ANTIOXIDANT, METABOLIC AND ANTITUMOR ACTIVITY OF TRITERPENOIDS COMBINATION WITH CYTOSTATICS

Objective: To study the effect of betulin derivatives combination with 5-fluorouracil or hydrazine sulfate on the ROS generation, the SOD and LDH activity using rat blood, as well as the effect of combination drugs on Ehrlich carcinoma in experiments on mice. Methods: We used a chemiluminescence technique to study the ROS generation, and spectrophotometry to determine the MDA level and the SOD and LDH activity. The model of transplanted Ehrlich ascites carcinoma was investigated on mice using a cytological analysis of ascitic fluid cells according to Pappenheim`s method. Results: In vitro experiments on rat blood at the doses of 2, 5 and 10 μg per ml revealed the dose-dependent effect of combination drugs on the antioxidant properties. In plasma, the ROS generation and the MDA level increased by 10-300% in comparison with control at the doses of 5 and 10 μg per ml only. Still, the SOD and LDH activity in general increased by 10-130% in comparison with control under the action of the studied combination drugs. The study on mice showed the effectiveness of a combination of triterpenoids and cytostatics in Ehrlich ascites carcinoma therapy. The state and behavior of the animals improved, the volume of ascites fluid decreased by 40-50% after treatment for 10 d. Conclusion: The combination of betulin derivatives with cytostatics can be used as antitumor drugs in Ehrlich ascites carcinoma therapy that is due to metabolic plasticity, increased ROS generation in enhanced antioxidant enzyme protection

THE IMPROVEMENT OF BETULIN-3, 28-DIPHOSPHATE WATER-SOLUBILITY BY COMPLEXATION WITH AMINES–MEGLUMINE AND XYMEDON

Objective: To study betulin-3,28-diphosphate (BDP) water solubility improved by forming salt complexes with hydrophilic amino alcohols: meglumine as acidosis corrector and xymedon as the water-soluble antioxidant. Methods: We used 13C-, 31P-NMR, UV-spectroscopy and potentiometric titration to study the BDP-amine salt complexes formation and their solubility using HPLC-analysis. Results: The participation of xymedon in the proton transfer reaction with BDP in aqueous solutions was confirmed by the bathochromic shift of the carbonyl band from 299.1 nm to 304.2 nm, and by a hyperchromic effect (molar extinction ε from 8508 to 10 441 l·mol-1·cm-1) in UV-spectra. BDP complexation with meglumine was estimated by UV-spectral molar ratio method at 256 nm. Molar ratio of BDP-amine complexes (1:4) was proved by 31P-NMR. The chemical shift of phosphorus at C-3 atom of BDP (δ =-0.58 ppm) changed to+3.39 ppm, and at C-28 atom (δ =+0.28 ppm)–to+4.60 ppm. BDP solubility increased 100-600 fold according to HPLC-analysis. Conclusion: BDP interaction with amine in an aqueous solution was shown to proceed via a proton transfer due to relatively weak forces such as London forces, hydrogen bonding, electrostatic and hydrophobic interactions. In general, the formation of BDP salt complexes with amines in solution determines BDP water solubility. Water-soluble BDP enables to develop hydrophilic dosage forms

Influence of Temperature on the Thermal Properties of the Core Material - the Coefficient of Temperature Conductivity, Specific Heat Capacity, Thermal Conductivity

The absorption of heat by rocks is accompanied by an increase in the kinetic energy of molecules and atoms and is recorded by a change in rock temperature. The thermal properties of rocks characterize the ability to transfer and absorb heat and change their size when the temperature rises. The main thermal properties of rocks are thermal conductivity, heat capacity, linear thermal expansion, and thermal volumetric expansion. In this paper, the influence of temperature effects on the thermal properties of reservoirs – the coefficient of temperature conductivity, specific heat capacity, and thermal conductivity is studied using the samples of oil-saturated reservoirs from the good number 19Bp of the Upper Uplift of Sotnikovsky deposit. The dependence of the thermal properties of the core material on temperature was revealed using a number of laboratory experiments. The results of these studies contribute to improving the reliability of data on the relationship of thermal properties with other physical properties of oil-saturated reservoirs and can be used to improve the efficiency of the development of fields of super-viscous oil.&nbsp

BETULIN-3, 28-DIPHOSPHATE SALT COMPLEXES WITH AMINES AND THEIR ANTIOXIDANT ACTIVITY

Objective: Studies of composition, stability and antioxidant properties of the betulin-3, 28-diphosphate complexes with dopamine and trisamine.Methods: The betulin-3, 28-diphosphate (BDP) interaction with amines in a water-alcohol medium was studied by using spectral methods and potentiometric titration. Biochemical indexes such as catalase, superoxide dismutase (SOD), lactate dehydrogenase (LDH) activities and malondialdehyde (MDA) level were estimated in experiments on rats.Results: BDP was synthesized using betulin by POCl3 treatment in the presence of pyridine in dioxane. The complexation of BDP with amines was confirmed by the 31P-NMR and FTIR-spectral data. The stoichiometry of BDP-dopamine complexes was equal to 2:1 and 4:1 and its complexes with trisamine were produced in the ratio 1:1 in a water-alcohol medium. The conditional stability constant К′st of the BDP-trisamine complex is 1130±55 mol∙l-1. BDP-Tris complex improved SOD activity up to 30% and up to 105% in the presence of cytostatic-hydrazine sulfate. The MDA level in erythrocytes decreased up to 57% and in combination with cytostatics (5-fluorouracil and hydrazine sulfate)-up to 11-14%. The catalase activity increased by 44-94% and MDA level in erythrocytes decreased by 22-53% under the action BDP-DA complexes that depends on the dose.Conclusion: The BDP forms stable complexes with trisamine and dopamine that make it possible to use this compound as a component of drug delivery system for high toxicity cytostatics and for readily oxidized catecholamines. It has been shown that both its complexes with amines and the combination with cytostatics enhanced antioxidant activity in an experiment in vitro

ОТРАЖЕНИЕ СОЦИАЛЬНЫХ ОЖИДАНИЙ И ПРАВИЛ «ФЕМИННОСТИ» И «МАСКУЛИННОСТИ» В АНГЛОЯЗЫЧНОЙ ПОДРОСТКОВОЙ ЛИТЕРАТУРЕ (НА МАТЕРИАЛЕ ПАРАЛЛЕЛЬНЫХ КОРПУСОВ ХУДОЖЕСТВЕННЫХ ТЕКСТОВ)

Purpose. The paper is given to the topic of the social rules and expectations as reflected in the young adult literature, which is among the prior interests due to contemporary world population mobility. The subject for analysis is represented by fiction texts, which compose the parallel corpora, in English and Russian. The authors aim at describing specific language means used to display social rules and expectations in the fiction parallel texts in the English and Russian languages.Methodology. The methodology of the research is based on the interdisciplinary approach to studying social interactions that includes cognitive and discourse analysis. This embraces the corpus and comparative analyses of parallel English as well as Russian fiction texts.Results. Considering fiction texts simultaneously as cultural artefacts and discourse cases, their didactic nature signifying its part in forming, reproducing and codifying social expectancies and rules as mutual experience, gives the researcher an opportunity to identify specific linguistic units and features that express expectances and rules of gender interaction. Corpora and comparative analyses help to identify differences of English and Russian linguistic means that are used to denote participants of gender interaction. The abovementioned differences include linguistic and discourse features influenced by the cognitive mechanisms. They are as follows: thesaurus environment, semantic similarity and collocation capacity of units.Practical application. The results of the research can be used in L2 teaching to promote sociocultural competence.Цель. Статья посвящена актуальной в условиях современной мировой мобильности теме отражения социальных ожиданий и правил «феминности/маскулинности» в англоязычной подростковой литературе. Предметом анализа выступают тексты художественных произведений на английском и русском языках, составляющие параллельные корпусы исследования. Авторы ставят целью раскрыть специфику языковых способов отражения социальных ожиданий и правил «феминности/маскулинности» в английском и русском языках на материале параллельных текстов.Методология проведения работы. В основе методологии исследования лежит когнитивно-дискурсивный подход к исследованию параллельных корпусов художественных текстов с использованием корпусного анализа и последующего сравнительного анализа параллельных текстов.Результаты. Изучение художественного текста одновременно как культурного артефакта и частного случая дискурса, дидактический характер которого исследования определяет его роль в формировании и репродукции, закреплении и передаче социальных установок и правил как культурного опыта, позволяет выявить специфику языкового выражения социальных правил и ожиданий, применяемых к гендерному взаимодействию. Проведенный сравнительный анализ позволяет выявить различия способов отражения этих установок, выражающиеся в специфике тезаурусного окружения и комбинаторики языковых единиц, обозначающих участников гендерных отношений.Область применения результатов. Результаты исследования могут быть применены в обучении иностранному языку, формировании социокультурной компетенции лиц, изучающих английский как иностранный язык

SPIRIT and CONSORT extensions for early phase dose-finding clinical trials:the DEFINE (DosE FIndiNg Extensions) study protocol

Introduction Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements. Methods and analysis A methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions. Ethics and dissemination This project was approved by ICR’s Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites