The Anticancer Peptide TAT-RasGAP317-326 Exerts Broad Antimicrobial Activity.

Antibiotic resistance has become a major health issue. Nosocomial infections and the prevalence of resistant pathogenic bacterial strains are rising steadily. Therefore, there is an urgent need to develop new classes of antibiotics effective on multi-resistant nosocomial pathogenic bacteria. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, induces cancer cell death, inhibits metastatic progression, and sensitizes tumor cells to various anti-cancer treatments in vitro and in vivo. We here report that TAT-RasGAP317-326 also possesses antimicrobial activity. In vitro, TAT-RasGAP317-326, but not mutated or truncated forms of the peptide, efficiently killed a series of bacteria including Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa. In vivo experiments revealed that TAT-RasGAP317-326 protects mice from lethal E. coli-induced peritonitis if administrated locally at the onset of infection. However, the protective effect was lost when treatment was delayed, likely due to rapid clearance and inadequate biodistribution of the peptide. Peptide modifications might overcome these shortcomings to increase the in vivo efficacy of the compound in the context of the currently limited antimicrobial options

Оптимизация параметров тепловой обработки при сканирующем перемещении точечного источника тепла

Трофименко Е. Г. Оптимизация параметров тепловой обработки при сканирующем перемещении точечного источника тепла / Е. Г. Трофименко, Е. В. Шалабин, В. В. Дубовой // Труды Одесского политехнического университета. – 1998. – Вып. 2(6). – С. 186 – 187.Задача теплової обробки розвиненої поверхні за допомогою точкового джерела тепла подана як оптимізаційна. Наведено цільову функцію оптимізації та алгоритм розв'язання такої задачі.Задача тепловой обработки развитой поверхности с помощью точечного источника тепла подана как оптимизационная . Приведены целевая функция оптимизации и алгоритм решения такой задачи.The problem of developed surface thermal processing by the mean of pointwised heat source is considered herewith as this one of optimisation. A target oriented function of optimisation and problem solution algorithm are given

Antiatherogenic Potential of Transcranial Electrical Stimulation in a High-Fructose/High-Fat Diet: Experimental Randomized Trial

Background. Transcranial electrical stimulation is a promising method for correction of malnutrition-induced hyperlipidemia, in the absence of indications for drug hypolipidemic therapy in young and middle-aged patients with low and moderate cardiovascular risk. Objectives — to study the effect of transcranial electrical stimulation on lipid metabolism in a high-fructose/high-fat (HFHF) diet in rats.Methods. An experimental randomized trial was performed to study the effect of transcranial electrical stimulation on lipid metabolism in a high-calorie diet enriched with fructose and saturated animal fat in rats. The experiments involved 180 outbred male rats and were carried out on the basis of the vivarium of Kuban State Medical University. The animals were divided into three groups: group 1 (control group, n = 60) — followed a standard diet; group 2 (comparison group, n = 60) — followed a HFHF diet; group 3 (experimental group, n = 60) — underwent transcranial electrical stimulation against the background of a HFHF diet. According to the target reference point of the study, the groups were divided into three equal subgroups of 20 rats each: subgroup A — day 30, subgroup B — day 60, and subgroup C — day 90 (biomaterial sampling and euthanasia were carried out on those days). In the obtained blood samples, the following lipid metabolism parameters were evaluated: total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and atherogenic index. Statistical analysis was performed using Microsoft Office Excel 2021 (Microsoft, USA), GraphPadPrism 9 (GraphPad Software, USA) and Statistica 13.3 (StatSoft, USA).Results. On the 30th day of the study, it was noted that in group 3, the concentration of low-density lipoprotein cholesterol was 14.9% lower and the atherogenic index was 30.8% lower (p < 0.05) than in group 2, while total cholesterol concentration, triglycerides, and high-density lipoprotein cholesterol had no statistically significant differences (p > 0.05). On the 60th day of the study, in group 3, when compared to group 2, the concentration of total cholesterol was 18.7% lower, low-density lipoprotein cholesterol was 42.9% lower, high-density lipoprotein cholesterol was 16.7% higher, and the atherogenic index was 56.3% lower (p < 0.05), while triglycerides had no statistically significant differences (p > 0.05). On the 90th day of the study, in group 3, when compared to group 2, the concentration of total cholesterol was 29.2% lower, the concentration of triglycerides was 36.0% lower, low-density lipoprotein cholesterol was 42.8% lower, and the atherogenic index was 57.0% lower (p < 0.05), while the concentration of high-density lipoprotein cholesterol had no statistically significant differences (p > 0.05).Conclusion. High-fructose/high-fat diet leads to a progressive increase in the serum concentration of low-density lipoprotein cholesterol, total cholesterol, triglycerides, as well as to a moderate decrease in high-density lipoprotein cholesterol and a growth in the atherogenic index. Transcranial electrical stimulation has a moderate lipid-lowering effect, manifested in the form of a decrease in the serum concentration of low-density lipoprotein cholesterol, total cholesterol and atherogenic index, while the effect on the concentration of triglycerides and high-density lipoprotein cholesterol is insignificant

Моделирование оптимальных геометрических параметров пьезоэлементов для полизмерительных мономорфных датчиков

Салагор А. М. Моделирование оптимальных геометрических параметров пьезоэлементов для полизмерительных мономорфных датчиков / А. М. Салагор, Е. Г. Трофименко, Л. Н. Буката // Вісник Інженерної академії України. - К.: ІАУ, 2015. - № 1. - С. 151-157.В работе исследованы зависимости основных характеристик пьезокерамики от соотношений геометрических параметров пьезоэлементов в форме бруска. Исследована схемотехническая модель мономорфного пьезокерамического преобразователя для измерения двух физических величин, проведены экспериментальные исследования. В результате анализа было установлено оптимальное соотношение геометрических параметров пьезоэлемента в виде бруска.В роботі досліджено залежності основних характеристик п'єзокераміки від співвідношень геометричних параметрів п'єзоелементів у формі бруска. Досліджено схемотехнічна модель мономорфного п'єзокерамічного перетворювача для вимірювання двох фізичних величин, проведені експериментальні дослідження. В результаті аналізу було встановлено оптимальне співвідношення геометричних параметрів п'єзоелемента у вигляді бруска

Repeat Detector: versatile sizing of expanded tandem repeats and identification of interrupted alleles from targeted DNA sequencing

Targeted DNA sequencing approaches will improve how the size of short tandem repeats is measured for diagnostic tests and preclinical studies. The expansion of these sequences causes dozens of disorders, with longer tracts generally leading to a more severe disease. Interrupted alleles are sometimes present within repeats and can alter disease manifestation. Determining repeat size mosaicism and identifying interruptions in targeted sequencing datasets remains a major challenge. This is in part because standard alignment tools are ill-suited for repetitive and unstable sequences. To address this, we have developed Repeat Detector (RD), a deterministic profile weighting algorithm for counting repeats in targeted sequencing data. We tested RD using blood-derived DNA samples from Huntington’s disease and Fuchs endothelial corneal dystrophy patients sequenced using either Illumina MiSeq or Pacific Biosciences single-molecule, real-time sequencing platforms. RD was highly accurate in determining repeat sizes of 609 blood-derived samples from Huntington’s disease individuals and did not require prior knowledge of the flanking sequences. Furthermore, RD can be used to identify alleles with interruptions and provide a measure of repeat instability within an individual. RD is therefore highly versatile and may find applications in the diagnosis of expanded repeat disorders and in the development of novel therapies

Insertion and Substitution Chemistry at the Boron Fourth Position in Charge-Neutral Zwitterionic Tripodal Tris(methimazolyl)borate Ligands

A number of new charge-neutral zwitterionic tris(methimazolyl)borate ligands have been synthesized, either by substitution of the dimethylamine group in the adduct (dimethylamine)tris(methimazolyl)borane (1) or by insertion into its B–N(dimethylamine) bond by an unsaturated Lewis base. Two new anionic ligands, (thiocyanato)tris(methimazolyl)borate and (cyano)tris(methimazolyl)borate, have also been accessed by this method

Ингаляционные глюкокортикостероиды в лечении хронической обструктивной болезни легких

The main objectives of chronic obstructive pulmonary disease (COPD) therapy are to reduce the severity of symptoms and the risk of exacerbations. The article discusses the role of local and systemic inflammation in the pathogenesis of COPD as well as various mechanisms of pharmacological influence on it. Approaches to prescribing basic therapy for patients with COPD, recommended by various national and global guidelines (clinical recommendations of the Russian respiratory society, criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), guidelines of the National Institute for Health and Clinical Excellence (NICE)), as well as recommendations on the therapy frequency review are considered. Currently, so-called triple combinations – fixed combinations of double bronchodilators with inhaled glucocorticosteroids – are being developed and registered in the world, and their place and significance in the treatment of COPD raise many discussions. The paper discusses the role of fixed triple combinations in reducing the incidence of COPD exacerbations, the impact on functional and patient-reported outcomes, and provides recommendations for the use of triple combinations in patients with COPD, taking into account the benefit/risk ratio.Основными задачами терапии хронической обструктивной болезни легких (ХОБЛ) являются уменьшение выраженности симптомов заболевания и снижение риска обострений. В статье обсуждается роль локального и системного воспаления в патогенезе ХОБЛ, а также различные механизмы фармакологического влияния на него. Рассмотрены подходы к назначению базисной терапии пациентам с ХОБЛ, рекомендуемые различными национальными и глобальными руководствами (клинические рекомендации Российского респираторного общества, критерии Глобальной стратегии по лечению хронической обструктивной болезни легких (Global Initiative for Chronic Obstructive Lung Disease – GOLD), руководство Национального института совершенствования здравоохранения Великобритании (National Institute for Health and Clinical Excellence – NICE)), а также рекомендации по периодичности пересмотра терапии. В настоящее время в мире разрабатываются и регистрируются т. н. тройные комбинации – фиксированные комбинации двойных бронхолитических препаратов с ингаляционными глюкокортикостероидами, при этом их место и значение в лечении ХОБЛ вызывает многочисленные дискуссии. В работе обсуждается роль фиксированных тройных комбинаций при снижении частоты обострений ХОБЛ, воздействии на функциональные и пациент-репортированные исходы, приведены рекомендации по применению тройных комбинаций у пациентов с ХОБЛ с учетом соотношения польза / риск

Algorithm for cancelling inhaled corticosteroids in patients with chronic obstructive pulmonary disease. Regional Meeting of Experts

A treatment algorithm for chronic obstructive pulmonary disease (COPD) implies that all patients with COPD should receive long-acting anticholinergic bronchodilators, long-acting β2 -agonists, or a combination of these drugs as the basic therapy. Inhaled corticosteroids (IHCs) are indicated for a limited group of patients with COPD and have a number of contraindications. Clear indications for the IHCs use as dual therapy in combination with long-acting β2 -agonists, or as triple therapy in addition to long-acting anticholinergic bronchodilators combination, were determined. IHCs in combination with long-acting bronchodilators are prescribed for patients with COPD in cases of non- infectious exacerbations recurring during the year in frames of treatment with long-acting bronchodilators with anamnestic indications or the presence of bronchial asthma and/or the eosinophil number in the blood test without exacerbation >300 cells/μl. Algorithm for IHC cancellation has been developed for patients with COPD due to several causes: complications development as a result of IHC prolonged treatment; evidence of the benefits or equivalent effects of long-acting bronchodilators compared to inhaled corticosteroid-containing therapy.Алгоритм лечения хронической обструктивной болезни легких (ХОБЛ) подразумевает, что все пациенты с ХОБЛ должны получать длительнодействующие антихолинергические бронходилататоры (ДДАХ), длительнодействующие β2 -агонисты (ДДБА) либо сочетания этих препаратов в качестве базисной терапии. Ингаляционные глюкокортикостероиды (ИГКС) показаны ограниченной группе пациентов с ХОБЛ и имеют ряд противопоказаний. Определены четкие показания к применению ИГКС в качестве двойной терапии в сочетании с ДДБА либо тройной терапии дополнительно в сочетании с ДДАХ. ИГКС в сочетании с ДДБД назначаются больным с ХОБЛ в случаях повторяющихся в течение года неинфекционных обострениях на фоне лечения ДДБД при анамнестических указаниях или наличии бронхиальной астмы и/или количестве эозинофилов крови вне обострения >300 кл./мкл. Разработан алгоритм отмены ИГКС у пациентов с ХОБЛ в связи с развитием осложнений в результате длительной терапии ИГКС и наличием доказательств преимущества или равнозначного эффекта ДДБД в сравнении с ИГКС-терапией

Возможности диагностики и лечения больных ХОБЛ в рамках реальной клинической практики. Подходы к терапии пациентов с различными фенотипами по GOLD (2019): материалы Совета экспертов Сибирского федерального округа, Читы и Бурятии от 15.03.19

Chronic obstructive pulmonary disease (COPD) is a global problem in modern medicine. In recent years, the medical community’s understanding of COPD has changed significantly, which is primarily due to the emergence of a new classification and the identification of various phenotypes of the disease. These changes could not affect the tactics of COPD treatment. The article discusses not only the debatable issues of treating COPD; it provides an overview of changes in international (Global Initiative for Chronic Obstructive Lung Disease, 2018) and national (2019) recommendations, but also the significance and benefits of triple therapy in terms of evidence-based medicine as well as the benefits of extra-fine drugs in the treatment of bronchial obstructive syndrome.Хроническая обструктивная болезнь легких (ХОБЛ) представляет собой глобальную проблему современной медицины. За последние годы представление медицинского сообщества о ХОБЛ существенно изменилось, что связано в первую очередь с появлением новой классификации и выделением различных фенотипов заболевания. Эти изменения не могли не повлиять на тактику лечения ХОБЛ. В статье рассматриваются не только дискуссионные вопросы лечения ХОБЛ, представлен обзор изменений в международных (Гло - бальная инициатива по диагностике, лечению и профилактике ХОБЛ (Global Initiative for Chronic Obstructive Lung Disease, 2018)) и национальных (2019) рекомендациях, но и значение и преимущества тройной терапии с точки зрения доказательной медицины, а также преимущества экстрамелкодисперсных препаратов при лечении бронхообструктивного синдрома

Combined Experimental and Computational Studies on the Nature of Aromatic C−H Activation by Octahedral Ruthenium(II) Complexes: Evidence for σ-Bond Metathesis from Hammett Studies

Octahedral ruthenium complexes of the type TpRu(L)(NCMe)R [Tp = hydridotris(pyrazolyl)borate; R = alkyl or aryl; L = CO or PMe3] have been shown previously to initiate the C-H activation of aromatic substrates. In order to probe the nature of the C-H activation step, reaction rates have been theoretically obtained for the conversion of TpRu(L)(η2-C, C-C6H5X)Me to TpRu(L)(P-C6H4X) and CH4 where X is varied among Br, Cl, CN, F, H, NH2, NO 2, and OMe. A linear Hammett correlation is calculated with a positive p value of 2.6 for L = CO and 3.2 for L = PMe3. Calculated kinetic data for the aromatic C-H activations indicate that an electrophilic aromatic substitution mechanism is unlikely. While experiments cannot fully replicate the entire range of calculated Hammett plots, reactivity trends are consistent with the calculations that suggest activation barriers to overall metal-mediated arene C-H bond cleavage are reduced by the presence of electron-withdrawing groups in the position para to the site of activation. Previous mechanistic studies, as well as the structure and imaginary vibrational modes of the present transition states, validate that the C-H activation for this family of TpRu complexes occurs through a σ-bond metathesis-type pathway. © 2007 American Chemical Society