Effect of a sorbent composition based on aluminum oxide and polydimethylsiloxane on the reproductive system of <i>db/db</i> female mice with genetically determined obesity and type 2 diabetes mellitus

Metabolic syndrome, obesity, type 2 diabetes mellitus are characterized by the accumulation of toxic metabolic products in the internal environment of the organism. The development of innovative medicines based on a sorbent matrix modified with  biologically active molecules remains relevant. The sorbent composition from aluminum oxide and polydimethylsiloxane is considered promising. The aim of the study. To investigate the effect of the sorbent composition from aluminum oxide and polydimethylsiloxane on the uterus and ovaries of db/db  mice with obesity and type 2 diabetes mellitus. Materials and methods. The sorbent composition (0.665 g/kg in 200 μl of distilled water) was administered to 14-week-old animals through an intragastric tube once a day for 7 days. The comparison groups were female rats injected with placebo (daily intragastrical administration of 200 µl of water for 7 days) and intact animals. Digital images of light-optical preparations stained with hematoxylin and eosin were processed using Image-Pro Plus 4.1 software. In the ovaries, the numerical density of primordial, primary, secondary follicles and corpus luteum was determined. The width of the uterus layers, the diameters of the blood and lymphatic vessels, the width of the interstitial fissures in both organs were measured. The statistical significance of differences was determined using the Mann – Whitney test. Results. In the myometrium and endometrium of the uterus of db/db mice, dilatation of arteries, veins, lymphatic vessels and edema were noted due to the accumulation of tissue fluid in the interstitium layers. There were no tertiary follicles in the ovaries. The introduction of the sorbent composition contributed to a decrease in the diameters of arteries, veins, lymphatic vessels of the uterus, a decrease in edema in both organs due to the narrowing of the prelymphatic slits, and stimulated an increase in the numerical density of secondary follicles. Conclusion. A corrective effect of the sorbent composition of aluminum oxide and  polydimethylsiloxane on prelymphatic slits, blood and lymphatic vessels in the uterus and ovaries in db/db mice with obesity and type 2 diabetes mellitus was revealed

The isolated proteolytic domain of Escherichia coli ATP-dependent protease Lon exhibits the peptidase activity

AbstractSelective protein degradation is an energy-dependent process performed by high-molecular-weight proteases. The activity of proteolytic components of these enzymes is coupled to the ATPase activity of their regulatory subunits or domains. Here, we obtained the proteolytic domain of Escherichia coli protease Lon by cloning the corresponding fragment of the lon gene in pGEX-KG, expression of the hybrid protein, and isolation of the proteolytic domain after hydrolysis of the hybrid protein with thrombin. The isolated proteolytic domain exhibited almost no activity toward protein substrates (casein) but hydrolyzed peptide substrates (melittin), thereby confirming the importance of the ATPase component for protein hydrolysis. Protease Lon and its proteolytic domain differed in the efficiency and specificity of melittin hydrolysis

RESEARCH OF EFFECTIVE WAYS TO REDUCE THERMAL LOSSES IN HIGH-TEMPERATURE PROCESSES AND INSTALLATIONS

В работе проанализированы эффективные способы снижения тепловых потерь через стенку в высокотемпературных процессах и установках. Построены графики зависимости расхода топлива от потери количества теплоты через кладку, график зависимости плотности количества теплоты от температуры стенки.The paper analyzes effective ways to reduce heat loss through the wall in hightemperature processes and installations. Graphs of the dependence of fuel consumption on the loss of the amount of heat through the masonry, and a graph of the dependence of the density of the amount of heat on the wall temperature are constructed

Вопросы безопасности и оптимального дозирования ингибитора интерлейкина 17А (секукинумаб) при лечении псориатического артрита у пациента с сопутствующим вирусным гепатитом С

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the group of spondylitides, which is associated with psoriasis. The decisive role is played by the activation of the interleukin (IL)-23/IL-17 axis in the pathogenesis of PsA [1]. Secukinumab (SEC) is a fully human antibody that binds to human IL-17A and neutralizes the activity of this cytokine. That the patient has concomitant diseases, chronic hepatitis B virus infection and hepatitis C viral (HCV) infection in particular, limits the use of tumor necrosis factor- α inhibitors in the treatment of PsA [2, 3]. The paper describes a clinical case that demonstrates the successful treatment with SEC in a patient with PsA and concomitant HCV infection. In addition to the safety aspects of the use of SEC to treat chronic HCV infection, the issues on optimal dosing of the drug are discussed.Псориатический артрит (ПсА) – хроническое воспалительное заболевание из группы спондилоартритов, ассоциированное с псориазом. Решающая роль в патогенезе ПсА отводится активации оси интерлейкин (ИЛ) 23/ИЛ17 [1]. Секукинумаб (СЕК) представляет собой полностью человеческие антитела, которые связываются с ИЛ17А человека и нейтрализуют активность этого цитокина. Наличие у пациента сопутствующих заболеваний, в частности хронического вирусного гепатита В и вирусного гепатита С (ВГС), ограничивает применение ингибиторов фактора некроза опухоли α в лечении ПсА [2, 3].Приведено клиническое наблюдение, демонстрирующее успешное лечение СЕК у пациента с ПсА и сопутствующим ВГС. Помимо аспектов безопасности применения СЕК при хроническом ВГС, обсуждаются вопросы оптимального дозирования препарата

РЕГУЛИРОВАНИЕ ОТНОШЕНИЙ МЕЖДУ ЗАКАЗЧИКОМ И ИСПОЛНИТЕЛЕМ ГОСУДАРСТВЕННОГО ОБОРОННОГО ЗАКАЗА

Below is the original author's method of assessment of financial and economic sustainability of enterprises-performers of the state defense order. This method takes into account the financial and economic performance of the enterprise. The proposed comprehensive indicator of financial and economic sustainability can be used by the state customer at the stage of analyzing the possibility of the state contract execution by potential contractors.Предложен оригинальный авторский метод оценки финансово-экономической устойчивости предприятий – исполнителей государственного оборонного заказа. Метод учитывает финансовые и экономические показатели деятельности предприятия. Предлагаемый комплексный показатель оценки финансово-экономической устойчивости может быть использован государственным заказчиком на этапе анализа возможностей выполнения государственного контракта потенциальными исполнителями

Клинические особенности анкилозирующего спондилита у пациентов с вторичным АА-амилоидозом

Renal AA amyloidosis is the most severe type of renal pathology in patients with ankylosing spondylitis (AS). The characteristic symptoms of AA amyloidosis in rheumatic diseases do not often occur for years, making it difficult to diagnose it early and to start adequate therapy.Objective: to identify the clinical features of AS complicated by secondary AA amyloidosis.Patients and methods. The investigation enrolled 9 patients with AS (according to the 1984 modified New York criteria) and histologically confirmed secondary AA amyloidosis (Group 1). A comparison group included 216 AS patients without amyloidosis (Group 2).Results and discussion. In Group 1 patients, the age at the onset of AS was significantly less and the disease duration was 4 times longer than those in Group 2. All the patients with AA amyloidosis had enthesitis and arthritis, including those of the hip joints. The scores of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), and the acute phase inflammation index CRP were higher in Group 1 than in Group 2.Conclusion. The clinical feature of AS complicated by secondary AA-amyloidosis is the long duration of the disease and the high frequency of juvenile onset, non-axial manifestations (arthritis, coxitis and enteritis), as well as the high activity of systemic inflammation.Почечный АА-амилоидоз – самый тяжелый тип патологии почек у пациентов с анкилозирующим спондилитом (АС). Нередко характерные симптомы АА-амилоидоза при ревматических заболеваниях не проявляются годами, затрудняя его раннюю диагностику и начало адекватной терапии.Цель исследования – выявление особенностей клинической картины АС, осложненного вторичным АА-амилоидозом.Пациенты и методы. В исследование включено 9 больных АС (согласно модифицированным Нью-Йоркским критериям, 1984) с гистологически подтвержденным вторичным АА-амилоидозом (1-я группа). Во 2-ю группу (группа сравнения) вошли 216 пациентов с АС без амилоидоза.Результаты и обсуждение. У пациентов 1-й группы возраст дебюта АС был значительно меньше, а длительность болезни – в 4 раза больше, чем у больных 2-й группы. Все больные с АА-амилоидозом имели энтезит и артрит, в том числе тазобедренных суставов. Индексы BASDAI и ASDAS-СРБ, а также острофазовый показатель воспаления – СРБ – у пациентов с АА-амилоидозом были выше, чем в группе сравнения.Заключение. Особенностью клинической картины АС, осложненного вторичным АА-амилоидозом, являются большая длительность заболевания и высокая частота ювенильного начала, внеаксиальных проявлений (артрит, коксит и энтезит), а также высокая активность системного воспаления

Опыт эффективного использования ингибиторов интерлейкина 6 у больных анкилозирующим спондилитом со вторичным амилоидозом

Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p&lt;0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p&lt;0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p&lt;0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p&lt;0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.В рандомизированных клинических исследованиях, в которых изучалась эффективность ингибиторов интерлейкина 6 (иИЛ6) тоцилизумаба (ТЦЗ) и сарилимумаба при анкилозирующем спондилите (АС), показана их неэффективность. Однако имеются многочисленные данные о том, что ИЛ6 активно участвует в патогенезе данного заболевания. Кроме того, установлена эффективность иИЛ6 у пациентов со вторичным АА-амилоидозом.Цель исследования – проанализировать результаты назначения ТЦЗ при АС, осложненном вторичным АА-амилоидозом. Пациенты и методы. В анализ включено 6 больных АС со вторичным АА-амилоидозом. Все пациенты были мужского пола, позитивные по HLA-B27. Средний возраст больных составил 44±9,2 года, средний возраст дебюта болезни – 16,3±7,9 года, средняя длительность АС – 26,0±7,5 года. Все 6 пациентов имели гистологически подтвержденный вторичный АА-амилоидоз: у всех отмечалось поражение почек, у 5 – также поражение желудочно-кишечного тракта и у 2 – сердца. В качестве первого биологического препарата ТЦЗ был назначен 2 больным, а 4 пациента ранее уже получали один или более ингибитор фактора некроза опухоли α. Средняя длительность лечения ТЦЗ составила 27,6 [3,0; 36,0] мес.Результаты и обсуждение. На фоне терапии ТЦЗ значимо снизились как уровень СРБ (М±σ): с 81,1±74,5 до 1,2±0,8 мг/л (р&lt;0,05) и суточной протеинурии (Ме [25-й; 75-й перцентили]): с 1,8 [1,0; 2,1] до 0,2 [0,1; 0,3] г/сут (р&lt;0,05), так и индексы активности АС – BASDAI (М±σ): с 6,2±1,6 до 3,3±0,9 (р&lt;0,05); ASDAS-СРБ (М±σ) с 4,6±1,1 до 2,04±0,7 (р&lt;0,05). Положительная динамика отмечена и в отношении уменьшения числа больных с воспалительной болью в спине, артритами и кокситом. Описан клинический случай применения ТЦЗ с развитием клинико-лабораторной ремиссии АС.Заключение. Представленные данные показывают, что в определенных клинических ситуациях иИЛ6 могут быть высокоэффективны при АС

Directional Sensitivity of the NEWSdm Experiment to Cosmic Ray Boosted Dark Matter

We present a study of a directional search for Dark Matter boosted forward when scattered by cosmic-ray nuclei, using a module of the NEWSdm experiment. The boosted Dark Matter flux at the edge of the Earth's atmosphere is expected to be pointing to the Galactic Center, with a flux 15 to 20 times larger than in the transverse direction. The module of the NEWSdm experiment consists of a 10 kg stack of Nano Imaging Trackers, i.e.~newly developed nuclear emulsions with AgBr crystal sizes down to a few tens of nanometers. The module is installed on an equatorial telescope. The relatively long recoil tracks induced by boosted Dark Matter, combined with the nanometric granularity of the emulsion, result in an extremely low background. This makes an installation at the INFN Gran Sasso laboratory, both on the surface and underground, viable. A comparison between the two locations is made. The angular distribution of nuclear recoils induced by boosted Dark Matter in the emulsion films at the surface laboratory is expected to show an excess with a factor of 3.5 in the direction of the Galactic Center. This excess allows for a Dark Matter search with directional sensitivity. The surface laboratory configuration prevents the deterioration of the signal in the rock overburden and it emerges as the most powerful approach for a directional observation of boosted Dark Matter with high sensitivity. We show that, with this approach, a 10 kg module of the NEWSdm experiment exposed for one year at the Gran Sasso surface laboratory can probe Dark Matter masses between 1 keV/c$^2$ and 1 GeV/c$^2$ and cross-section values down to $10^{-30}$~cm$^2$ with a directional sensitive search.Comment: 15 pages, 14 figures, updated references, clarified discussion in intro section. Submitted to JCA

SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection