Antimicrobial resistance in clinical <I>Escherichia coli</I> isolates obtained from animals

The article presents data on the phenotypic and genotypic characteristics of antimicriobial resistance in Escherichia coli clinical isolates recovered from bovine microbiota (secretions from mammary glands, cervical swabs). 127 Escherichia coli isolates were studied, i.e. 44 from mammary glands secretions and 83 from cervical swabs. Disk diffusion method was used to study antimicrobial resistance of the cultures; minimum inhibitory concentrations of antimicrobials were determined in a serial dilution method; resistance genes were detected by polymerase chain reaction. The carried out research demonstrates a wide distribution of the isolates belonging to the phenotype resistant to ansamycins (rifampicin), semi-synthetic penicillins (ampicillin and amoxicillin), tetracyclines (doxycycline). The isolates showed a lower level of resistance to macrolides (azithromycin), amphenicols (levomycetin) and aminoglycosides (tobramycin). It was found that Escherichia coli clinical isolates are sensitive to third-generation cephalosporins and fluoroquinolone antimicrobials. However, since 28.46% of cultures demonstrate intermediate resistance to third-generation cephalosporins and 49.02% of Escherichia coli DNA samples isolated from mammal gland secretions had blaDHA gene associated with resistance to this group of antimicrobials, these antimicrobials could be hardly recommended as antibiotics of choice. Absence of VIM carbapenemase-encoding gene in the DNA of the recovered isolates and a low level of phenotypic resistance (10.22% of isolates from cervical swabs) can be one of the reasons for recommending first-line carbapenems as antibiotics of choice to treat animal diseases associated with Escherichia coli, along with fluoroquinolones as reserve antimicrobials. It was found that the recovered Escherichia coli isolates are more sensitive to combination antibiotics than to mono-antibiotics

The degree of restoration of the soil properties developed under the fallows in the early stages of succession

At present, the return of fallow lands to agricultural circulation is an important and one of the topical issues of the whole world. Research related to the restoration of soil properties of fallows is of particular value. Therefore, it is necessary to know what processes occur in the vegetation and soil cover of fallows at the different stages of their development, taking into account local natural features. The paper presents the results of a survey of young (up to four years) and middle-aged (up to ten years) fallows of the forest-steppe zone of Western Siberia within the Novosibirsk region. It is established that in the first decade of succession in fallow areas there are two stages of overgrowth, and when analyzing the structure of plant matter, it is shown that the ratio of their fractional composition reflects the general tendency to restore the ecosystem that preceded plowing. Restoration of soil properties under young and middle-aged fallows is much slower. Data of humus content analysis allow us to conclude that its content is somewhat higher in the upper parts of the profile in middle-aged fallows compared to young fallows. The research on soil-physical characteristics and vegetation cover allowed us to note the trends of restoration of the initial state of soils

Anti-Tumour Drugs: Planning Preclinical Efficacy and Safety Studies

The decoding of the DNA structure and development of new molecular methods of its analysis, as well as identification of specific genomic changes responsible for malignant transformation, have become the turning points in elaboration of novel anti-tumour drugs directed against molecular and genetic targets of tumor growth. Transition from empirical screening of agents inhibiting tumour cell proliferation to molecule-targeted analytical methods has raised a number of serious methodological issues regarding preclinical evaluation of novel medicines. The objective of this paper was to analyse general principles and features of preclinical efficacy and safety studies of different classes of modern anti-tumour drugs with a view to improve existing national guidelines. The paper reviews various aspects of preclinical studies of different classes of anti-tumour drugs (small molecule chemotherapy drugs, hormones and hormone antagonists, alkylating agents and antimetabolites, microbial and herbal medicines, as well as monoclonal antibodies). The article explores general principles of studying the drugs’ pharmacological activity in vitro, ex vivo, and in vivo, and evaluating their pharmacokinetic parameters. It describes various methods and models of research, summarises specific aspects of determination of genotoxicity, carcinogenicity, reproductive toxicity, mutagenicity, acute and chronic toxicity of various groups of medicines. It also lists criteria for selecting drug doses for toxicokinetic studies. The need for harmonisation of national requirements for conducting preclinical studies with the European standards entails alignment of terminology and further development of general algorithms for selecting doses and determining the necessary scope of research. The use of biomarkers in preclinical studies will make it possible to exclude inefficient compounds from further research

Противоопухолевые лекарственные препараты: планирование доклинических исследований по оценке эффективности и безопасности

The decoding of the DNA structure and development of new molecular methods of its analysis, as well as identification of specific genomic changes responsible for malignant transformation, have become the turning points in elaboration of novel anti-tumour drugs directed against molecular and genetic targets of tumor growth. Transition from empirical screening of agents inhibiting tumour cell proliferation to molecule-targeted analytical methods has raised a number of serious methodological issues regarding preclinical evaluation of novel medicines. The objective of this paper was to analyse general principles and features of preclinical efficacy and safety studies of different classes of modern anti-tumour drugs with a view to improve existing national guidelines. The paper reviews various aspects of preclinical studies of different classes of anti-tumour drugs (small molecule chemotherapy drugs, hormones and hormone antagonists, alkylating agents and antimetabolites, microbial and herbal medicines, as well as monoclonal antibodies). The article explores general principles of studying the drugs’ pharmacological activity in vitro, ex vivo, and in vivo, and evaluating their pharmacokinetic parameters. It describes various methods and models of research, summarises specific aspects of determination of genotoxicity, carcinogenicity, reproductive toxicity, mutagenicity, acute and chronic toxicity of various groups of medicines. It also lists criteria for selecting drug doses for toxicokinetic studies. The need for harmonisation of national requirements for conducting preclinical studies with the European standards entails alignment of terminology and further development of general algorithms for selecting doses and determining the necessary scope of research. The use of biomarkers in preclinical studies will make it possible to exclude inefficient compounds from further research.Расшифровка структуры ДНК и разработка новых молекулярных методов ее анализа, идентификация специфических геномных изменений, ответственных за неопластическую трансформацию, стали поворотными моментами в разработке инновационных лекарственных средств — таргетных противоопухолевых агентов, направленных на молекулярные и генетические мишени опухолевого роста. Переход от эмпирического скрининга агентов, механизм действия которых основан на ингибировании пролиферации опухолевых клеток, к молекулярно-нацеленным методам анализа привел к возникновению ряда важных методологических вопросов, связанных с доклинической разработкой инновационных лекарственных средств. Цель работы — анализ общих принципов и особенностей доклинических исследований эффективности и безопасности современных противоопухолевых препаратов различных классов для усовершенствования существующих национальных методических рекомендаций. В работе рассмотрены вопросы доклинических исследований различных классов противоопухолевых лекарственных средств (синтетических химиотерапевтических препаратов, гормонов и антагонистов гормонов, препаратов алкилирующего действия, антиметаболитов, препаратов микробного и растительного происхождения, а также моноклональных антител). Приведены общие принципы изучения их фармакологической активности в системах in vitro, ex vivo и in vivo, определения фармакокинетических параметров, описаны используемые методы и модели исследований. Указаны особенности определения генотоксичности, канцерогенности, репродуктивной токсичности, мутагенности, острой и хронической токсичности препаратов разных групп, перечислены критерии выбора доз для токсикокинетических исследований. Необходимость гармонизации национальных требований к проведению доклинических исследований с европейскими нормами влечет за собой унификацию терминологии и дальнейшую разработку общих алгоритмов выбора доз и определения необходимых объемов исследования. Использование биомаркеров в доклинических исследованиях позволит исключить дальнейшие исследования неэффективных соединений