Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2,4]triazino[2,3-c]quinazolines.

Designing novel biologically active compounds with anti-inflammatory properties based on condensed quinazolines is a significant area of interest in modern medicinal chemistry. In the present study, we describe the development of promising new bioactive molecules through the bioisosteric replacement of a carbon atom with a sulfur atom in anti-inflammatory agents, specifically 3-methyl-2-oxo-2-[1,2,4]triazino[2,3-]quinazolin-6-yl)butanoate. Design and synthetic studies have led to the series of previously unknown substituted 2-[((3-R-2-oxo-2-[1,2,4]triazino[2,3-]quinazolin-6-yl)methyl)thio]carboxylic acids and their esters.

Development and Optimization of Nasal Composition of a Neuroprotective Agent for Use in Neonatology after Prenatal Hypoxia.

The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system (CNS), bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. The creation of new dosage forms for neonatology using mathematical technologies and special software in pharmaceutical development allows for the creation of cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research.

Optimization of the Search for Neuroprotectors among Bioflavonoids.

For the first time, to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies; these include docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin as well as a program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules-quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, and Catechin-3-gallate-according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.

Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection.

Despite the significant progress in the fields of biology, physiology, molecular medicine, and pharmacology; the designation of the properties of nitrogen monoxide in the regulation of life-supporting functions of the organism; and numerous works devoted to this molecule, there are still many open questions in this field. It is widely accepted that nitric oxide (NO) is a unique molecule that, despite its extremely simple structure, has a wide range of functions in the body, including the cardiovascular system, the central nervous system (CNS), reproduction, the endocrine system, respiration, digestion, etc. Here, we systematize the properties of NO, contributing in conditions of physiological norms, as well as in various pathological processes, to the mechanisms of cytoprotection and cytodestruction.

Combined Pharmacological Modulation of Translational and Transcriptional Activity Signaling Pathways as a Promising Therapeutic Approach in Children with Myocardial Changes.

Myocardial hypertrophy is the most common condition that accompanies heart development in children. Transcriptional gene expression regulating pathways play a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy, and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels.

Altered Blood Molecular Markers of Cardiovascular Function in Rats after Intrauterine Hypoxia and Drug Therapy.

Many children and adults who have suffered prenatal hypoxia at an early age develop many serious diseases. This disease is an actual problem of pediatric cardiology and little studied. The aim was to analyze the cardioprotective effect of L-arginine, Thiotriazoline, Angioline, and Mildronate on the cardiovascular system of rats after prenatal hypoxia.

Cardioprotective Activity of Pharmacological Agents Affecting NO Production and Bioavailability in the Early Postnatal Period after Intrauterine Hypoxia in Rats.

Intrauterine hypoxia in newborns leads to a multifaceted array of alterations that exert a detrimental impact on the cardiovascular system. The aim of this research was to assess the cardioprotective effects of modulators of the nitric oxide (NO) system, including L-arginine, Thiotriazoline, Angiolin, and Mildronate, during the early postnatal period following intrauterine hypoxia. Methods: The study involved 50 female white rats.

Association of Myocardial Changes and Gene Expression of the and -Calcineurin Signaling Pathway in Children with Bicuspid Aortic Valve.

Background: The role of NFATC gene expression in bicuspid aortic valve (BAV) progression is not fully understood. The aim of this study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV.

Methods: In 47 children with BAV, the standard Doppler echocardiographic characteristics were detected, and the expression of the NFATC1 and NFATC4 genes was studied.

ULTRASTRUCTURAL FEATURES OF THE REARRANGEMENT OF THE CELLS OF THE HEMATOTESTICULAR BARRIER AND THE SPERMATOGENIC EPITHELIUM OF THE RATS TESTICLES DURING THE SUDDEN WITHDRAWAL OF PREDNISOLONE AFTER ITS LONG-TERM INTRODUCTION IN HIGH DOSES.

With long-term use of hormonal drugs, according to the principle of "negative feedback", the production of own hormones by the endocrine glands is inhibited. With sudden withdrawal, in particular, of glucocorticoids, there are processes that threaten the development of secondary adrenal insufficiency. The purpose of the study: to establish the peculiarities of the reconstruction of the cellular elements of the testicles of white rats after the withdrawal of high doses of prednisolone.

ULTRASTRUCTURAL FEATURES OF THE REARRANGEMENT OF CELLS OF THE HEMATOTESTICULAR BARRIER AND SPERMATOGENIC EPITHELIUM OF THE RATS TESTICLES AFTER INTRODUCTION OF HIGH DOSES OF PREDNISOLONE.

A feature of recent decades is the gradual increase in the level of male infertility, one of the important causes of which, of course, is endocrine dysfunction of various origins. Therefore, the aim of the study was to establish the features of the rearrangement of the testicle's cellular elements of white rats with the introduction of high doses of prednisolone. An ultrastructural study was carried out on 42 male rats.

COMPARATIVE ANALYSIS OF ENDURANCE CEMENTS FOR THE FIXATION OF NON-REMOVABLE ORTHOPEDIC CONSTRUCTIONS UNDER THE ACTION OF CYCLIC COMPRESSION.

Objective: The aim: To conduct studies of the physical and mechanical properties of cements for fixation, namely the duration of cement samples under cyclic compression.

Patients And Methods: Materials and methods: We have conducted a study of 6 cements for permanent fixation of fixed structures of dentures. To study the duration of cements under cyclic compression, a special stand was used, which allows testing samples for cyclic compression with a load frequency of 5.

CYTOKINOGENESIS DISORDERS IN MECHANISMS OF THE EXPERIMENTAL PERODONTITIS DEVELOPMENT AND THEIR CORRECTION BY FLAVONOL.

Objective: The aim: Evaluation of changes in proinflammatory and anti-inflammatory units of the cytokine profile in the mechanisms of development of experimental bacterial-immune periodontitis and elucidation of the effect of flavonol quercetin on its parameters.

Patients And Methods: Materials and methods: Experimental periodontitis was caused by introducing into the tissues of the periodontal complex a mixture of microorganisms diluted with egg protein. In order to enhance the immune response, a complete Freund's adjuvant was injected into the rat's paw at the same time.

Social and Psychiatric Aspects of the Emigration Problem in Ukraine.

The article presents data on a new scheme of complex treatment and rehabilitation of emigrants with psychogenic, endogenous and organic depressive disorders, as well as the results of comparative analysis of the effectiveness of this scheme, compared to the traditional one. The use of the proposed treatment scheme also allowed to reduce the severity of anxiety, indicators of the severity of psychopathological symptoms, improve the quality of life among emigrants suffering from depressive disorders of different genesis. The received results allow us to recommend the scheme we have developed for implementation in the complex treatment of emigrants suffering from depressive disorders of psychogenic, endogenous, and organic genesis.

Risk of eating disorders in university students: an international study in Hungary, Poland and Ukraine.

Objective: In this international study, the prevalence of Eating disorders (EDs) was determined among university students and identified associated demographic and behavioral factors predicting disorders using data from three European countries.

Methods: The survey was conducted in Hungary, Poland, and Ukraine in 2018. Registered full-time students completed an online anonymous questionnaire.

Determining the frequency of functional disorders of the TMJ in patients with mandible fractures depending on the location.

Objective: The aim: To investigate the frequency of functional TMJ disorders in patients with fractures of the mandible.

Patients And Methods: Materials and methods: To achieve this goal, 111 patients hospitalized in the department of surgical dentistry of the Chernivtsi Regional Clinical Hospital were examined for traumatic fractures of the mandible with functional disorders of the TMJ (occlusive, muscular, articular disorders). The examination of patients with functional disorders wasbased on Express - the conclusion of the Hamburg Protocol: 1.

Heart reaction of male and female with streptozotocin induced diabetes on cholinergic impacts.

Objective: The aim: Find out the nature of the changes sensitivity of the heart to the cholinergic influences the development of diabetes depending on gender.

Patients And Methods: Materials and methods: In experiments on adult male and female rats, type 1 diabetes by momentary introduction of streptozotocin at a dose of 60 mg/ kg into the peritoneal cavity was modeled. Animals were examined after 15, 30, 60 and 90 days after introduction of streptozotocin.

The effect of two formulations of carbon enterosorbents on oxidative stress indexes and molecular conformation of serum albumin in experimental animals exposed to CCl.

The liver failure means inability to perform its normal synthetic, biotransformation and excretory functions. The disturbance of metabolic processes leads to the development of "metabolic endogenous intoxication" resulting in oxidative stress. Oxidative stress initiates the processes of oxidation of amino acid residues of blood plasma proteins causing the changes in their structure and functions.

Clinical efficacy of therapeutic keratoplasty using corneal xenografts in patients with corneal ulcers.

to assess the clinical efficacy of keratoplasty using a corneal xenograft in patients with corneal ulcers of various etiologies. A total of 46 patients (49 eyes) with complicated corneal ulcers (perforated or with impending perforation) have been operated. Freeze-dried corneal xenografts have been used for keratoplasty.

Biochemical responses of freshwater mussel Unio tumidus to titanium oxide nanoparticles, Bisphenol A, and their combination.

Multiple interactions between different pollutants in the surface waters can cause unpredictable consequences. The aim of the study was to evaluate the combined effect of two widespread xenobiotics, titanium oxide nanoparticles (TiO) and bisphenol A (BPA), on freshwater bivalve Unio tumidus. The specimens were exposed for 14 days to TiCl (Ti, 1.

Hepatoprotective Effect of Melatonin in Toxic Liver Injury in Rats.

toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis.

[Problem of mineral insufficiency at chronic pancreatitis in dependence on age].

The high incidence of chronic pancreatitis (CP) which arise at young people of working age, the development of serious complications are pushing for the development of new diagnostic methods and the search for effective ways to treat this disease. In this regard, a relevant and promising direction is the further study of the mechanisms of pathogenesis and the formation of trophological (including mineral) deficiency in CP, followed by the development of comprehensive programs for their correction. is to study mineral status of patients with chronic pancreatitis, depending on their age.

High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine.

Sexually transmitted infections (STIs) remain major public health problems globally. Appropriate laboratory diagnosis of STIs is rare in Ukraine. We investigated the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) using the US FDA-approved Aptima Combo 2 and Aptima TV assays and compared the results with the conventional routine diagnostic tests (CDTs) in Ukraine.

[ACUTE SMALL BOWEL OBSTRUCTION. SOME ASPECTS OF CONSERVATIVE TREATMENT].

One of the complex problems in urgent abdominal surgery is acute small bowel obstruction (ASBO). The goal of our research is to improve treatment results for patients with ASBO by optimizing their diagnostic and therapeutic algorithm taking into account changes in the small intestine during its obstruction. We made a complex examination of 56 patients with ASBO who recovered after conservative therapy.