Atypical hyperplasias of the breast

The paper describes different types of atypical hyperplasia of the breast. It analyzes numerous works dealing with the evaluation of atypical ductal and lobular hyperplasias as a risk factor for breast cancer. The similar analysis has been also carried out in a cohort of women with a family history. The current capabilities of visual, cytological, morphological, and molecular biological diagnosis of atypical hyperplasias are considered. Modern-day guidelines for the treatment policy and monitoring of treated patients are given. The role and place of different chemoprevention options for this cohort of patients are considered. Whether preventive surgery may and should be performed particularly in a cohort of women with a family history is determined

Composition based on aluminum oxide and polydimethylsiloxane matrix for enhancing drug targeting

Methodological approaches developed at Research Institute of Clinical and Experimental Lymphology for a number of years allow formulating the importance of embedding active pharmaceutical ingredients (API) in the structure of porous carriers (sorbents). The composition of the carrier and API is an enteral system for prolonged dosing of pharmacological agents, which allows providing a specific pharmacological effect and safety of use. The pores of the media (sorbents) act as containers for API. This is especially important for rapidly absorbed drugs, which include, for example, lithium preparations that are used in narrow concentration limits due to their side effects. At the moment, an innovative technology for creating new medicines with an improved combination of efficiency and safety (pharmacological upgrade) has been developed and implemented. The essence of the technology is to create a composition of aluminum oxide and polydimethylsiloxane (matrix) and an active pharmacological ingredient (API). A study of two drugs based on matrix / lithium citrate and matrix / melatonin showed continued specific pharmacological activity of API, better pharmacokinetics, and better safety parameters. The matrix of aluminum oxide and polydimethylsiloxane provides an upgrade of the pharmacological properties of drugs for the dosed and safe delivery of API to the zone of their therapeutic effect

Silver containing sorbents: Physicochemical and biological properties

New silver containing sorbents, based on mineral carriers, such as alumina and silica systems with a meso- and macro- porous structure, have a higher mechanical resistance and, hydrophilic and hydrophobic chemical composition of the surface. These sorbents are easy to find and relatively inexpensive, compared to their known equivalents. They are furthermore characterised by high specific surface and simple preparation, whilst the addition of silver considerably increases their antiseptic activity. The results of research of the physical, chemical and biological properties of the developed substances, as well as bio-comparability of sorbents with biological tissues, are presented in this paper. The modified material acts simultaneously as the carrier for active substances to the area of therapeutic application and as a sorbent used to remove toxic agents from such areas. This approach led us to modify the sorbent, and prolong the delivery of substances such as silver, as an effective antibacterial and antimycotic agent

ANALYSIS OF THE RESULTS OF NEODJUVANT TREATMENT IN PATIENTS WITH CONSIDERATION FOR THE IMMUNOPHENOTYPICAL FEATURES OF BREAST CANCER

The efficiency of neoadjuvant chemotherapy is directly related to the expression of CD95 (FAS/APO-1) apoptosis receptor on cancer cells, which is confirmed with the pathomorphism and changes of CD95-positive cells during neoadjuvant chemotherapy (the most effective CAF regimen is cyclophosphan, doxorubicin, and 5- fluorouracil)

The expression of apoptosis-regulating proteins Bcl-2 and Bad in liver cells of C57Bl/6 mice under light-induced functional pinealectomy and after correction with melatonin

The presence of humans and animals under long-term continuous lighting leads to a suppression of melatonin synthesis, that is, to light-induced functional pinealectomy (LIFP), and the development of desynchronosis. To create LIFP, C57Bl/6 mice were kept under 24-hour lighting (24hL) for 14 days. The animals in the control group were kept under standard lighting conditions. In the next series of experiments, mice with LIFP received daily intragastrically either melatonin (1 mg/kg body weight in 200 μl of distilled water) or 200 μl of water as a placebo. The comparison group consisted of intact animals that received placebo under standard lighting conditions. Immunohistochemical analysis (using an indirect avidin-biotin peroxidase method) revealed the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in sinusoid liver cells (a heterogeneous population consisting of the endotheliocytes, Kupffer cells, Ito cells, and Pit cells) and in individual hepatocytes. The Bad expression area in the liver of LIFP mice increased 4 times against a background of the unchanged Bcl-2 expression area. Changes in the brightness (a parameter inversely proportional to the marker concentration) of Bad and Bcl-2 areas did not reach significance. Our results indicate a weakening of the antiapoptotic protection of liver cells of LIFP animals, which creates conditions for activation of the “mitochondrial branch” of apoptosis. Melatonin treatment of LIFP mice resulted in a 3.3-fold increase in Bcl-2 expression area and a 2.7 % decrease in Bcl-2 region brightness compared with the experimental untreated group. Bad protein parameters were unreliable. Thus, melatonin treatment of animals cancels the effect of LIFP, restoring the Bcl-2 expression area and increasing this protein concentration, which indicates an increase in antiapoptotic protection and creates conditions for blocking the development of the “mitochondrial branch” of apoptosis in liver cells

Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide

Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76)

评估行业间劳动力资源流动对俄罗斯经济中总劳动生产率的作用

Received January 23, 2022; accepted March 18, 2022.Дата поступления 23 января 2022 г.; дата принятия к печати 18 марта 2022 г.Relevance. Economic growth can be achieved in two different ways: through technological improvements and reallocation of market shares from less to more productive units. Despite the significant research literature on innovation in Russia, the literature on market selection, especially at the sectoral level, is relatively scarce. This is the research gap that this study aims to address. Research objective. The article assesses how labor resource reallocation between sectors has influenced the dynamics of aggregate labor productivity in the Russian economy over the past two decades. Data and methods. For this purpose, the growth of aggregate labor productivity was decomposed into the growth of productivity within the sectors themselves and the reallocation of labor resources between them. This allowed us to conduct a quantitative estimation of the role of market selection at the sectoral level. For our study, we used data from Rosstat (from 2002 to 2018) and the World Input- Output Database (from 2000 to 2014). Results. For Rosstat data, the ratio of the effect of changes in labor productivity and labor resource reallocation by sector on total labor productivity over the period was 0.71/0.29, and for WIOD data it was 0.44/0.56. This indicates that labor resources are more likely to be reallocated to related sectors (e.g. between manufacturing industries). Conclusions. The results suggest that there is competitive market selection at the sectoral level and that labor has generally been reallocated to more productive sectors of the economy, contributing significantly to the growth of aggregate productivity in the economy. Our study shows the sectors of the economy where this reallocation has taken place, which may help to determine where this process is successful and where it needs additional stimulation.Актуальность. Экономический рост может быть достигнут двумя различными способами: за счет технологических усовершенствований и перераспределения доли рынка от менее производительных единиц к более производительным. Несмотря на значительный объем исследовательской литературы по инновациям в России, литература по выбору рынка, особенно на отраслевом уровне, относительно скудна. На устранение данного пробела и направлено данное исследование. Цель исследования. В статье оценивается как переток трудовых ресурсов между секторами влиял на динамику совокупной производительности труда в российской экономике за последние два десятилетия. Данные и методы. С этой целью была осуществлена декомпозиция роста совокупной производительности труда на рост производительности внутри самих секторов и переток трудовых ресурсов между ними. Для проведения исследования нами были использованы данные Росстата (с 2002 по 2018 год) и Всемирной базы данных «затраты-выпуск» (с 2000 по 2014 год). Результаты. По данным Росстата соотношение влияния изменений производительности труда и перетока трудовых ресурсов по секторам на совокупную производительность труда за указанный период составило 0,71/0,29, а для данных WIOD – 0,44/0,56. Это указывает на то что трудовые ресурсы более склонны перераспределяться в смежные сектора (например, между отраслями обрабатывающего производства). Выводы. Полученные результаты свидетельствуют о наличии конкурентного отбора на уровне секторов экономики, а также о том, что трудовые ресурсы в целом перераспределялись в более производительные отрасли экономики внося весомый вклад в рост совокупной производительности труда в экономике. Наше исследование оценивает в какие именно сектора экономики это перераспределение происходило, что может помочь определить, где данный процесс успешен, а где этот процесс нуждается в стимулировании.现实性：经济增长可以通过两种不同的方式实现：技术改进；将市场份 额从生产力较低的单位转移到生产力更高的单位。尽管俄罗斯有大量关 于创新的研究，但关于市场选择，尤其是在行业层面的学术研究相对稀 缺。本研究旨在填补这一空白。 研究目标：本文评估了在过去的20年里，行业间劳动力资源的流动是如 何动态影响俄罗斯经济中总劳动生产率的。 数据和方法：因此，总劳动生产率的增长被分解为各行业内部的生产率 增长和行业之间的劳动力资源流动。为了进行这项研究，我们使用了来 自俄罗斯联邦国家统计局（2002年至2018年）和世界投入产出数据库 （2000年至2014年）的数据。 研究结果：根据俄罗斯联邦国家统计局的数据，在此期间，各行业的劳 动生产率和劳动力资源流动对总劳动生产率的影响比率为0.71/0.29，而 世界投入产出数据库比率为0,44/0,56。这表明劳动力资源更有可能重新 分配到相似行业（例如，制造业之间）。结论：结果显示，在行业层面存在竞争性选择，劳动力通常流动到更有 生产力的部门，这大大促进了经济总生产力的增长。我们的研究准确评 估了这种劳动力流动发生在哪些经济部门。这有助于确定这一过程在哪 些方面是成功的，以及在哪些方面需要优化。This research was supported by grant No. 19-18-00262, “Modeling of Balanced Technological and Socio-Economic Development of Russian Regions», from the Russian Science Foundation.Исследование выполнено при поддержке гранта РНФ (проект №19–18–00262 «Моделирование сбалансированного технологического и социально-экономического развития российских регионов»)

STUDYING THE POSSIBLE MUTAGENIC PROPERTIES OF NEW MEDICINE ON THE BASIS OF COMPLEX LITHIUM CITRATE, ALUMINUM OXIDE AND POLYMETHILSILOXANE

Aim of the study was to investigate the possible mutagenic properties of a new drug based on a lithium-containing substance – a complex of lithium citrate, polymethylsiloxane and aluminum oxide. Material and methods. Methods for testing mutagenicity using chromosomal aberrations in the bone marrow cells of CBA mice and somatic recombination in Drosophila melanogaster were used. Results. It was shown that a single intragastric administration of drug at a dose of 5000 mg/kg and a fivefold course of administration at a dose of 400 mg/kg to CBA mice did not increase the level of cytogenetic disorders in bone marrow cells. The study of the lithium complex drug in a somatic mosaicism test revealed that the preparation at a dose of 2000 mg/kg does not increase the frequency of mutations in Drosophila melanogaster. Conclusion. A single intragastric administration of the studied drug at a dose of 5000 mg/kg and its course administration (400 mg/kg × 5) do not increase the level of cytogenetic disorders in the bone marrow cells of CBA mice. In the somatic recombination (mosaicism) test system on D. melanogaster, no increase in the appearance of mutant setae and spots on the body and head was observed when using yellow and singed markers. The results of the study indicate that the studied drug does not have mutagenic properties

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3