БИОРАСПРЕДЕЛЕНИЕ ПОЛИМЕРНОЙ ТРАНСПОРТНОЙ ФОРМЫ РИФАБУТИНА

Background: One way to increase drug efficacy is to provide a drug delivery transport system to the target organ. A widely used method is to incorporate the drug in a biodegradable polymer composition with forming nanosized drug’s transport forms. Objective: Our aim was to investigate the tissue biodistribution of antibiotic rifabutin transport system based on lactic and glycolic acids copolymer, and to compare it with the pure substance of rifabutin. Methods: These substances were administered to two groups of rats intragastrically in the doses of 10 mg/kg. After a certain period of time, the animals were sacrificed by cervical dislocation. Samples preparation for analysis was carried out of the liquid-liquid extraction. Active substance’s concentrations were measured by high performance liquid chromatography method. Results: The study included 8-week-aged Wistar rats of both sexes weighing 0.22±0.02 kg. Animals were divided into 2 groups. The study group received polymer form of antibiotic, and the comparison group received substance of rifabutin. In intervals of 10 min, 30 min, 1 h, 2 h, 4 h, 7 h, 15 h, 24 h after drug administration liver, lung, spleen, kidney, intestines, stomach, heart and brain were resected respectively. Organs were measured by their weight. The drug was not detected in the brain. Rifabutin was determined in other examined tissues within 10 minutes and the maximum drug concentration in organs was fixed in 1.5–3.5 hours after administration. The rifabutin concentrations defined in the lungs were significantly higher in polymer form (p 0.05). The polymer form’s distribution coefficient was higher in the liver and lungs (15.83 and 10.14 μg/g respectively) in comparison with the substance one. The minimum amount of the active ingredient was observed in the heart (0.02 μg/g). Conclusion: It is shown that the inclusion of the drug in a polymeric form substantially alters its localization in organs and tissues. Extensive biodistribution nanorifabutin in lung tissue, liver and spleen is established.  Одним из направлений увеличения эффективности лекарственных средств является создание транспортной системы доставки лекарств в целевой орган. Широко распространенный методом — включение лекарственного вещества в состав биодеградируемого полимера с образованием наноразмерной транспортной формы лекарства. Цель исследования: изучить биораспределение по тканям транспортной системы антибиотика рифабутина на основе сополимера молочной и гликолевой кислоты, а также сравнить ее с чистой субстанцией рифабутина. Методы: препараты вводили перорально, через атравматический металлический зонд в дозе 10 мг/кг. Далее через определенные промежутки времени экспериментальных животных умерщвляли методом дислокации шейных позвонков. Пробоподготовка органов к анализу осуществлялась жидкость-жидкостной экстракцией. Концентрацию действующего вещества измеряли с использованием метода высокоэффективной жидкостной хроматографии. Результаты: в исследование включали восьминедельных крыс линии Wistar обоего пола массой 0,22±0,02 кг. Животные были разделены на 2 группы. Исследуемая группа получала антибиотик в полимерной форме, а группа сравнения получала субстанцию рифабутина. Через временные интервалы 10 мин, 30 мин, 1 ч, 2 ч, 4 ч, 7 ч, 15 ч, 24 ч после введения препарата производили резекцию печени, легких, селезенки, почек, кишечника, желудка, сердца и мозга, соответственно, и измеряли их массу. В мозге препарат не обнаруживался. В остальных исследуемых тканях рифабутин определялся уже через 10 мин после введения, а максимальная концентрация препарата достигалась в органах спустя 1,5–3,5 ч. Концентрации рифабутина, определяемые в легких, оказались статистически значимо (p 0,05) выше после введения полимерной формы препарата. Коэффициент распределения полимерной формы в печени и легких был максимальным (15,83 и 10,14 мкг/г, соответственно) по сравнению с субстанцией. Минимальное количество (0,02 мкг/г) действующего вещества наблюдали в сердце. Заключение: показано, что включение рифабутина в полимерную форму значительно изменяет его локализацию по органам и тканям. Установлено повышенное накопление нанокомпозиции рифабутина в ткани легких, печени и селезенки.

First experimental results obtained using the highpower free electron laser at the siberian center for photochemical research

The first lasing near the wavelength of 140 µm was achieved in April 2003 using a high-power free electron laser (FEL) constructed at the Siberian Center for Photochemical Research. In this paper we briefly describe the design of the FEL driven by an accelerator–recuperator. Characteristics of the electron beam and terahertz laser radiation, obtained in the first experiments, are also presented in the paper.У Сибірському центрі фотохімічних досліджень навесні 2003 року отримана генерація випромінювання з довжиною хвилі 140 мкм на потужному лазері на вільних електронах (ЛВЕ). У роботі коротко описана конструкція ЛВЕ на базі прискорювача рекуператора і представлені результати вимірювання деяких параметрів електронного пучка і терагерцового випромінювання.В Сибирском центре фотохимических исследований весной 2003 года получена генерация излучения с длиной волны 140 мкм на мощном лазере на свободных электронах (ЛСЭ). В работе кратко описана конструкция ЛСЭ на базе ускорителя рекуператора и представлены результаты измерения некоторых параметров электронного пучка и терагерцового излучения

DIGITAL-ФОРМАТЫ КАК СПОСОБ ПРОДВИЖЕНИЯ АВТОМОБИЛЕЙ В ПЕРИОД ПАНДЕМИИ

The rapid development of new digital and visual technologies is leading to fundamental changes in the field of marketing. Modern car brands that seek to multiply and maintain their established positions in the global car market often face extensive changes in the external environment. The pandemic has affected the way cars are promoted in a total lockdown environment.Быстрое развитие новых цифровых и визуальных технологий приводит к фундаментальным изменениям в области маркетинга. Современные автомобильные бренды, которые стремятся приумножить и сохранить свои сформировавшиеся позиции на мировом рынке автомобилей, зачастую сталкиваются с многочисленными изменениями во внешней среде. Пандемия повлияла на способы продвижения автомобилей в условиях тотального локдауна

Development and validation of atazanavir and ritonavir determination in human plasma by HPLC-MS method

Introduction. HIV infection is one of the most relevant diseases from a medical, epidemiological and social point of view. Timely diagnosis, detection and control of the disease, adequate prescription of antiretroviral therapy can sufficiently reduce the viral load on the patient's body, reduce the risk of transmission of infection. Currently, combinations of various antiretroviral drugs are increasingly being prescribed as therapy. One of the most important is combination of atazanavir and ritonavir. The most important stage for the study of pharmacokinetics, studies of comparative pharmacokinetics and bioequivalence is the development of an analytical method that allows you to determine the investigated substances in human plasma. There are currently no published methods for the determination of atazanavir and ritonavir in human plasma using high performance liquid chromatography with mass selective detection using a single quadrupole mass detector. In this article presents the development and validation of a method for the determination of atazanavir and ritonavir in blood plasma after sample preparation by the method of protein precipitation. Aim. The aim of the study is to develop a method for the quantitative determination of atazanavir and ritonavir in human plasma by HPLC with mass spectrometric detection for performing the analytical part of pharmacokinetic studies. Materials and methods. Determination of atazanavir and ritonavir in human plasma by HPLC with mass spectrometric detection. A sample was prepared using protein deposition. Results and discussion. The method was validated of selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over effect and sample stability. Conclusion. The method of the determination of atazanavir and ritonavir in human plasma was developed and validated by HPLC-MS. The analytical range of the was 50.0–10000.0 ng/mL in plasma for atazanavir and 10.0–2500.0 ng/mL in plasma for ritonavir. Method could be applied to determination of atazanavir and ritonavir in plasma for PK and BE studies. © Komarov T. N., Shohin I. E., Miskiv O. A., Bogdanova D. S., Aleshina A. V., Medvedev Yu. V., Bagaeva N. S., 2020

Alakit and Daldyn kimberlite fields, Siberia, Russia: Two types of mantle sub-terranes beneath central Yakutia?

Mineral data from Yakutian kimberlites allow reconstruction of the history of lithospheric mantle. Differences occur in compositions of mantle pyropes and clinopyroxenes from large kimberlite pipes in the Alakit and Daldyn fields. In the Alakit field, Cr-diopsides are alkaline, and Stykanskaya and some other pipes contain more sub-calcic pyropes and dunitic-type diamond inclusions, while in the Daldyn field harzburgitic pyropes are frequent. The eclogitic diamond inclusions in the Alakit field are sharply divided in types and conditions, while in the Daldyn field they show varying compositions and often continuous Pressure–Temperature (P–T) ranges with increasing Fe# with decreasing pressures. In Alakit, Cr-pargasites to richterites were found in all pipes, while in Daldyn, pargasites are rare Dalnyaya and Zarnitsa pipes. Cr-diopsides from the Alakit region show higher levels of light Rare Earth Elements (LREE) and stronger REE-slopes, and enrichment in light Rare Earth Elements (LREE), sometimes Th-U, and small troughs in Nb-Ta-Zr. In the Daldyn field, the High Field Strength Elements HFSE troughs are more common in clinopyroxenes with low REE abundances, while those from sheared and refertilized peridotites have smooth patterns. Garnets from Alakit show HREE minima, but those from Daldyn often have a trough at Y and high U and Pb. PTXfO2 diagrams from both regions show similarities, suggesting similar layering and structures. The degree of metasomatism is often higher for pipes which show dispersion in P–Fe# trends for garnets. In the mantle beneath Udachnaya and Aykhal, pipes show 6–7 linear arrays of P–Fe# in the lower part of the mantle section at 7.5–3.0 GPa, probably reflecting primary subduction horizons. Beneath the Sytykanskaya pipe, there are several horizons with opposite inclinations which reflect metasomatic processes. The high dispersion of the P–Fe# trend indicating widespread metasomatism is associated with decreased diamond grades. Possible explanation of the differences in mineralogy and geochemistry of the mantle sections may relate to their tectonic positions during growth of the lithospheric keel. Enrichment in volatiles and alkalis possibly corresponds to interaction with subduction-related fluids and melts in the craton margins. Incorporation of island arc peridotites from an eroded arc is a possible scenario