TAAR1-dependent effects of apomorphine in mice.

G protein-coupled trace amine-associated receptor 1 (TAAR1) is expressed in several brain regions and modulates dopaminergic activity partially by affecting D2 dopamine receptor function. In vitro , the nonselective dopamine agonist apomorphine can activate mouse and rat TAAR1. The aim of the present study was to evaluate whether apomorphine activity at the rodent TAAR1 observed in in vitro studies contributes to its behavioral manifestation in mice. For this purpose, we compared the behavioral effects of a wide range of apomorphine doses in wild type (WT) and TAAR1 knockout (TAAR1-KO) mice. Apomorphine-induced locomotor responses (0.01–4.0 mg/kg) were tested in locomotor activity boxes, and stereotypic behavior at 5 mg/kg was tested by ethological methods. A gnawing test was used to analyze the effects of the highest dose of apomorphine (10 mg/kg). No statistically significant differences were observed between TAAR1-KO and WT mice following inhibitory pre-synaptic low doses of apomorphine. At higher doses (2.0–5.0 mg/kg), apomorphine-induced climbing behavior was significantly reduced in TAAR1 mutants relative to WT controls. Moreover, the lack of TAAR1 receptors decreased certain types of stereotypies (as reflected in by measures of the global stereotypy score, licking but not sniffing or gnawing) that were induced by high doses of apomorphine. These data indicate that apomorphine activity at TAAR1 contributes to some behavioral manifestations, particularly climbing, in rodents following high doses of this drug. The contribution of TAAR1 to apomorphine-induced climbing in rodents should be considered when apomorphine is used as a screening tool in the search for potential antipsychotics

SOURCES AND MECHANISMS OF FORMATION OF ALKALINE RARE-METAL GRANITES AT THE ZASHIKHINSKY MASSIF BASED ON GEOCHEMICAL AND Nd ISOTOPE DATA

The intraplate alkaline-granite magmatism essentially contributes to formation of rare-metal strategic raw materials. In the Major Sayan Fault of the East Sayan Mountains, the rocks of the Zashikhinsky (Pz3) massif were studied through the isotope-geochemical analysis to identify probable sources of alkaline-granite magma and mechanisms of their evolution resulting in ore accumulations, up to the formation of Nb-Ta deposits. The Nd isotopic characteristics of its alkaline granites were obtained for the first time. Together with the results of mineralogical and geochemical studies, they were applied for modeling its formation, in which crystallization differentiation of alkaline granite melts proceeds simultaneously with their assimilation of the enclosing granite-metamorphic formations

New insights from old cosmic rays: A novel analysis of archival KASCADE data

Cosmic ray data collected by the KASCADE air shower experiment are competitive in terms of quality and statistics with those of modern observatories. We present a novel mass composition analysis based on archival data acquired from 1998 to 2013 provided by the KASCADE Cosmic ray Data Center (KCDC). The analysis is based on modern machine learning techniques trained on simulation data provided by KCDC. We present spectra for individual groups of primary nuclei, the results of a search for anisotropies in the event arrival directions taking mass composition into account, and search for gamma-ray candidates in the PeV energy domain.Comment: Proceedings of the 37th International Cosmic Ray Conference (ICRC2021), 12-23 July 2021, Berlin, Germany - Onlin

Лізоцимвмісний препарат для сльозозамінної терапії: фармакотерапевтична ефективність

Introduction. The prospective method of dry eye syndrome (DES) is the tear-substitutive therapy with the help of eye drops, among which there are absent such with enzyme lysozyme (EC 3.2.1.17), possessing bacteriolytic,immunostimulating, anti-inflammatory, regenerating, analgetic activity and have the protective function of lacrimal liquid. Because we had developed the preparation with lysozyme, timely for application in such direction and itsophthalmosafety was shown, the investigation of it’s pharmacotherapeutic effectiveness was advisable.The aim of the study – investigation of the pharmaco-therapeutic effectiveness of eye drops “artificial tear” with lysozyme as a potential drug for the dry eye syndrome treatment.Research Methods. The study of the anti-inflammatory and regenerative properties of the produced eye drops with lysozyme was conducted on 6 sexually mature healthy rabbits of the Chinchilla strain with modelled traumatickeratitis.Results and Discussion. Basing on the previously obtained experimental data, the stable, highly active, sterile eye drops “artificial tear” with lysozyme were made for their pharmaco-therapeutic effectiveness investigation on the Chinchilla rabbits with modelled traumatic keratitis. It was shown, that instillations of eye drops "artificial tear" with lysozyme in the treatment of traumatic keratitis have an anti-inflammatory and regenerative effect, helping the more quick liquidation of the inflammation and acceleration of the epithelization process compared with control.Conclusions. For conduction of preclinical research, the highly-active, stable, sterile eye drops “artificial tear” with lysozyme were made. The instillations of the obtained eye drops at treatment of traumatic keratitis renders anti-inflammatory and regenerative effect, helping the more quick liquidation of inflammation and the acceleration of the epithelization process.Вступление. Перспективным методом лечения синдрома сухого глаза является слезозаменительная терапия с помощью глазных капель, среди которых отсутствуют таковые с энзимом лизоцимом (КФ 3.2.1.17), имеющим бактериолитическое, иммуностимулирующее, противовоспалительное, регенерирующее, обезболивающее действие и выполняющим защитную функцию слезной жидкости. Поскольку мы разработали препарат с лизоцимом, актуальный для использования в данном направлении, показали его офтальмобезвредность, целесообразно изучить его  фармакотерапевтическую эффективность.Цель исследования – изучить фармакотерапевтическую эффективность глазных капель “искусственная слеза” с лизоцимом как потенциального препарата для лечения синдрома сухого глаза.Методы исследования. Противовоспалительные и регенераторные свойства изготовленных глазных капель с лизоцимом изучали на 6 половозрелых здоровых кроликах породы Шиншилла с моделированнымтравматическим кератитом.Результаты и обсуждение. На основе ранее полученных экспериментальных данных были изготовлены стабильные, высокоактивные, стерильные глазные капли “искусственная слеза” с лизоцимом для исследования их фармакотерапевтической эффективности на кроликах породы Шиншилла с моделированным травматическим кератитом. Показано, что инстилляции глазных капель “искусственная слеза” с лизоцимом при лечении травматического кератита оказывают противовоспалительное и регенера торное действие, способствуя более быстрой ликвидации воспаления и ускорению процесса эпителизации по сравнению с контролем.Выводы. Для проведения доклинических исследований изготовлены стабильные, высокоактивные, стерильные глазные капли “искусственная слеза” с лизоцимом. Инстилляции полученных глазных капель при лечении травматического кератита оказывают противовоспалительное и регенераторное действие, способствуя более быстрой ликвидации воспаления и ускорению процесса эпителизации.Вступ. Перспективним методом лікування синдрому сухого ока є сльозозамінна терапія за допомогою очних крапель, серед яких відсутні такі з ензимом лізоцимом (КФ 3.2.1.17), що має бактеріолітичну, імуностимулювальну, протизапальну, регенерувальну, знеболювальну дію і виконує захисну функцію слізної рідини. Оскільки ми розробили препарат з лізоцимом, актуальний для використання в даному напрямку, показали його офтальмобезпечність, доцільно вивчити його фармакотерапевтичну ефективність.Мета дослідження – вивчити фармакотерапевтичну ефективність очних крапель “штучна сльоза” з лізоцимом як потенційного препарату для лікування синдрому сухого ока. Методи дослідження. Протизапальні та регенераторні властивості виготовлених очних крапель з лізоцимом вивчали на 6 статевозрілих здорових кролях породи Шиншила з модельованим травматичнимкератитом. Результати й обговорення. На основі раніше отриманих експериментальних даних було виготовлено стабільні, високоактивні, стерильні очні краплі “штучна сльоза” з лізоцимом для дослідження їх фармакотерапевтичної ефективності на кролях породи Шиншила з модельованим травматичним кератитом. Показано, що інстиляції очних крапель “штучна сльоза” з лізоцимом при лікуванні травматичного кератиту чинять протизапальну і регенераторну дію, сприяючи більш швидкій ліквідації запалення таприскоренню процесу епітелізації порівняно з контролем.Висновки. Для проведення доклінічних досліджень виготовлено стабільні, високоактивні, стерильні очні краплі “штучна сльоза” з лізоцимом. Інстиляції отриманих очних крапель при лікуванні травматичного кератиту чинять протизапальну і регенераторну дію, сприяючи більш швидкій ліквідації запалення та прискоренню процесу епітелізації

Radical surgery on the middle ear in the treatment of cholesteatoma: history or reality? A review

Radical surgery on the middle ear is primarily associated with such pathology as cholesteatoma and ear neoplasms. And if in the case of tumors radicalism in ear surgery is justified, then in the surgery of the cholesteatomic process there is a need to discuss this issue. The existence of acquired cholesteatoma was recognized more than three centuries ago. Without timely detection and intervention, cholesteatomas can increase to gigantic sizes and lead to numerous intracranial and extracranial complications. Due to its aggressive growth, invasive nature and potentially fatal consequences of intracranial complications, acquired cholesteatoma remains the cause of morbidity and death in those who do not have access to advanced medical care. Currently, there are no effective non-surgical methods of treatment. The article provides a brief overview of the main issues related to acquired middle ear cholesteatoma, and discusses the practica

Pyroelectric deflector of relativistic electron beam

Deflection of a relativistic electron beam by means of the pyroelectric deflector is demonstrated experimentally for the first time. The operating principle of the pyroelectric deflector is based on the generation of a strong transverse electric field in a vacuum in the gap between a pair of pyroelectric crystals due to the pyroelectric effec

NEW DATA ON THE GEOLOGICAL STRUCTURE OF THE SYNNYR ULTRA-K INTRUSIVE FORMATION

The Synnyrsky massif is the largest intrusive containing ultra-potassium syenites, synnyrites, which are raw materials for the production of potash fertilizers and aluminum. An extensive complex of geological and geochemical studies has been carried out, including exploratory drilling, which was carried out on the massif for the first time. The data obtained made it possible to significantly change the idea of the structure of the massif, including a different look at the regularities of the placement of potash-alumina ores, significantly increasing the ore potential and the reliability of its assessment. The present study discusses the existence within the Synnyrsky complex of the third, previously undetected, large intrusive phase, which has its own geological and geochemical features

10-keV electrons transmission through a set of dielectric macrochannels

The results of the study of the 10-keV electron beam transmission through cylindrical dielectric macrochannels with various lengths. All channels made of polyethylene terephthalate had an identical inner diameter of 1.55 mm and lengths of 20, 30, 35, 40, 45, and 50 mm. The dependence of the current passed through beam channels on their tilt angle relative to the incident electron beam is measure

IMMUNOLOGICAL AND PATHOMORPHOLOGICAL ASPECTS OF EARLY AND LATE PREECLAMPSIA

Preeclampsia (PE) is one of the most common complications of pregnancy, and it can be after 20 weeks of gestation. It ends only with a complete dissection of afterbirth. Traditionally, PE is subdivided into the early one, taking place through 34 weeks of pregnancy (EOPE) and the late one, which is after 34 weeks of gestation (LOPE). Clinical manifestations are similar in both cases however, risk factors and the severity of PE are different . It has been established that EOPE is determined by impaired trophoblast invasion and transformation of the spiral arteries of the uterus in early pregnancy, and late onset of PE is associated with oxidative stress of syncytiotrophoblast, which occurs secondarily, with limited gas exchange and insufficient intake of nutrients. Numerous studies have noted a significant contribution of immune responses to the pathogenesis of preeclampsia, however, the state of B-lymphocytes in EOPE and LOPE has not been studied. A comprehensive assessment of the condition of women with early (up to 34 weeks of pregnancy inclusive) and late (after 34 weeks) development of preeclampsia was carried out, taking into account clinical and anamnestic characteristics, the peculiarities of the formation of the structural components of the placenta, as well as determining the nature of differentiation and functional activity of B-lymphocytes. In peripheral venous blood, the content of CD19+, CD20+, CD19+CD27+IgD±, CD19+CD20- CD38+, CD20+CD5+-cells and serum levels of IL-5, IL-9, IL-13 were examined. Morphological examination included gross description, organometry, survey histology, and transmission electron microscopy. In the group of women with early preeclampsia in history, there were more often perinatal losses, premature births and medical abortions, and in the current pregnancy, intrauterine infection, oligohydramnios, placental insufficiency and fetal growth retardation. With late preeclampsia, metabolic syndrome, anemia, and a history of arterial hypertension were more often observed. In the peripheral blood of all women with preeclampsia, there was an increase in the content of CD20+CD5+-cells in comparison with those in uncomplicated pregnancy, more pronounced in the late onset of preeclampsia. Only in women with early preeclampsia blood levels of CD19+CD20- CD38+ and CD19+CD27+IgD±-cells, IL-5, IL-9 and IL-13 increased. Studies of the placenta in early preeclampsia indicated impaired implantation and pathological placentation with the development of primary placental insufficiency, which becomes chronic. In late preeclampsia, the development of placental insufficiency was determined by chronic disorders of maternal and fetal hemocirculation with increased deposition of fibrin and fibrinoid in the basal lamina and in the zones of villous epithelium necrosis. The study showed that the timing of the manifestation of preeclampsia is determined by the action of factors of the clinical history, structural rearrangements in the placenta and immune responses of B-lymphocytes are closely interrelated

ИСТОЧНИКИ И МЕХАНИЗМЫ ФОРМИРОВАНИЯ ЩЕЛОЧНЫХ РЕДКОМЕТАЛЛЬНЫХ ГРАНИТОВ ЗАШИХИНСКОГО МАССИВА НА ОСНОВЕ ГЕОХИМИЧЕСКИХ И Nd ИЗОТОПНЫХ ДАННЫХ

The intraplate alkaline-granite magmatism essentially contributes to formation of rare-metal strategic raw materials. In the Major Sayan Fault of the East Sayan Mountains, the rocks of the Zashikhinsky (Pz3) massif were studied through the isotope-geochemical analysis to identify probable sources of alkaline-granite magma and mechanisms of their evolution resulting in ore accumulations, up to the formation of Nb-Ta deposits. The Nd isotopic characteristics of its alkaline granites were obtained for the first time. Together with the results of mineralogical and geochemical studies, they were applied for modeling its formation, in which crystallization differentiation of alkaline granite melts proceeds simultaneously with their assimilation of the enclosing granite-metamorphic formations.При формировании месторождений редкометалльного стратегического сырья значимая роль принадлежит проявлениям внутриплитового щелочно-гранитного магматизма. С целью изучения вероятных источников щелочно-гранитных магм и механизмов их эволюции, приводящих к рудным накоплениям, вплоть до образования Nb-Ta месторождений, было проведено изотопно-геохимическое изучение пород Зашихинского массива (Восточно-Саянская зона, Главный Cаянский разлом). Впервые получены Nd изотопные характеристики щелочных гранитов массива, которые в совокупности с результатами проведенных ранее минералогических и геохимических исследований позволили предложить модель его формирования, в которой кристаллизационная дифференциация щелочно-гранитных расплавов происходит одновременно с ассимиляцией ими вмещающих гранитных и гранитно-метаморфических комплексов