Orchestrating the measurements on twelve magnet test benches

The final LHC dipole series test set-up will consist of 12 benches, organised in 6 clusters of two benches sharing the largest and most expensive devices. This sharing is made possible by a deliberate de-phasing of the tests among magnets, ensuring an optimum use of resources, such as cryogenics and power equipment, without limiting the total throughput. To orchestrate the measurements a Test Master is needed to organise the tests per cluster and a Resource Manager to centralise the booking of the resources

Alteration of some biological properties of Lactobacillus under the action of RNAse

The influence of RNAse from Bacillus intermedius on the growth of the industrial strain Lactobacillus plantarum 8R-A3 was studied. It was shown that the stimulating effect of the enzyme depended on its dose and manifested itself in decreasing the growth lag phase. At the same time the growth stimulating dose of RNAse increased the Lactobacillus adhesion to the epithelial cells and promoted secretion of proteinases from Lactobacillus to the culture medium. The possible use of RNAse as a stimulant of the growth of industrial strains was demonstrated which is advantageous for colonization of the biological surfaces

Planning of clinical trial programmes for medicines for the treatment of obesity

Scientific relevance. Obesity is a significant public health problem. Currently, the Russian Federation and the other Member States of the Eurasian Economic Union (EAEU) do not have regulatory documents and recommendations for planning clinical trials (CTs) of new (original) medicines for the treatment of obesity.Aim. The study aimed to provide recommendations on the basic principles of planning and conducting CTs of medicines for the treatment of obesity.Discussion. The authors reviewed the requirements for conducting CTs of medicines for the treatment of obesity set forth by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). In addition, the authors analysed approaches to CTs providing for a reliable evaluation of the efficacy and safety of medicines for the treatment of obesity. The primary endpoint of such CTs is a statistically significant loss of at least 5% of the baseline weight after 12 months of treatment. Secondary endpoints include assessments of abdominal obesity reduction, subcutaneous and visceral fat reduction, and the medicinal product’s effect on maintaining a reduced body weight.Conclusions. In addition, CTs should investigate the effects of treatment on cardiovascular risk factors and cardiovascular morbidity/mortality. A CT protocol should define the intercurrent events that should be considered in the analysis of trial results. When investigating the safety of medicines for the treatment of obesity, studies should focus on neuropsychiatric safety, the potential for abuse/addiction and withdrawal reactions, and the development of valvulopathy and pulmonary hypertension. These recommendations may be of use to experts evaluating clinical development programmes or marketing authorisation submissions for medicines for the treatment of obesity

Current Approaches to Demonstration of Therapeutic Equivalence of Locally-Acting Gastrointestinal Drugs

Evolution of knowledge about pharmacokinetics and pharmacodynamics of locally acting products, and an increase in the number of generics and medicines under development have laid the ground for the development of new scientific approaches to planning and conducting of therapeutic equivalence studies of medicinal products acting locally in the gastrointestinal (GI) tract. To date, many international guidelines on planning and conducting of bioequivalence (BE) studies of locally acting GI products have been updated, however, there are still no such guidelines in the Russian Federation and the Eurasian Economic Union (EAEU). Therefore, elaboration of common methodological approaches to the planning of clinical studies of these products is of particular relevance for the EAEU. The aim of the study was to analyse foreign approaches to planning, conducting, and evaluation of therapeutic equivalence studies of locally acting GI products. The paper analyses the guidelines of the European Medicines Agency and the US Food and Drug Administration on the planning, conduct, and evaluation of BE studies of locally acting GI products. The analysis demonstrated that BE clinical trials are giving way to in vitro studies providing a sensitive and accurate assessment of the differences between a locally acting GI product and the reference product, based on careful consideration of the medicine’s mechanism of action, dosage form, and site of action. The paper gives examples of test methods applied to medicinal products with a complex biopharmaceutical profile whose bioequivalence assessment is challenging, with a special focus on mesalazine products. The results of the analysis may be used for elaboration of a harmonised methodological approach to planning and conducting therapeutic equivalence studies of locally acting GI products in the Russian Federation and EAEU

Treatment for mixed cognitive impairments and emotional disorders in young and middle-aged patients

Objective: to evaluate the efficacy of Tanakan® (EGB761®) used in young and middle-aged patients with mixed cognitive impairments (CI) and emotional diseases.Patients and methods. An open-label observational study of the efficacy of Tanakan® was conducted in 54 patients aged 18–4 years with CI and psychoemotional disorders. Tanakan® was administered at a daily dose of 120 mg (40 mg t.i.d) for 3 months.Results. Tanakan® therapy resulted in health improvement, as shown by the HAM (Health, Activity, Mood) questionnaire; the mean score of the latter increased from 3.86 at baseline to 4.84 after 3 months of treatment. There were improvements in three HAM questionnaire items: the mean score of the item «Health» increased from 3.69 to 4.79; that of the item «Activity» from 3.65 to 4.58, and that the item «Mood» from 4.25 to 5.14 after the completion of the investigation.Tanakan® therapy also demonstrated improvements in memory (the mean number of correctly repeated words increased from 5.7 to 6.7 at the beginning of a visit and from 4.2 to 5.8 at its end) and in attention (the mean symbol-digit coding test score increased from 48.1 to 55.7%. There were no clinically relevant differences between patients with higher and secondary education in the efficacy of Tanakan®.Conclusion. Tanakan® had a very good safety profile; no adverse drug events were recorded during the investigation. Almost all the 53 (98.1%) of the 54 patients were satisfied with Tanakan® therapy results after 3 months of treatment

Планирование программы клинических исследований препаратов для лечения ожирения

Obesity is a significant public health problem. Currently, the Russian Federation and the other Member States of the Eurasian Economic Union (EAEU) do not have regulatory documents and recommendations for planning clinical trials (CTs) of new (original) medicines for the treatment of obesity.The aim of the study was to provide recommendations on the basic principles of planning and conducting CTs of medicines for the treatment of obesity.The authors reviewed the requirements for conducting CTs of medicines for the treatment of obesity set forth by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). In addition, the authors analysed approaches to CTs providing for a reliable evaluation of the efficacy and safety of medicines for the treatment of obesity. The primary endpoint of such CTs is a statistically significant loss of at least 5% of the baseline weight after 12 months of treatment. Secondary endpoints include assessments of abdominal obesity reduction, subcutaneous and visceral fat reduction, and the medicinal product’s effect on maintaining a reduced body weight. In addition, CTs should investigate the effects of treatment on cardiovascular risk factors and cardiovascular morbidity/mortality. A CT protocol should define the inter-current events that should be considered in the analysis of trial results. When investigating the safety of medicines for the treatment of obesity, studies should focus on neuropsychiatric safety, the potential for abuse/addiction and withdrawal reactions, and the development of valvulopathy and pulmonary hypertension. These recommendations may be of use to experts evaluating clinical development programmes or marketing authorisation submissions for medicines for the treatment of obesity.Нормативные документы и рекомендации по планированию клинических исследований (КИ) новых препаратов для лечения ожирения в Российской Федерации и в других государствах — членах Евразийского экономического союза в настоящее время отсутствуют.Цель работы: представить рекомендации по основным принципам планирования и проведения КИ препаратов для лечения ожирения.Проведен анализ требований к проведению КИ препаратов для лечения ожирения Европейского агентства по лекарственным средствам, Управления по контролю за качеством продуктов питания и лекарственных средств. Рассмотрены подходы, позволяющие достоверно оценить эффективность и безопасность препаратов для лечения ожирения при проведении КИ. Показано, что первичной конечной точкой является демонстрация статистически значимого снижения массы тела по крайней мере на 5% от исходной массы тела после 12 мес. терапии. Вторичные конечные точки: уменьшение степени выраженности абдоминального ожирения; оценка количества подкожного и висцерального жира; оценка влияния препарата на поддержание сниженной массы тела. Должно быть оценено влияние препарата на сердечно-сосудистые факторы риска и сердечно-сосудистую заболеваемость/смертность. В протоколе КИ необходимо представить определение интеркуррентных событий, влияние которых также нужно учитывать при анализе полученных результатов. В отношении безопасности препаратов для лечения ожирения следует сделать акцент на нейропсихической безопасности, потенциале злоупотреблений/зависимости и реакциях отмены, развитии вальвулопатии и легочной гипертензии. Настоящие рекомендации могут использоваться экспертами, осуществляющими оценку программы клинической разработки препаратов для лечения ожирения и экспертизу с целью регистрации

ИССЛЕДОВАНИЕ АНТИБИОТИКО- И ФАГОЧУВСТВИТЕЛЬНОСТИ НОЗОКОМИАЛЬНЫХ ШТАММОВ МИКРОБОВ, ВЫДЕЛЕННЫХ ОТ ПАЦИЕНТОВ ТРАНСПЛАНТОЛОГИЧЕСКОЙ КЛИНИКИ

Antibiotic and fagosensitivity most etiologically important nosocomial strains of bacteria – Pseudomonas aeru- ginosa, Klebsiella pneumoniae, E. coli, Proteus spp., Staphylococcus spp. were studied. Multiple drug-resistant bacteria as gram-positive and gram-negative, isolated from 8 substrates, had been demonstrated. With regard to the sensitivity of Pseudomonas aeruginosa >40% was observed in 40–50% of the strains to aminoglycosides – aztreonam, amikacin, netilmicin, and only 23–25% of the strains – to gentamicin and levofloxacin (an average of antibiotic susceptibility was 27%). All strains of ESBL Klebsiella drew up and were sensitive only to imipenem, meropenem and aminoglycosides. Specific phages lysed 43–48% of the strains Pseudomonas aeruginosa and Klebsiella pneumoniae, E. coli, Pro- teus spp., multidrug resistant strains of Staphylococcus spp. It is proposed to introduce the use of phages in clinical practice. Исследована антибиотико- и фагочувствительность наиболее этиологически важных нозокомиальных штаммов микробов – синегнойных палочек, клебсиелл, кишечных палочек, протеев, стафилококков. Установлена множественная резистентность штаммов бактерий как грамположительных, так и грамотрицательных, изолированных из 8 субстратов. В отношении синегнойной палочки чувствительность >40% отмечена у 40–50% штаммов к аминогликозидам – азтреонаму, амикацину, нетилмицину и только у 23–25% штаммов – к гентамицину и левофлоксацину (в среднем антибиотикочувствительность составила 27%). Все штаммы клебсиелл вырабатывали БЛРС и были чувствительны только к имипенему, меропенему и аминогликозидам. Специфические бактериофаги лизировали 43–48% штаммов синегнойных палочек и клебсиелл, кишечные палочки, протеи, множественно резистентные штаммы стафилококков. Предлагается внедрять использование бактериофагов в клиническую практику трансплантологических клиник.

Prevalence of occult hepatitis B infection among blood donors in Saint Petersburg

The aim of this study was to assess the prevalence of occult hepatitis B infection among blood donors in St. Petersburg, as well as to characterize the identified virus isolates. The study material was represented by 2800 blood plasma samples collected in 2019 from blood donors living in St. Petersburg. The ELISA study for HBV marker rate consisted of HBsAg, anti-HBs IgG, anti-HBcore IgG. HBV DNA was analyzed by nested PCR with real-time hybridization-fluorescence detection on three targets allowing to determine virus DNA at low viral load, including HBsAg-negative chronic hepatitis B. Hepatitis B serological markers were detected in 69.43% of those surveyed, HBsAg was found in 0.43% of individuals, and all of which donated blood first time. A significant excess of the anti-HBcore IgG antibodies occurrence among primary donors (15.1%) compared with repeated/regular donors (7.48%) was shown. The prevalence of virus DNA in the group was 3.14%, including 2.71% of cases in HBsAg-negative CHB. Based on phylogenetic analysis of 88 isolates, HBV subgenotypes were determined in the following order: D1 and D2, 40.91% each, D3 and A2, 9.09% each. While determining the serological subtype in detected isolates, the serotype ayw3 (52.27%) vs ayw2 (46.59%) and adw2 (10.23%) prevailed. Drug resistance mutations, including compensatory ones, were detected in six examined patients (6.82%). In all genotype D isolates, multiple amino acid substitutions were identified in the RT, SHB, MHB, LHB, and Core regions; mutations in the preCore region were detected in 21.59% samples. In the MHR of the HBV genotype D genome, twenty-six positions were identified in which amino acid substitutions occurred, and all isolates showed modifications at positions 113, 114, 131, 134, 159, 161, 168, in 76 — at position 122, in 68 — at position 127, in 36 — at position 118, in 24 — at position 128. In HBV A2 isolates, mutations T113S, S143T, Y161F were identified. Nine isolates in the preCore region showed a polymorphism including a stop codon W28*W; in five isolates the W28S substitution was shown in the same position, and the W28*S variant was found in one more sample. The high incidence of HBsAg-negative CHB cases among blood donors, as well as the predominance of HBV isolates that simultaneously carry mutations resulting in diagnostic failure of HBsAg tests and prophylactic failure of immunoglobulin or vaccines and virus reactivation, mutations that contribute to disease progression obviously pose a threat to health and require to be further examined

Alteration of some biological properties of Lactobacillus under the action of RNAse

The influence of RNAse from Bacillus intermedius on the growth of the industrial strain Lactobacillus plantarum 8R-A3 was studied. It was shown that the stimulating effect of the enzyme depended on its dose and manifested itself in decreasing the growth lag phase. At the same time the growth stimulating dose of RNAse increased the Lactobacillus adhesion to the epithelial cells and promoted secretion of proteinases from Lactobacillus to the culture medium. The possible use of RNAse as a stimulant of the growth of industrial strains was demonstrated which is advantageous for colonization of the biological surfaces