Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

The Concept of a Research Reactor of Small Power for Isotope Processing

The concept of a low-power research reactor for the production of radioisotopes is proposed, the results of calculations of the neutron-physical parameters of the core are presented, which can be used to substantiate the claimed reactor characteristics. In this article, the characteristics of the core of a research reactor of low power is substantiated, the main purpose of which is the production of radioisotope products for medical purposes. Nuclear medicine is one of the most advanced and demanded in the world of modern high-tech medicine, based on the using of atomic nucleus properties. As a rule, atoms with unstable nuclei are radionuclides. The reactor method of radionuclide production allows obtaining large quantities of radioisotope products at a relatively low price, but the reactor base is currently rather limited.     Keywords: radioisotope products, research reactors, neutron-physical characteristic

Developing the Skills of the Future of Students through Non-Formal Education Programs at the University

Статья посвящена вопросам формирования и развития навыков будущего студентов образовательных организаций высшего образования. Показана необходимость формализации требований работодателей к выпускникам университетов через составление исчерпывающего перечня универсальных компетенций, которые должны быть сформированы у выпускников. Приведен опыт НИТУ «МИСиС» по формированию универсальных компетенций студентов путем реализации различных программ неформального образования.The article is devoted to the formation and development of future skills of students of educational organizations of higher education. The need to formalize the requirements of employers for university graduates through the compilation of an exhaustive list of universal competencies that should be formed by graduates is shown. The experience of NUST “MISIS” on formation of universal competencies of students through implementation of various programs of non-formal education is presented

Synthesis and Antimicrobial Activity of New Dialkyl(diaryl)-2-(5-chloro-2-hydroxyphenyl)-2-(phenylethenyl)pentylphosphonium Salts

© 2018, Pleiades Publishing, Ltd. New dialkyl(diaryl)-2-(5-chloro-2-hydroxyphenyl)-2-(phenylethenyl)pentylphosphonium salts bearing various substituents at the phosphorus atom were synthesized. Antimicrobial activity of the salts obtained was estimated. Derivatives with 2-methoxyphenyl substituents at the phosphorus atom are most active against grampositive bacteria. Herewith, dibenzyl-substituted phosphonium derivatives possess the best antifungal activity

ЭФФЕКТИВНОСТЬ ИНГАЛЯЦИОННОЙ ИММУНОТЕРАПИИ РУЗАМОМ У БОЛЬНЫХ АТОПИЧЕСКОЙ БРОНХИАЛЬНОЙ АСТМОЙ: ВЛИЯНИЕ НА ЧАСТОТУ РЕСПИРАТОРНЫХ ИНФЕКЦИЙ И ОБОСТРЕНИЙ

The aim of this study was to investigate efficacy and safety of inhalational treatment with Ruzam in 63 adult patients with persistent mild to moderate atopic bronchial asthma (BA). In this placebo controlled trial, clinical, functional and laboratory parameters were assessed at the end of 2-week treatment with Ruzam and in 6 months after the treatment. All patients also received inhaled corticosteroids. In patients treated with Ruzam, asthma symptoms, bronchial hyperresponsiveness and nitric oxide in the exhaled air decreased and morning PEF increased when compared to patients treated with inhaled corticosteroids plus placebo. During 6 months after the treatment, there were no asthma exacerbations in the Ruzam group and asthma was well-controlled in these patients. The patients treated with Ruzam significantly decreased a frequency of acute respiratory infections. In the control group (n = 32), exacerbation frequency and asthma control level remained unchanged compared to baseline. Achieving clinical control of asthma in Ruzam group was accompanied by a significant reduction in concentrations of inflammatory markers (IFN-γ, ECP) in serum and in the induced sputum that could be used as a measure of systemic anti-inflammatory effect of Ruzam.Проведено плацебо-контролируемое исследование по изучению эффективности и безопасности терапии с применением ингаляционной формы препарата Рузам у взрослых больных атопической бронхиальной астмой (БА) персистирующего легкого и среднетяжелого течения. Клиникоункциональные и лабораторные параметры эффективности оценивались сразу и через 6 мес. после окончания 2-недельного курса иммунотерапии Рузамом у взрослых больных (n = 63). Выявлено уменьшение симптомов БА, повышение утренней пиковой скорости выдоха и порога бронхиальной гиперреактивности, снижение уровня оксида азота в выдыхаемом воздухе (NОex) у больных, получавших ингаляционную терапию Рузамом в комплексе с базисной терапией ингаляционными глюкокортикостероидами (иГКС), по сравнению с контрольной группой больных, получавших только базисную терапию иГКС + плацебо. В течение 6 мес. после окончания курса лечения Рузамом у больных (n = 30) не наблюдалось обострений и сохранялся клинико-функциональный контроль над БА. Отмечено, что у пациентов, получавших Рузам, значимо снизилась частота острых респираторных инфекций. В контрольной группе (n = 32) частота обострений и уровень контроля над БА остались прежними. Достижение клинического контроля над БА у больных, лечившихся Рузамом, сопровождалось достоверной положительной динамикой маркеров воспаления (интерферон (IFN)-γ, эозинофильный катионный протеин) в сыворотке крови и в супернатанте индуцированной мокроты, что может свидетельствовать о системном противовоспалительном влиянии Рузама

Numerical Examination of the Stability of an Exact Two-dimensional Solution for Flux Pile-up Magnetic Reconnection

The Kelvin--Helmholtz (KH) and tearing instabilities are likely to be important for the process of fast magnetic reconnection that is believed to explain the observed explosive energy release in solar flares. Theoretical studies of the instabilities, however, typically invoke simplified initial magnetic and velocity fields that are not solutions of the governing magnetohydrodynamic (MHD) equations. In the present study, the stability of a reconnecting current sheet is examined using a class of exact global MHD solutions for steady state incompressible magnetic reconnection, discovered by Craig & Henton. Numerical simulation indicates that the outflow solutions where the current sheet is formed by strong shearing flows are subject to the KH instability. The inflow solutions where the current sheet is formed by a fast and weakly sheared inflow are shown to be tearing unstable. Although the observed instability of the solutions can be interpreted qualitatively by applying standard linear results for the KH and tearing instabilities, the magnetic field and plasma flow, specified by the Craig--Henton solution, lead to the stabilization of the current sheet in some cases. The sensitivity of the instability growth rate to the global geometry of magnetic reconnection may help in solving the trigger problem in solar flare research.Comment: Accepted for publication in ApJ. Associated movie files and a PDF with high-resolution figures are available at http://www.pha.jhu.edu/~shirose/Craig

Исследование сегнетоэлектрических нанокомпозитов на основе P(VDF-TrFE) методами сканирующей зондовой микроскопии

Ceramic and polymer based nanocomponents combine the properties of their constituents, e.g. flexibility, elasticity, polymer reprocessability, hardness typical of glass, wear resistance and high light refraction index. This helps improving many properties of the materials in comparison with the source components. Since recently researchers have been manifesting interest to the properties of complex composite compounds. This is primarily caused by the unique properties of their structures as compared with conventional materials having homogeneous composition. Secondly, this interest is caused by the fact that these compounds may prove to be much cheaper than homogeneous structures provided the physical properties of the composite in a preset range of parameters (temperature, applied field frequency etc.) are identical to those of the respective homogeneous materials. For example, polyvinyl idenfluoride (PVDF) type ferroelectric polymers and copolymers on its basis have found wide application for functional elements of various electromechanic devices in advanced electronics due to their relatively good piezoelectric and pyroelectric properties. The strong random polarization and the formation of polar non-centrosymmetric crystals provide for the high piezoelectric and pyroelectric activity in these crystals. Scanning probe microscopy has been used for study of ferroelectric nanocomposites having different compositions. The matrix specimen for study of local polarization switching at a nanoscale level was vinyl idenfluoride and trifluoroethylene P(VDF-TrFE) copolymer possessing sufficiently high crystallinity. The composite fillers were barium titanate BaTiO3 and deuterized triglycinsulfate DTGS ferroelectric powders and zirconate-titanate lead barium BPZT ceramic powder. We show these materials to show good promise for use in memory cells.Нанокомпозиты на основе керамики и полимеров сочетают в себе качества составляющих их компонентов: гибкость, упругость, перерабатываемость полимеров и характерные для стекол твердость, устойчивость к износу, высокий показатель светопреломления. Благодаря этому улучшаются многие свойства материалов по сравнению с исходными компонентами. В последнее время исследователи проявляют большой интерес к изучению свойств сложных композитных соединений. Во-первых, это связано с уникальными свойствами таких структур по сравнению с «обычными», однородными по составу веществами.  Во-вторых, — с  тем, что подобные соединения могут оказаться значительно более дешевыми, чем однородные структуры, при условии, что композит по ряду физических показателей и в диапазоне заданных параметров (температуры, частоты приложенного поля и т.д.) идентичен однородным веществам. Так, сегнетоэлектрические полимеры типа поливинилиденфторида (PVDF) и сополимеры на его основе нашли широкое применение в качестве функциональных элементов различных электротехнических устройств в современной электронике за счет своих относительно высоких пьезоэлектрических и пироэлектрических свойств. Высокая спонтанная поляризация и образование полярных нецентросимметричных кристаллов обуславливают появление в этих материалах высокой пьезо- и пироактивности. Методами сканирующей зондовой микроскопии исследованы сегнетоэлектрические нанокомпозиты различных составов. В качестве образца-матрицы для исследования локального переключения поляризации на наномасштабе был выбран сополимер винилиденфторида с трифторэтиленом P(VDF-TrFE), обладающий достаточно высокой долей кристалличности. В качестве наполнителя для композита выбраны порошки сегнетоэлектриков титаната бария BaTiO3 и дейтерированного триглицинсульфата DTGS, керамический порошок цирконата-титаната бария свинца BPZT. Показано, что эти материалы являются перспективными для использования в качестве элементов памяти.

Steatosis drives monocyte-derived macrophage accumulation in human metabolic dysfunction-associated fatty liver disease

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear. METHODS: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. Mouse models of hepatic steatosis were used to investigate observations made from human liver tissue. RESULTS: We observed variable degrees of liver steatosis with minimal fibrosis in our participants. Single-cell RNA sequencing revealed four macrophage clusters that exist in the human fatty liver encompassing Kupffer cells and monocyte-derived macrophages (MdMs). The genes expressed in these macrophage subsets were similar to those observed in mouse models of MAFLD. Hepatic CD14 CONCLUSIONS: The human liver in MAFLD contains macrophage subsets that align well with those that appear in mouse models of fatty liver disease. Recruited myeloid cells correlate well with the degree of liver steatosis in humans. MdMs appear to participate in lipid uptake during early stages of MALFD. IMPACT AND IMPLICATIONS: Metabolic dysfunction associated fatty liver disease (MAFLD) is extremely common; however, the early inflammatory responses that occur in human disease are not well understood. In this study, we investigated macrophage heterogeneity in human livers during early MAFLD and demonstrated that similar shifts in macrophage subsets occur in human disease that are similar to those seen in preclinical models. These findings are important as they establish a translational link between mouse and human models of disease, which is important for the development and testing of new therapeutic approaches for MAFLD

Subclinical Hypothyroidism after Radioiodine Exposure: Ukrainian–American Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident (1998–2000)

BackgroundHypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (131I). Data on risk of hypothyroidism from low to moderate 131I thyroid doses are limited and inconsistent.ObjectiveThis study was conducted to quantify the risk of hypothyroidism prevalence in relation to 131I doses received because of the Chornobyl accident.MethodsThis is a cross-sectional (1998-2000) screening study of thyroid diseases in a cohort of 11,853 individuals < 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum.ResultsMean age at examination of the analysis cohort was 21.6 years (range, 12.2-32.5 years), with 49% females. Mean 131I thyroid dose was 0.79 Gy (range, 0-40.7 Gy). There were 719 cases with hypothyroidism (TSH > 4 mIU/L), including 14 with overt hypothyroidism. We found a significant, small association between (131)I thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03-0.21). EOR per gray was higher in individuals with ATPO < or = 60 U/mL compared with individuals with ATPO > 60 U/mL (p < 0.001).ConclusionsThis is the first study to find a significant relationship between prevalence of hypothyroidism and individual (131)I thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies