Perm State Pharmaceutical Academy

The article focuses on establishing risks of side reactions caused by using aqueous extract of Picea abies mega-strobiles for three months and provides histological results for internal organs obtained in an experiment. The aim of this study was to establish safety of aqueous extract of Picea abies mega-strobiles by estimating its effect on various organs and tissues of experimental animals in a sub-chronic toxicity test. Picea abies mega-strobiles were harvested on the territory of the Perm region in the Russian Federation in a fir tree forest with green moss and grass cover. Dry aqueous extract was obtained according to the original patented method. An experiment was conducted using white outbred Wistar rats of both sexes. The analyzed extract was administered daily for three months. Distilled water was administered in the control animal group as equivalent stress exposure. The element structure of bone samples was established using x-ray fluorescence with an energy-dispersion x-ray fluorescent spectrometer. Heart, kidneys, stomach and small intestine were extracted from the experimental animals for microscopic examination. Chronic oral administration of aqueous extract of Picea abies mega-strobiles into healthy inflammation-free rats did not cause any changes in their behavior, mucosa or fur as confirmed by comparative analysis of the indicators between the test and control animal groups, the latter not exposed to the extract. Histology of the gastrointestinal organs (stomach and small intestine) did not find any differences between the test and control groups; no differences were found between male and female rats in the test group either. The experiment did not establish any toxic effects produced on the heart or kidneys by aqueous extract of Picea abies mega-strobiles. The results obtained by analyzing rats’ stomach and small intestine as well as heart and kidneys indicate absence of any significant differences between the test and control group. The analysis of the bone element structure revealed a trend for growing levels of calcium and phosphor in rat bones in the test group (exposed to aqueous extract of Picea abies mega-strobiles). These findings make it possible to conclude that use of aqueous extract of Picea abies mega-strobiles at the dose of 12 mg/kg for 12 weeks did not cause any significant impairment either in mucosa, fur, or internal organs of experimental animals.

Introduction. One of the most pressing areas of modern pharmacy is the creation of highly effective and safe drugs. The search for antitumor agents, driven by the increasing incidence of cancer, is focused on obtaining targeted drugs. 2-aminopyrrole derivatives synthesised at the Perm State Pharmaceutical Academy have demonstrated high cytostatic activity due to the activation of the mechanism of tumour cell apoptosis in the M phase. Preclinical studies should include toxicometry and determination of the pharmacokinetic parameters of the most active compound, 2-ANPC. Aim. To study acute toxicity in experiments on mice and rats and the pharmacokinetic parameters of 2-ANPC after a single administration to Wistar line rats. Materials and methods. The assessment of acute toxicity upon oral administration, with LD 50 calculation using Finney's probit analysis method, was conducted in experiments on white non-linear mice and Wistar line rats. The pharmacokinetic parameters of 2-ANPC were studied in male Wistar line rats after administration of the compound per os. A validated method based on high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was used for the quantitative determination of 2-ANPC in the blood plasma of animals. Results and discussion. The LD 50 of the compound after a single oral administration was determined to be 4434 mg/kg for mice and 1547 mg/kg for rats. The time to reach the maximum concentration of 2-ANPC in rats after a single administration of 150 mg/kg is 2,90 ± 0,32 h, and the half-life of the compound from the body is 4,50 ± 0,49 h. The calculated apparent volume of distribution, which significantly exceeds the anatomical volume, indicates the predominant localisation of the substance in the extravascular space. Conclusion. The study of acute toxicity in mice established that 2-ANPK belongs to toxicity class 4 (low-toxicity substances) according to the Hodge and Sterner classification and to hazard class 5 of chemical products based on their impact on the body. In an experiment on rats, the pharmacokinetic parameters of 2-ANPC after oral administration were evaluated. The data obtained show the potential for developing an oral dosage form based on this new 2-aminopyrrole derivative with proven antitumor activity.

В статье рассматривается специфика ономастического пространства в романе Дж. Джойса «Поминки по Финнегану». Актуальность темы обусловлена необходимостью поиска переводческих стратегий для передачи сложной ономастической игры и интертекстуальных культурных кодов в модернистском произведении писателя. В ходе исследования применяются метод сплошной выборки, описательный, сопоставительный, контекстуальный и интертекстуальный анализы. Раскрывается специфика игровой техники писателя на базе антропонимов. Выделен ряд приемов кодирования имени собственного Анна Ливия Плюрабелль, усложняющих процесс восприятия и перевода в связи с вариативностью возможных трактовок (частичная / полная аббревиация, аллитерационная эмфаза инициалов имени, использование иноязычных включений и др.). Проанализированы частичные и полные переводы «Поминок по Финнегану» на русский (А. Сергеев, А. Волохонский, С. Диваков, О. Брагина, А. Рене), немецкий (У. Блюменбах и Р. Маркнер, К. Райхерт, Г. Бек, Д. Штюндель, И. Горн, Р. Венингер, Г. Волльшлегер, К. Яуслин, Ф. Ратьен) и испанский (М. Забалой) языки. Изучен арсенал переводческих решений, выделен ряд закономерностей. Отмечено, что во всех случаях переводчики вынуждены применять стратегию «деформации» языка перевода для отображения «языковых аномалий» Дж. Джойса. Сделаны выводы, что родство немецкого и английского языков позволяет в большей степени (в сравнении с русским) сохранить в переводе словообразовательные и звуковые особенности закодированного антропонима. This paper aims to explore certain features of Joyce’s onomastic space in Finnegans Wake. The relevance stems from the need to identify translation strategies for rendering the complex onomastic wordplay and intertextual cultural codes in James Joyce’s modernist novel. The study employs the continuous sampling method, descriptive, comparative, contextual, and intertextual analyses. A set of the author’s experimental techniques based on language games involving proper names is analyzed. The encoding of anthroponym Anna Livia Plurabelleis described in detail, underlining its ability to complicate perception and translation due to the diversity of possible interpretations. Fragmentary and complete versions of Finnegans Wake in Russian (by A. Sergeev, A. Volokhonsky, S. Divakov, O. Bragina, A. Rene),German (U. Blumenbach and R. Markner, K. Reichert, H. Beck, D. Stündel, I. Horn, K. Jauslin, H. Wollschläger, R. Weninger, F. Rathjen), and Spanish (M. Zabaloy) are compared. The translation strategies are explored and regularities in translation methods are figured out. To render J. Joyce’s onomastic language games translators are compelled to “deform” the target language. It is concluded that the structural similarities and differences of the source and the target languages influence the extent to which translators can transferword-formation and phonetic features of the encoded anthroponym, making, for example, German a more appropriate “tool” than Russian for translating the novel.

Introducrion. The search for new agents with antimicrobial activity is urgent due to the emergence of resistant pathogens not sensitive to existing antimicrobial drugs. New compounds with antimicrobial properties allow for a wider range of therapeutic options, the discovery of compounds with novel mechanisms of action, and the elucidation of the structure-activity relationships of the compounds being studied. The search for new lead com-pounds among substituted 4-(azol-1-ylmethyl)-1,3-dioxolanes is of interest, as compounds exhibiting fungicidal and antimycobacterial properties have been discovered among members of this subclass. The aim of the work is to study of the antimicrobial activity of substituted 4-(azol-1-ylmethyl)-1,3-dioxolanes. Materials and methods. The 4-(azol-1-ylmethyl)-1,3-dioxolanes under study were obtained at Moscow Institute of Physics and Technology and the Mendeleyev University of Chemical Technology. Their antimicrobial properties were tested against E. coli ATCC 8379, S. aureus ATCC 6538 and C. albicans РКПГY401 using two-fold serial dilutions in liquid nutrient media followed by plating on solid nutrient media. The bactericidal antibiotics van-comycin and doxycycline and the antifungal agent fluconazole were selected as reference agents. Results. A study of antimicrobial activity showed that 4-(azol-1-ylmethyl)-1,3-dioxolanes have low activity against E. coli. The introduction of a halo-phenyl moiety instead of an alkylphenyl moiety into the 2-position of the dioxolane ring, the replacement of the alkyl substituent in the 2-position of the dioxolane ring with a benzyl one, in particular chlorobenzyl (I, III), as well as the transition from triazole-containing (IV-VIII) to imidazole-containing de-rivatives (I-III) significantly improves the bactericidal properties against S. aureus and the fungicidal properties against C. albicans. The MIC values for 4 imidazolylmethyl-1,3-dioxolanes I and III against S. aureus are 31 μg/ml, and against C. albicans 31 and 15 μg/ml, respectively, which brings the anti-microbial properties of the target compounds closer to the reference compounds doxycycline and fluconazole. Conclusions. The studied 4-(azol-1-ylmethyl)-1,3-dioxolanes demonstrated activity against S. aureus and C. albicans. A relationship between the struc-ture and antimicrobial activity of the compounds was revealed: 2-chlorobenzyl-2-halophenyl-4-(imidazol-1-ylmethyl)-1,3-dioxolanes exhibited the highest activity, with MIC values two times lower than those of the reference doxycycline and four times lower than those of fluconazole. Further research is aimed at identifying new, more active antimicrobial agents.

Objective. To study the effect of mineral water of Klyuchi Resort therapeutic and table mineral water on the intestinal microbiome of white mice with experimental dysbiosis. We have previously demonstrated the bacteriotropic effect of this mineral water on the obligate intestinal microbiota in vitro. The present study investigated the effect of this mineral water on the correction of experimental dysbiosis in laboratory animals. Materials and methods. Experiments were performed on 42 outbred male white mice. Dysbiosis was induced by oral administration of a gentamicin solution for 8 days. The test group of animals received mineral water, while the control group received boiled tap water. The qualitative and quantitative composition of the animals' intestinal microbiota was assessed dynamically using a classical bacteriological method. Reference points were baseline values before antibiotic administration, after the antibiotic course, and on the 14th and 28th days of mineral water intake. Results. Dysbiosis was characterized primarily by a significant decrease in the titers of Lactobacillus and Bifidobacterium species and the appearance of Klebsiella and Proteus in high concentrations. After two weeks of mineral water administration, the test group showed a tendency toward normalization of the intestinal microbiota composition. These positive changes increased over time. After 28 days, lactobacilli count in the test group of animals returned to initial values. Klebsiella spp. and Proteus spp. were not detected. Conclusions. Mineral water of Klyuchi Resort contributed to the normalization of the qualitative and quantitative composition of the intestinal microbiota in laboratory animals with experimental dysbiosis.