Characteristics of the response of the microalga (Dunaliella viridis) to cerium compounds in culture

Recently, nanobiotechnology has been developing intensively; therefore, various properties of nanoparticles, which depend on their origin, concentration, and size, are of interest. It is known that CeO2 nanoparticles cause a positive biological effect. These particles are able to penetrate through biomembranes. At the same time, there are assumptions about a high degree of biological risks when using nanomaterials, and it is obvious that the biosafety of nanomaterials is decisive in the development of new products, including for medicine. The cytotoxicity of samples of cerium salts and cerium dioxide nanoparticles of different sizes was assessed at different concentrations using D. viridis. The cytotoxicity level by morphological and functional disorders of D. viridis was investigated, as determined by the change in cell shape, accumulation of inclusions, loss of flagellum, change in nature and movement, the formation of micro- and macroaggregates by D. viridis cells and exometabolite release. The cytotoxicity coefficient was calculated as a quotient of total detected changes divided by their number. It was shown that cerium salts (cerium (IV) ammonium nitrate and cerium (III) chloride) had pronounced cytotoxicity, which exceeded cytotoxicity values of the control by 7 and 6 times, respectively. Cerium dioxide nanoparticles with a size of 6 nm at a concentration of 0.01 M showed intermediate cytotoxicity, which exceeded control values by 3.5 times, and after the effect of nanoparticles with a size of 2 nm at a concentration of 0.1 M, the cytotoxicity coefficient corresponded to control values. The addition of inactivated blood serum to the incubation mixture resulted in a decreased cytotoxic effect of cerium dioxide. The use of D. viridis as a test system will supplement the arsenal of biotesting tools for nanomaterials and the study of the mechanisms of their effect

Study of intermolecular interactions of antiviral agent tilorone with RNA and nucleosides

Background: While antiviral and interferon-inducing agent tilorone is used as a reactant of a number of popular pharmacological preparations, the molecular mechanisms of its biological antiviral activity are under discussions among the specialists. That is why the molecular level model studies of interactions of tilorone with targeting biomolecules and their components are considered to be urgent and useful for understanding the molecular mechanisms of the agent biological activity. Objectives: The current model study is devoted to mechanistic examining of the intermolecular interactions of tilorone with its possible biomolecular targets which are believed to be nucleic acids and such their components as nucleosides containing purine or pyrimidine nitrogen bases. Materials and methods: The objects of the study are model systems composed of tilorone dihydrochloride (Til•2HCl) and its potential targeting biomolecules: single-stranded RNA (ssRNA) obtained from Saccharomyces cerevisiae yeast or nucleosides - adenosine (Ado), thymidine (Thd), or uridine (Urd). Dynamic light scattering (DLS) measurements aimed at observation of drug-biomolecules aggregation is applied to the system (tilorone+ssRNA) (1:10 molar ratio) in RNA-free phosphate buffered saline solution (with 10% fetal bovine serum). Electrospray ionization (ESI) mass spectrometry is used to examine the intermolecular interactions in the binary (tilorone + nucleoside) (Ado, or Thd, or Urd in 1:10 molar ratio) and triple (tilorone + Ado + Urd) (1:10:10 molar ratio) systems dissolved in polar solvent methanol. Results: The obtained DSL data demonstrate that under conditions similar to the physiological ones, introduction of tilorone into the ssRNA solution results in formation of tilorone+ssRNA aggregates which more than 10 times exceed in size the particles observed in the ssRNA solution itself. The ESI mass spectrometry experiments reveal that while the mass spectra of all studied (tilorone + nucleoside) model systems contain ions characteristic of the individual components of the mixtures, in the spectra of (tilorone + Urd) system the ions of stable ion-molecular clusters of uridine with tilorone dication Urd•Til•2H2+ are recorded. The examining of the three-component model system (tilorone + Ado + Urd) testifies to the selectivity of tilorone binding: while the peak of noncovalent complex of Urd•Til•2H2+ is detected, any peaks of the complexes of Ado with tilorone are not found in the mass spectrum. Conclusions: Formation of large-scale molecular aggregates of tilorone with ssRNA in the solutions which are similar to the physiological solution in physical and chemical characteristics is revealed in the performed DLS investigation. Creation of stable Urd•Til•2H2+ noncovalent complexes in (tilorone + nucleoside) model systems was demonstrated by ESI mass spectrometry, while the complexes of tilorone with Ado and Thd are not detected in the experiments. It testifies to the possibility of formation of stable noncovalent complexes of tilorone with ssRNA and their components in biological systems, and pointed at Urd as one of the potential centers of specific binding of RNA molecules with tilorone

Антивирусное и интерферониндуцирующее действие аминоэтоксидифенилов

Проблематика. Новосинтезованим сполукам 4,4′-біс-(2-R-етокси)біфенілам притаманні як інтеркаляція в ДНК, так і противірусна активність та здатність індукувати інтерферон. Мета дослідження. Визначення антивірусної та інтерфероногенної активності похідних дифенілу – аналогів Аміксину в умовах in vitro. Методика реалізації. У роботі на культурах клітин РST і MDBK в умовах in vitro вивчали противірусну та інтерфероніндукуючу дії нових структурних аналогів Аміксину: 4,4′-біс-(2-диметиламіно-етокси)біфенілу, 4,4′-біс-(2-4-метилпіперидино-етокси)біфенілу та 4,4′-біс-(2-[2-метил-2-(4-метилпіперазин-1-іл)-пропіл]аміно-етокси)біфенілу. Результати дослідження. Показано здатність похідних дифенілу пригнічувати розвиток вірусного цитопатичного ефекту на моделі PST-BBC як при профілактичній, так і при лікувальній схемі введення сполук. На моделі перещеплюваних культур клітин PST показано, що сполуки, як і Аміксин, здатні до індукції інтерферону, а їх перевагою є значно менша токсичність. Висновки. Отримані результати дають змогу розглядати похідні дифенілу як сполуки, що здатні забезпечувати антивірусний захист клітин за рахунок не тільки активації продукції інтерферону, але й інших механізмів, вивчення яких є метою майбутніх досліджень.Background. Synthesized compounds 4,4′-bis(2-R-ethoxy)diphenyl characterized as intercalation into DNA and antiviral activity and ability to induce interferon. Objective. Determine the antiviral activity and interferon inducer actions of diphenyl derivatives -analogues of Amiksin, in terms of in vitro. Methods. The work on cell cultures PST and MDBK in conditions in vitro studied antiviral and interferon inducer of the new structural analogues of Amiksin: 4,4′-bis-(2-dimethylamino-ethoxy)diphenyl, 4,4′-bis-(2-4-metylpiperydynoethoxy)diphenyl and 4,4′-bis-(2-[2-methyl-2-(4-metylpiperazyn-1-yl)-propil]amino-ethoxy)diphenyl. Results. Diphenyl derivatives shown the ability to inhibit the development of viral cytopathic effect on the model PST-BBC as in prophylactic and therapeutic regimens in compounds. In the model of inoculated cell cultures PST shown that compounds like Amiksin capable of inducing interferon, their advantage is much less toxicity. With the introduction of experimental animals experimental compounds IFN gene-active substances have been better than Amiksin. Conclusions. The results can be considered as derivatives of diphenyl compounds that are able to provide virus protection cells not only due to the activation of interferon production, but other mechanisms, the study of which is the goal of future research.Проблематика. Новосинтезированным соединениям 4,4′-бис(2-R-этокси)бифенилам присущи как интеркаляция в ДНК, так и противовирусная активность и способность индуцировать интерферон. Цель исследования. Определение антивирусной и интерфероногенной активности производных дифенила – аналогов Амиксина в условиях in vitro. Методика реализации. В работе на культурах клеток PST и MDBK в условиях in vitro изучали противовирусное и интерферониндуцирующее действия новых структурных аналогов Амиксина: 4,4′-бис(2-диметиламино-этокси)бифенила, 4,4′-бис(2-4-метилпиперидино-этокси)бифенила и 4,4′-бис-(2-[2-метил-2-(4-метилпиперазин-1-ил)-пропил]амино-этокси)бифенила. Результаты исследования. Показана способность производных дифенила подавлять развитие вирусного цитопатического эффекта на модели PST-BBC как при профилактической, так и при лечебной схеме введения соединений. На модели перевиваемых культур клеток PST показано, что соединения, как и Амиксин, способны к индукции интерферона, а их преимуществом является значительно меньшая токсичность. Выводы. Полученные результаты позволяют рассматривать производные дифенила как соединения, способные обеспечивать антивирусную защиту клеток за счет не только активации продукции интерферона, но и других механизмов, изучение которых является целью будущих исследований

Синтез і цитотоксичність аміноетоксидифенілів

The implementation mechanism of the antiviral activity (AA) and interferon induction (IFI) by planar polycyclic compounds has not yet been determined. However, our hypothesis of the priority role of intercalation in double strand nucleic acids (NA) has gained strong arguments in its favour in our works and the works of foreign colleagues.On the other hand, the presence of AA and the ability to induce IFI in biphenyl derivatives that are incapable to intercalate in NA indicates the possibility of implementing alternative mechanisms. This determined our interest to the study of aminoethoxydiphenyls (AED), which synthesis and investigation of cytotoxicity become the subject of this article. 4,4’-Bis-(2-chloroethoxy)diphenyl was obtained by alkylation of dihydroxydiphenyl with dichloroethane in its mixture with aqueous sodium hydroxide (20%) in the presence of tetrabutylammonium chloride (TBAC). Series of AED were synthesized by substitution of chlorine by iodine in the mixture of xylene with the aqueous solution of sodium iodide in the presence of TBAC with subsequent amination with primary and secondary amines. The protonated molecular ions (MI) intensive peaks of the compounds synthesized are observed in the mass spectra with FAB ionization. The most common way of MI fragmentation is PhO-CH2-bond cleavage following the side aminoalkyl fragment detachment. Absorption bands typical for CH (arom.), CH (aliph.), COC bonds and NH protonated terminal amino groups are present in IR spectra. In the 1H-NMR spectra signals from aromatic and aliphatic protons present, multiplicity and integral intensity correspond to the attributed structures. Cytotoxicity of the compounds synthesized was tested using EPT cells in vitro. All AED tested appeared to be comparable to amixine and are in the range from low to moderate cytotoxicity.Механизм реализации противовирусной активности (ПА) и индукции индерферона (ИФН) планарными полициклическими соединениями до сих пор не установлен, хотя выдвинутая нами гипотеза о приоритетной роли интеркаляции в двухспиральные нуклеиновые кислоты (НК) получила весомые аргументы в свою пользу в наших работах и работах зарубежных коллег. С другой стороны, наличие ПА и способности индуцировать ИФН в производных дифенила, не способных к интеркаляции в НК, указывает на возможность реализации альтернативных механизмов. Это и определило наш интерес к развернутому исследованию аминоалкоксидифенила (ААД), началу которого – синтезу и исследованию цитотоксичности ААД и посвящена эта статья. Алкилированием дигидроксибифенила дихлорэтаном в смеси водного раствора гидроксида натрия (20%) с 1,2-дихлорэтаном в присутствии тетрабутиламмония хлорида (ТБАХ) получен 4,4’-бис-(2-хлороэтокси) бифенил. Замену хлора на йод проводили в смеси ксилола с водным раствором йодида натрия в присутствии ТБАЙ с последующим аминированием рядом первичных и вторичных аминов; синтезирован ряд АЭД. В масс-спектрах с ионизацией БУА синтезированных соединений имеются интенсивные пики протонированных молекулярных ионов (МИ), наиболее типичным путем фрагментации МИ является разрыв связи PhO-CH2 с отщеплением бокового аминоалкильного фрагмента. В ИК-спектрах наблюдаются полосы поглощения, характерные для связей CH (аром.), CH (алиф), COC и NH протонованных терминальных аминогрупп. В спектрах 1H-ЯМР имеются сигналы от ароматических и алифатических протонов, мультиплетность и интегральная интенсивность которых соответствуют приписываемым структурам. На клетках ПТП изучена цитотоксичность ряда 4,4’-бис-(2-аминоэтокси)дифенилов, значения сопоставимы с цитотоксичностью амиксина и находятся в диапазоне от низких до умеренных.Механізм реалізації противірусної активності (ПА) та індукції інтерферону (ІФН) планарними поліциклічними сполуками досі не встановлено, хоча висунута нами гіпотеза про пріоритетну роль інтеркаляції в двоспіральні нуклеїнові кислоти (НК) набула вагомих аргументів на свою користь в наших роботах та роботах іноземних колег. З іншого боку, наявність ПА та здатності індукувати ІФН у похідних дифенілу, не здатних до інтеркаляції у НК, вказує на можливість реалізації альтернативних механізмів. Це й спричинило наш інтерес до поглибленого дослідження аміноалкоксидифенілів (АЕД), початку якого – синтезу та дослідженню цитотоксичності АЕД і присвячена ця стаття. Алкілуванням дигідроксибіфенілу дихлороетаном у суміші водного розчину гідроксиду натрію (20%) з 1,2-дихлороетаном у присутності тетрабутиламонію хлориду (ТБАХ) отримано 4,4’-біс-(2-хлороетокси)біфеніл. Заміну хлору на йод проводили в суміші ксилолу з водним розчином йодиду натрію в присутності ТБАЙ з наступним амінуванням низкою первинних та вторинних амінів; синтезована низка АЕД. В мас-спектрах з іонізацією БПА синтезованих сполук наявні інтенсивні піки протонованих молекулярних іонів (МІ), найбільш типовим шляхом фрагментації МІ є розрив зв’язку PhO–CH2 з відщепленням бокового аміноалкільного фрагменту. В ІЧ-спектрах наявні смуги поглинання, характерні для зв’язків C-H (аром.), C-H (аліф), C-O-C та NH протонованих термінальних аміногруп. У спектрах 1H-ЯМР наявні сигнали від ароматичних та аліфатичних протонів, мультиплетність та інтегральна інтенсивність яких відповідає приписуваним структурам. На клітинах ПТП вивчена цитотоксичність низки 4,4’-біс-(2-аміноетокси)дифенілів, значення якої зіставні з токсичністю аміксину та знаходяться в діапазоні від низьких до помірних

Антивирусная и интерферониндуцирующая активность новых соединений – производных индолхиноксалинов

Проблематика. Розробка нових препаратів з антивірусною активністю та здатністю індукувати інтерферон є актуальним завданням з огляду на стрімке поширення вірусних інфекцій, формування резистентних до існуючих антивірусних препаратів штамів вірусів, загальне зниження імунної відповіді. Мета дослідження. Визначення антивірусної та інтерфероногенної активності похідних індолохіноксалінів в умовах in vitro. Методика реалізації. У роботі в умовах in vitro на перещеплюваній культурі клітин ST вивчали антивірусну та інтерфероніндукуючу дію 18 нових новосинтезованих сполук – похідних індолохіноксалінів. Результати дослідження. Показано здатність досліджуваних речовин пригнічувати розвиток вірусного цитопатичного ефекту на моделі ST-BBC тільки при лікувальній схемі введення. На моделі перещеплюваних культур клітин ST показано, що 12 із 18 досліджених сполук у концентраціях 0,1–0,2 мкг/мл здатні до індукції ІФН. Висновки. Серед досліджених сполук – похідних індолохіноксаліну як перспективну для подальших досліджень визначено сполуку RG-61, яка проявляє низьку токсичність (порівняно зі сполуками низки похідних) і антивірусну активність у інфікованих клітинах, а також здатна до індукції ІФН.Background. The development of new drugs with antiviral activity and the ability to induce interferon is an urgent task, taking into account the rapid spread of viral infections, development of resistance the virus strains to existing antiviral drugs and the overall decline of the immune response. Objective. Determine the antiviral activity and interferon inducer actions of indolequinoxalines derivatives in terms of in vitro. Methods. The work on PST cell cultures in conditions of in vitro antiviral and interferon inducer of the 18 new indolequinoxalines derivatives was studied. Results. The ability of indolequinoxalines derivatives to inhibit the development of viral cytopathic effect on the model PST-BBC only in therapeutic regimens was shown. In the model of inoculated cell cultures PST is shown that 12 compounds are capable of inducing interferon in low concentrations. Conclusions. Among the indolequinoxalines derivatives RG-61 compound as a promising for further studies was identified, which has a low toxicity (as compared to a number of compounds derived), has antiviral activity in infected cells and is capable of inducing IFN.Проблематика. Разработка новых препаратов с антивирусной активностью и способностью индуцировать интерферон является актуальной задачей с учетом стремительного распространения вирусных инфекций, формирования резистентных к существующим антивирусным препаратам штаммов вирусов, общего снижения иммунного ответа. Цель исследования. Определение антивирусной и интерфероногенной активности производных индолохиноксалинов в условиях in vitro. Методика реализации. В работе на культурах клеток ST в условиях in vitro изучали противовирусное и интерферониндуцирующее действие 18 новых новосинтезированных соединений – производных индолохиноксалинов Результаты исследования. Показана способность исследуемых веществ подавлять развитие вирусного цитопатического эффекта на модели ST-BBC только при лечебной схеме введения. На модели перевиваемых культур клеток ST показано, что 12 из 18 исследованных соединений вызывают индукцию ИФН в достаточно низких концентрациях. Выводы. Среди исследованных соединений производных индолохиноксалина как перспективное для дальнейших исследований определено соединение RG-61, которое проявляет низкую токсичность (по сравнению с соединениями ряда производных) и антивирусную активность в инфицированных клетках, а также индуцирует ИФН

EPMA-World Congress 2015: Bonn, Germany. 3-5 September 2015

Table of contents A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma Jella-Andrea Abraham, Olga Golubnitschaja A2 Integrated market access approach amplifying value of “Rx-CDx” Ildar Akhmetov A3 Disaster response: an opportunity to improve global healthcare Russell J. Andrews, Leonidas Quintana A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy Russell J. Andrews A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari A6 Specific diets for personalised treatment of diabetes type 2 Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko A7 Towards personalized physiotherapeutic approach Joanna Bauer, Ewa Boerner, Halina Podbielska A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu A10 PPPM in cardiovascular medicine in 2015 Hans-Peter Brunner-La Rocca A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak A12 Ultrasound diagnosis for diabetic neuropathy - comparative study Rostyslav V. Bubnov, Tetyana V. Ostapenko A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer John Paul Cauchi A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well? Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov A16 Survey of questionnaires for evaluation of the quality of life in various medical fields Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska A17 Personalized molecular treatment for muscular dystrophies Sebahattin Cirak A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani A21 Mental indicators at young people with attributes hypertension and pre-hypertension Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon? Shantanu Girotra, Olga Golubnitschaja A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch A27 Immunohistochemical assessment of APUD cells in endometriosis Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver A32 The correlation of dietary habits with gingival problems during menstruation Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara A35 Metabolic hallmarks of cancer as targets for a personalized therapy John Ionescu A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva A37 Challenges in diabetic macular edema Tatjana Josifova A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola A39 EPMA initiative for effective organization of medical travel: European concepts and criteria Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja A40 Design and innovation in e-textiles: implications for PPPM Anthony Kent, Tom Fisher, Tilak Dias A41 Biobank in Pilsen as a member of national node BBMRI_CZ Judita Kinkorová, Ondřej Topolčan A42 Big data in personalized medicine: hype and hope Matthias Kohl A43 The 3P approach as the platform of the European Dentistry Department (DPPPD) Anatoly A. Kunin, Natalia S. Moiseeva A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka A47 Targeting "disease signatures" towards personalized healthcare Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin A50 The use of LED radiation in prevention of dental diseases Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban A53 Maximal aerobic capacity - important quality marker of health Jaroslav Novák, Milan Štork, Václav Zeman A54 The EMPOWER project: laboratory medicine and Horizon 2020 Wytze P. Oosterhuis, Elvar Theodorsson A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta A57 MCI or early dementia predictive speech based diagnosis techniques Matus Pleva, Jozef Juhar A58 Personalized speech based mobile application for eHealth Matus Pleva, Jozef Juhar A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan A61 Sleep apnea and sleep fragmentation contribute to brain aging Kneginja Richter, Lence Miloseva, Günter Niklewski A62 Personalised approach for sleep disturbances in shift workers Kneginja Richter, Jens Acker, Guenter Niklewski A63 Medical travel and innovative PPPM clusters: new concept of integration Olga Safonicheva, Vincenzo Costigliola A64 Medical travel and women health Olga Safonicheva A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery Maxim Sautin, Janna Sinelnikova, Sergey Suchkov A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany Songül Secer, Stephan von Bandemer A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine Niva Shapira A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva A69 Use of specially treated composites in dentistry to avoid violations of aesthetics Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva A70 National eHealth system – platform for preventive, predictive and personalized diabetes care Ivica Smokovski, Tatjana Milenkovic A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. Implications in the context of Preventive, Predictive, and Personalized Medicine Arturo Solís-Herrera, María del Carmen Arias-Esparza, Sergey Suchkov A73 Plurality and individuality of hepatocellular carcinoma: PPPM perspectives Krishna Chander Sridhar, Olga Golubnitschaja A74 Strategic aspects of higher medical education reforms to secure newer educational platforms for getting biopharma professionals matures Maria Studneva, Sihong Song, James Creeden, Мark Мandrik, Sergey Suchkov A75 Overview of the strategies and activities of the European Federation of Clinical Chemistry and Laboratory Medicine, (EFLM) Elvar Theodorsson, EFLM A76 New spectroscopic techniques for point of care label free diagnostics Syed A. M. Tofail A77 Tumor markers for personalized medicine and oncology - the role of Laboratory Medicine Ondřej Topolčan, Judita Kinkorová, Ondřej Fiala, Marie Karlíková, Šárka Svobodová, Radek Kučera, Radka Fuchsová, Vladislav Třeška, Václav Šimánek, Ladislav Pecen, Jan Šoupal, Štěpán Svačina2 A78 Modern medical terminology (MMT) as a driver of the global educational reforms Evgeniya Tretyak, Maria Studneva, Sergey Suchkov A79 Juvenile hypertension; the relevance of novel predictive, preventive and personalized assessment of its determinants Francesca M. Trovato, G. Fabio Martines, Daniela Brischetto, Daniela Catalano, Giuseppe Musumeci, Guglielmo M. Trovato A80 Proteomarkers Biotech George Th. Tsangaris, Athanasios K. Anagnostopoulos A81 Proteomics and mass spectrometry based non-invasive prenatal testing of fetal health and pregnancy complications George Th. Tsangaris, Athanasios K. Anagnostopoulos A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH) José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project) José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents Igor Volchek, Nina Pototskaya, Andrey Petrov A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening Igor Volchek, Nadezhda Pototskaya, Andrey Petrov A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag A87 Sub-optimal health management – global vision for concepts in medical travel Wei Wang A88 Sub-optimal health management: synergic PPPM-TCAM approach Wei Wang A89 Innovative technologies for minimal invasive diagnostics Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger A90 Rare disease diobanks for personalized medicine Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare Disease

The effect of antiviral substance 6-(2-morpholin-4-yl-ethyl)-6H-indolo [2,3-b]quinoxaline upon biomarkers of inflammation

Aim. To investigate changes in pro-inflammatory status of laboratory rats after introduction of antiviral substances with interferon-inducing action: 6-(2-morpholin-4-yl-ethyl)-6H-indolo[2,3-b]quinoxaline and tilorone. Methods. MCP-1 content, blood leukocyte counts and functional activity of phagocytes were measures using flow cytometry techniques. Complement content was determined in microtest based upon hemolysis of sensitized erythrocytes. Results. Both oral and intraperitoneal applications of the substances were characterized by an elevation in monocytic counts, potentiated metabolic reserve of phagocytic cells, increased MCP-1 and complement content in serum. In contrast to tilorone, after introduction of 6-(2-morpholin-4-yl-ethyl)-6H-indolo[2,3-b]quinoxaline substantial raise in circulating neutrophil counts and their phagocytic activity was not determined, while MCP-1 and complement responses were significantly lower compared to reference substance. Conclusion. Although both substances are IFN-inducers with pluripotent immunostimulatory action, the tested derivative was characterized by a less pronounced elevation of complement activity, MCP-1 content and neutrophil counts. This implies that application of 6-(2-morpholin-4-yl-ethyl)-6H-indolo[2,3-b]quinoxaline can strengthen innate antiviral resistance with minimized risks of potential autoimmunological adverse effects

Nanoparticles of Cerium Dioxide – an Effective Antiviral Agent and Adjuvant of Biologically Active Molecules

There was studied the influence of cerium dioxide nanoparticles on the cytokines production in the conditions of their application in the composition with interferon and as an independent drug. Applying the CDN in combination with IFN showed an increased interferon response of experimental mice compared with unmodified IFN. IFN-CDN nanobiocomplex does not increase the level of TNF production, which indirectly indicates the safety of the applying of such complex. There was studied the effect of CDN as a therapeutic agent on the cytokines production in the treatment of modeled herpes simplex virus-1 infection. It was found that CDN is able to increase IFN and TNF levels and prolong their effects. It was found that NDC is able to increase the level of IFN and FNP and prolong their effects. The application of CDN caused increasing of TNF levels and their prolonging action. There was shown the significant increasing (to three weeks) in IFN titers on the step of decreasing in TNF titers in the group, that was infected and then treated with NCD. In the non-treated group and in the aciclovir-treated animal group, IFN titers were significantly lower.The obtained results testify to the effectiveness of NDC as a modifying agent for interferon and as a promising agent for the treatment of systemic herpetic infectio