Med Expert, LLC. All rights reserved.

Author keywords

children’s hospital; gram-positive microbiota; HAIs; hospital infection

UDC 547-327:547.821:54.057

The aim. The combination in one molecule of pharmacophore fragments of thieno[2,3-d]pyrimidine-4-carboxylic acids with the fragments of 2-or 4-aminopyrimidine by peptide coupling promoted acylation in order to develop the new drug-like molecules with antimicrobial activity. Materials and methods. The molecular docking studies were performed with the AutoDock Vina and AutoDock-Tools 1.5.6 programs; TrmD Pseudomonas aeruginosa PDB ID – 5ZHN was used as the protein target. Synthetic methods of peptide coupling were used. 1H and 13C NMR spectra were recorded with a Varian-400 spectrometer at 400 MHz and Bruker Avance DRX 500 device at 500 MHz and 125 MHz in DMSO-d6 as a solvent, using TMS as the internal standard. LC-MS analysis of the compounds was carried out with Agilent 1100 HPLC з with at-mospheric pressure chemical ionization (APCI). The studied derivates were tested in vitro for their antibacterial and anti-fungal activities using agar diffusion and serial dilutions resazurin-based microdilution assays (RBMA). Results and discussion. By the combination of the pharmacophore fragments of thieno[2,3-d]pyrimidine-4-carboxylic acids with the fragments of 2-of 4-aminopyrimidine, the combinatorial library of amides was constructed. For this library of compounds, the potential of antimicrobial activity was revealed using docking studies to the TrmD enzyme isolated from P. aeruginosa. The peptide coupling promoted by 1,1’-carbonyldiimidazole was found to be effective for the synthesis of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acids, and it allowed to combine these phar-macophores in one molecule. The results of antimicrobial activity study revealed the broad spectrum of antimicrobial activity for N-(pyridin-4-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4-carboxamide (2g), while 5,6-di-methyl-N-(6-methylpyridin-2-yl)thieno[2,3-d]pyrimidine-4-carboxamide (2c) showed the best MIC value against the reference strain of Pseudomonas aeruginosa ATCC 10145. N-(6-Methylpyridin-2-yl)-5,6,7,8-tetrahydro[1]benzothien-o[2,3-d]pyrimidine-4-carboxamide (2h) was also found to be active against Pseudomonas aeruginosa. Conclusions. An effective method for the synthesis of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acid has been developed. The amides molecular docking method showed their ability to inhibit TrmD enzyme isolated from P. aeruginosa; the further in vitro studies of the compounds showed the rationality of the further studies of the derivatives with 2-ami-no-6-methylpyridine in amide substituent because this fragment favoured the selectivity against Pseudomonas aeruginosa. © The Author(s) 2023.

Author keywords

amides; antimicrobials; coupling; docking study; thieno[2, 3-d]pyrimidine

UDC 615.322:615.451.1

Actuality. The widespread use of herbal drugs with anti-inflammatory and nephroprotective properties stimulates the search for new active biological substances. Of particular interest are plants from the Ranunculaceae family, especially Anemone nemorosa, which contains a range of potentially bioactive components such as anemonin, protoanemonin, and others. Understanding the acute toxicity, anti-inflammatory, and hypoazotemic activity of Anemone nemorosa extracts opens possibilities for the development of new therapeutic agents based on this plant. Materials and methods. Ethanol extracts were obtained from the aerial parts of Anemone nemorosa harvested during the flowering period. The study included the examination of oral acute toxicity conducted on Wistar rats over 14 days, anti-inflammatory activity using the carrageenan-induced paw edema method in Wistar rats, and hypoazotemic activity on models of healthy and acute renal failure in Wistar rats. Results. The extracts showed no acute toxicity at the administered dose. It was established that the oral administration of the extracts is non-toxic up to a dose of 200 mg/kg body weight. The anti-inflammatory tests did not reveal significant therapeutic effects. However, the hypoazotemic tests demonstrated a reduction in blood urea and creatinine levels, and an increase in these indicators in urine, especially under conditions of acute renal failure, indicating a strong diuretic effect of the extracts. Conclusions. The Anemone nemorosa extracts exhibited strong hypoazotemic and diuretic activity, which may be beneficial for the treatment of kidney diseases. The absence of anti-inflammatory activity requires further analysis and possible modification of extraction methods. The study results support the potential use of this plant in developing new nephroprotective phytopreparations. © O. Khropot, Yu. Konechnyi, G. Lavryk, I. Tymchuk, O. Pinyazhko, V. Lubenets, R. Konechna.

Author keywords

Acute toxicity; Anemone nemorosa; Anti-inflammatory activity; Extracts; Hypoazotemic activity; Ranunculacea