Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO.

Guanidine Derivatives of Quinazoline-2,4(1,3)-Dione as NHE-1 Inhibitors and Anti-Inflammatory Agents.

Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1,3)-diones and quinazoline-4(3)-one guanidine derivatives. In the present work, novel N1,N3-bis-substituted quinazoline-2,4(1,3)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled.

Discovery of Nitro-azolo[1,5-]pyrimidines with Anti-Inflammatory and Protective Activity against LPS-Induced Acute Lung Injury.

Acute lung injury remains a challenging clinical condition, necessitating the development of novel, safe and efficient treatments. The prevention of macrophage M1-polarization is a viable venue to tackle excessive inflammation. We performed a phenotypic screening campaign to identify azolopyrimidine compounds that effectively inhibit LPS-induced NO synthesis and interleukin 6 (IL-6) secretion.

Fundamentals for forage crop breeding and seed production in Russia.

Plant breeding and seed production of new generation fodder crops is the groundwork for creating a fodder base for livestock production in sufficient quantities. The Federal Williams Research Center of Forage Production and Agroecology founded in 2018 based on of the All-Russia Williams Fodder Research Institute and other scientific institutions is the largest and most comprehensive center in the field of food production. It develops new techniques and methods for creating initial seed material based on a wide use of genetics, biotechnology, microbiology, immunology, ecology, biogeocenology, and cell selection.

Azolo[1,5-]pyrimidines and Their Condensed Analogs with Anticoagulant Activity.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents.

Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors.

The Na/H exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range.

[Development and evaluation of simulation methods for manual skills training in 'Removable dentures' module].

Unlabelled: To determine the effectiveness of a simulation method of teaching manual skills modulo 'removable dentures' in a clinical setting.

Material And Methods: The material 1 phase of the study were 82 people, students of 3 courses, divided into a control group where the training was conducted with the use of standard phantoms and group study which used a dental simulator CDS 100 of V generation. Material 2 stages presented 48 people who participated in phase 1 and divided into groups similar to the 1 stage, young professionals in 2016.

[The Medical Social Characteristics of Women with Oncologic Diseases].

The oncologic pathology is covered by the group of socially significant diseases and ranks second position in the structure of population mortality in the Russian Federation, being one of the actual medical social problems of modern society. In the Russian Federation and all over the world, over last years, a steady rise of morbidity of malignant neoplasms is observed. At that, it is more intensive among female population.

Effect of GRP119 Receptor Agonist, Compound MBX-2982, on Activity of Human Glucokinase.

Validation of the method for studies of glucokinase activators by the spectrophotometric method in an in vitro test system is carried out. The advantage of NAD coenzyme vs. thio-NAD is proven.

[The development of prevention of alcoholic addiction on the basis of analysis of medical social risk factors and prognostic modeling].

The alcohol addiction is one of most actual medical social problems of modern society. The medical biological and social hygienic risk factors play significant role in its development. As a result of that, actual priority is attached to development of methodology and implementation of screening program with the purpose of analyzing medical social characteristics of examined contingent, forming of risk groups and administrating of adequate preventive curative preventive measures.

[The impact of socio-economic factors and lifestyle on the health of the population in the Voronezh region].

There are presented results of research of the impact of socio-economic factors, environmental factors and lifestyle on the health of the population. Among the socio-economic indices there are analyzed: the health expenditure; per capita income; living wage; the cost of the minimum food basket; the percentage ofpersons with income below the subsistence minimum; the amount of living space per person; the percentage of apartments that do not have running water; the percentage of apartments that do not have sewage systems; the proportion of living space, equipped with central heating; housing area per overall per capita at the end of the year. Also there are considered negative lifestyle factors: the abuse of alcohol and tobacco.

Effect of Pyrrolobenzimidazole Derivative RU-792 on Experimental Brain Ischemia.

Compound RU-792 showed pronounced anti-ischemic activity and improved survival of rats with brain ischemia by normalizing parameters of spontaneous motor activity and reducing neurological deficit within 3 post-operative days being superior to the reference drug mexidol by this parameter. RU-792 inhibited the formation of conjugated dienes and malonic dialdehyde and increased activity of the antioxidant enzyme glutathione peroxidase thereby modulating the parameters of free radical oxidation in rats subjected to ischemia more effectively than mexidol.

Experimental study of the effect of a new antioxidant agent on learning and memory.

This work presents the results of studying the effect of a new antioxidant compound enoxyphol on learning and memory in rats.

Antithrombogenic activity of antioxidant compounds.

Antithrombotic activities of enoxifol, a new antioxidant with antiaggregant activity demonstrated in vitro and in vivo, and antioxidant mexidol were compared on the rat model of arterial thrombosis induced by application of 50% ferric chloride. Acetylsalicylic acid (antiaggregant) served as the reference drug. All drugs exhibited dose-dependent antithrombotic activity.

Antioxidant properties of pyrrolobenzimidazole derivative RU-792: experimental study.

We studied antioxidant activity of new derivative of pyrrolo[1,2-α]benzimidazole RU-792 and compared its effects on free radical processes with those of the reference antioxidant Trolox in four model free-radical systems. RU-792 had high antioxidant activity determined by its intrinsic antiradical properties. RU-792 was superior to Trolox by antioxidant activity in the models of Fe(2+)-induced chemiluminescence of lipids with 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid), but less effective in the model of luminol-dependent chemiluminescence.

[Antioxidants: current situation and perspectives].

In the overview one can find analysis medico-biological aspects of free radical theory, clinical experience of antioxidants using, perspectives of new active agents and possible directions of theirs practical use.

[Comparative characteristics of antioxidant properties of hypoglycemic agents diabenol and gliclazide].

The antioxidant properties of diabenol and gliclazide with reference to mexidol have been studied in vitro on several model systems, including chemiluminescence (CL) of lipids, CL with generation of reactive oxygen species (ROS), CL dependent on luminol oxidation by peroxy radicals, and the Glavind DPPH free-radical method. Diabenol exhibited the properties of a scavenger of superoxide anions and hydroxy and peroxy radicals in model CL systems with ROS generation. The activity of diabenol in inactivating ROS was about 8 times higher compared to mexidol.

[The issues of population reproductive health in Voronezhskaya oblast and means of its improvement].

The article deals with the results of analysis of demographic indicators of natural migration of population in Voronezhskaya oblast in 1999-2008 revealing particular characteristics. The state of reproductive health of population in oblast is characterized by stable preservation of lower level of birth rate, higher indicators of total mortality and negative natural growth of population. The allotment of "maternal capital" at the birth of second child from 2006 and increase of one-time dowry at child birth in the Voronezh region ceased the birth-rate falling and mapped out a growth trend.

[The medical social risk factors of developing the iron-deficiency anemia in pregnant women].

The results of study of medical social risk factors of developing the iron-deficiency anemia in pregnant women are presented. The medical case history data, the characteristics of pregnancy, delivery and puerperal period course, the indicators of laboratory and instrumental findings are discussed in their dynamics. The analysis of significance of risk factors is carried out, the results of comparing of parameters of basic and control groups according Student's test were used.

[Antioxidant and membranoprotective properties of trolox].

The antioxidant and membranoprotective properties of trolox have been studied in vitro. It is established that trolox possesses antioxidant properties, inhibiting ascorbate-dependent lipid peroxidation of liver homogenates and Fe(2+)-induced lipid chemiluminescence of egg-yolk lipids. In addition, trolox exhibits a broad spectrum of antiradical activity and interacts with stable free 2,2-diphenyl-1-picrylhydrazyl radical so as to reduce the generation of luminol radicals and reactive oxygen species and to bind peroxy radicals.

[Modelling of intrauterine hypoxia].

An experimental model of chronic intrauterine hypoxia is proposed. This model reflects the most typical posthypoxic impairments for the above pathology: intrauterine growth retardation, alterations in the placental parameters, posterity death in the neonatal period, physical retardation, postnatal disorders in the CNS functions.

[Study of antiradical activity of new compounds by chemiluminescence].

Antioxidative and antiradical properties of a new antioxidant cerebroprotective drug, enoxifol (benzimidasole derivative), were compared with mexidol by means of three chemiluminescent techniques: luminol autooxidation system, Fe2+-induced lipid chemiluminescence and lucigenin-induced chemiluminescence with superoxide generation by xanthine-xanthine oxidase system. Enoxifol exhibited higher antiradical activity than mexidol. This was shown by suppression of luminol radicals and superoxide anion-radical generation.

[Anti-ischemic properties of the novel antioxidant enoxifol].

The antiischemic properties of the new antioxidant drug enoxifol, representing a derivative of N9-imidazo[1,2-a]benzimidazole, was studied in rats on the models of a double-vessel occlusion of common carotid arteries under normal conditions and on the background of irradiation. In addition, we studied the effect of enoxifol on the rehabilitation of experimental animals in the early reperfusion period after total brain ischemia.