Pharmacological Correction Research Articles

Zebrafish as a Promising Model in Translational Neurobiology and Biomedicine

Abstract—High prevalence of the central nervous system disorders necessitates novel methods and approaches for their pharmacological correction. Traditionally used rodent models are limited by high costs of research, complex maintenance and care, and long development. The use of alternative, aquatic model organisms, such as the zebrafish (Danio rerio), in translational neuroscience and medicine allows for fast efficient experimentation with easy maintenance, manipulations, and rapid development. Zebrafish are also sensitive to major classes of physiologically active agents, which makes this model indispensable for preclinical studies of a wide range of small molecules. The similarity of neurochemical systems, the presence of major neurotransmitters, a high degree of genetic and physiological homology with humans, the availability of both larval and adult fish models, and embryonic transparency provide multiple possibilities for using this organism to model CNS pathologies and its genetic and environmental causes.

SALIFEN PREVENTS PERINATAL HYPOXIA-INDUCED COGNITIVE IMPAIRMENTS AND CHANGES IN GABA<sub>B</sub> RECEPTOR EXPRESSION IN THE RAT NEOCORTEX

We have studied the effects of acute normobaric hypoxia in the early postnatal period of the development (the 2nd postnatal day) on learning and memory abilities and the expression of GABAB receptors in the neocortex (medial prefrontal cortex) in adolescent rats (the 55–60th postnatal day), as well as the possibility of correction of the revealed impairments by GABA derivative salifen. It was shown that perinatal hypoxia disrupts task acquisition and consolidation in the novel object recognition test, impairs passive avoidance performance, and also reduces spatial learning abilities in the Morris water maze. Western blotting analysis revealed increased levels of GABAB receptor protein in the medial prefrontal cortex of the rats following the exposure to perinatal hypoxia. Post-hypoxic daily salifen injections over 14 days at a dose of 15 mg/kg improved cognitive abilities in rats, and also normalized GABAB receptor content in the rat medial prefrontal cortex. The results of the present research are of considerable significance for solution of applied problem of neonatology – the search for effective drug candidates for the pharmacological correction of the impacts of perinatal hypoxia.

Оцінка споживання стимуляторiв фізичної та розумової працездатності для лікування астенiчного синдрому методом анкетування фармацевтичних працiвникiв

Asthenia or asthenic syndrome (AS) is a condition in which a person is characterized by excessive fatigue, marked weakness, mood swings and mainly negative mood. Asthenia is a symptom of many organic and mental diseases. A person usually cannot engage in both physical and mental work for a long time due to prolonged or chronic fatigue. AS can be considered as a universal protective mechanism that accompanies various psychophysiological processes and somatic diseases, which are based on mechanisms of energy deficiency. Being in its essence a protective mechanism that signals the exhaustion of energy resources, AS can become a pathological, extremely disabling condition and even transform into its own nosology - chronic fatigue syndrome, an immune-mediated disease. Therefore, AS is a medical and social problem and requires adequate pharmacological correction. Today, drugs such as: adaptogens of plant and animal origin are used for the treatment of AS and stimulation of physical and mental performance; actoprotectors, antihypoxants; drugs with metabolic and neurotropic effects, B vitamins. The purpose of the work. Assessment of consumption and availability in the pharmaceutical market of Ukraine and analysis of the range of drugs for stimulation of physical and mental performance in the treatment of AS when dispensing over-the-counter drugs for the symptomatic treatment of asthenia. Research methods. Sociological, system-analytical, analytical. Results. A study was conducted to assess consumption and availability on the pharmaceutical market of Ukraine and to analyze the assortment of pharmaceutical products for the dispensing of over-the-counter drugs for the symptomatic treatment of asthenia.

Quantitative characteristics of structural changes in the myocardium of white rats during the modeling of adrenaline myocardiodystrophy and its pharmacological correction

Pathology of the cardiovascular system is one of the leading causes of mortality and disability. In anesthesiology practice, it is the most common comorbid condition that leads to perioperative complications and fatal outcomes. The aim of the study was to substantiate the cardioprotective properties of succinic acid, sodium oxybutyrate, and quercetin based on the study of the myocardial morphological structure in the correction of experimental cardiac pathology. The experiments were conducted on white rats, in which adrenaline-induced myocardial dystrophy was modeled. The correction was performed using succinic acid, sodium oxybutyrate, and quercetin. Morphological studies were conducted at 2 and 24 hours after correction. At 2 hours after adrenaline administration, pronounced venous and arterial congestion was observed in the myocardium. The lumen of vessels appeared dilated, and their walls appeared thinner. In animals that received corrective agents after adrenaline, a positive effect of their application was noted. Vascular congestion was significantly reduced. The arterial walls had normal thickness, and the internal elastic membranes were moderately tortuous. No significant changes were observed in cardiomyocytes. At 24 hours from the start of pathology modeling and its pharmacological correction, the changes in the myocardium of the animals were much more pronounced compared to those with a 2-hour exposure, although in animals treated with corrective agents, the changes were less pronounced than in untreated animals. Rats exposed only to adrenaline showed significant trophic disturbances in cardiomyocytes, which developed against the background of coronary circulation disorders, manifested as wall thickening and narrowing of arterial lumens. The veins were congested, and blood extravasation was observed in the interstitium. Perivascular spaces expanded due to edema. Cardiomyocytes exhibited dystrophic changes, including areas with clarified cytoplasm, often with its homogenization and karyolysis. Histological data were morphometrically confirmed by changes in the Wogenworth index and nuclear-cytoplasmic ratios. The obtained results indicate the positive effect of the used corrective agents. Quercetin demonstrated slightly higher efficacy in this regard.

Оценка эффективности нового препарата Экспресс Успокоин® таблетки при ситуационной коррекции поведенческих проблем у кошек

The totality of the results presented in this paper allows us to conclude that it is expedient to use Express Uspokoyin® tablets for the pharmacological correction of a wide range of behavioral abnormalities in cats that occur in various stressful situations.

Features of using prolonged-release melatonin in patients with type 2 diabetes

Diabetes mellitus (DM) and its complications are one of the leading causes of death worldwide, with approximately 700 million people expected to suffer from DM by 2045, according to the International Diabetes Federation. DM is a progressive, chronic disease that affects various body systems and can lead to serious physical health complications. Type 2 diabetes mellitus (T2DM) has been shown to be associated with a higher incidence of sleep disturbances, which may be due to the disease itself or secondary complications or comorbidities associated with DM. However, epidemiological evidence suggests a higher risk of obesity, metabolic syndrome, and T2DM in individuals with shorter sleep duration and poor quality of sleep. Therefore, an assessment of the quality of sleep, its disorders and their pharmacological correction is recommended as a comprehensive medical examination for existing T2DM and for groups at risk of its development. Among pharmacotherapeutic agents for the treatment of sleep disorders, melatonin (N-acetyl-5-methoxytryptamine) attracts special attention. It is indoleamine, a pineal hormone synthesized in the human body, which name is related to the ability to aggregate melanin pigment granules. It has been found that melatonin directly participates in many biological processes and limits oxidative stress both extracellularly and intracellularly. Endogenous melatonin has linear kinetics, the half-life of the usual form of melatonin with rapid release ranges from 45 to 65 minutes, it is quickly metabolized and is completely excreted after 3–4 hours. Currently, 1 and 2 mg prolonged-release forms of melatonin are available, which provide slower and longer absorption, a delayed and lower peak dose, and levels maintained for 8 to 10 hours— similar to the physiological secretion curve of endogenous melatonin. Since the dose of melatonin in prolonged-release forms is much lower than in immediate release forms, this will help reduce the risk of possible side effects, including in patients with T2DM and in groups at risk of its development.

Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity.

The crystal structure and the biological activity of a new coordination compound of magnesium ions with comenic acid, magnesium comenate, was characterized and studied. Quantitative and qualitative analysis of the compound was investigated in detail using elemental X-ray fluorescent analysis, thermal analysis, IR-Fourier spectrometry, UV spectroscopy, NMR spectroscopy, and X-ray diffraction analysis. Based on experimental analytical data, the empirical formula of magnesium comenate [Mg(HCom)2(H2O)6]·2H2O was established. This complex compound crystallizes with eight water molecules, six of which are the hydration shell of the Mg2+ cation, and two more molecules bind the [Mg(H2O)6]2+ aquacation with ionized ligand molecules by intermolecular hydrogen bonds. The packing of molecules in the crystal lattice is stabilized by a branched system of hydrogen bonds with the participation of solvate water molecules and oxygen atoms of various functional groups of ionized ligand molecules. With regard to the biological activity of magnesium comenate, a neuroprotective, stress-protective, and antioxidant effect was established in in vitro and in vivo models. In in vitro experiments, magnesium comenate protected cerebellar neurons from the toxic effects of glutamate and contributed to the preservation of neurite growth parameters under oxidative stress caused by hydrogen peroxide. In animal studies, magnesium comenate had a stress-protective and antioxidant effect in models of immobilization-cold stress. Oral administration of magnesium comenate at a dose of 2 mg/kg of animal body weight for 3 days before stress exposure and for 3 days during the stress period led to a decrease in oxidative damage and normalization of the antioxidant system of brain tissues against the background of induced stress. The obtained results indicate the advisability of further studies of magnesium comenate as a compound potentially applicable in medicine for the pharmacological correction of conditions associated with oxidative and excitotoxic damage to nerve cells.

Cognitive function restoration in rats with chronic brain ischemia using Semax and hopantenic acid comprehensive administration

The relevance and importance of treating patients with ischemic brain lesions are indisputable. Chronic ischemic processes in the brain occur much more frequently than acute cerebral circulation disorders, leading to prolonged disability and being the main contributors to a significant number of strokes. Cognitive dysfunctions prevail in the dynamics of the post-ischemic period and are often the primary determinants of the severity of residual organic and subsequent functional impairments of the brain. The aim of the study is to investigate the effectiveness of separate and combined administration of Semax and hopantenic acid in the pharmacological correction of cognitive disorders in rats with experimental chronic brain ischemia. It has been established that rats with chronic brain ischemia exhibit cognitive impairments from the 1st day, manifested in worsened learning processes, short-term and long-term memory functioning in the context of conditioned active avoidance and conditioned feeding reflexes. It has been shown that separate and combined application of Semax and hopantenic acid contributes to the restoration of the learning process and improvement of mnestic functions in rats with chronic brain ischemia. The most pronounced nootropic effect in rats with chronic brain ischemia was registered under the conditions of combined administration of Semax and hopantenic acid, starting from the 3rd day of the study. Subsequently, in terms of anti-ischemic efficacy, the effect of Semax follows, which was realized starting from the 3rd day of the study. The least pronounced neuroprotective effect belongs to hopantenic acid, starting from the 7th day of the study. The author considers the obtained data as experimental groundwork for the feasibility of clinically testing the nootropic effects of the combined administration of Semax and hopantenic acid in cases of chronic brain ischemia. The comprehensive pharmacological correction of cognitive disorders in chronic brain ischemia is pathogenetically justified and aimed at activating sanogenetic mechanisms.

New possibilities of multimodal correction of disorders of central nervous system functions in elderly persons

NEW POSSIBILITIES OF MULTIMODAL CORRECTION OF DISORDERS OF CENTRAL NERVOUS SYSTEM FUNCTIONS IN ELDERLY PERSONS Victor V. Kuznetsov, Serhiy H. Burchynskyi, Kostiantyn O. Apykhtin D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine, 67 Vyshgorodska Str., Kyiv 04114, Ukraine Introduction. The increase in the share of elderly and senile people in the population adds urgency to the problems of various forms of cognitive dysfunction and closely related psycho-emotional disorders and disorders of cerebral circulation. Real success in solving these problems is possible only with the application of therapeutic effects at the earliest possible stage of the disease, as well as with the possibility of implementing a pharmacological prophylactic approach. At the root of the weakening of cognitive functions is a violation of the neurotransmitter balance in the brain. An effective way to prevent it is the use of nootropics. Nootropics affect the biosynthetic energy, neurotransmitter processes in the brain, the blood supply to the brain by exerting a protective effect on the vascular wall, inhibiting the thrombus formation reaction, normalizing blood viscosity, etc. The drug MemoProve is a unique combination of neurotropic peptone polypeptides (N-PEP-12), which is able to reproduce the effects of natural neurotrophic factors in the central nervous system (NGF), as well as improve cholinergic neuromediation by activating the main enzyme of acetylcholine biosynthesis – choline acetyltransferase. The aim is comprehensive analysis of the effect of a course of MemoProve on the psycho-emotional state, the structure of the state of bioelectrical activity of the brain, and the state of cerebral blood circulation in the elderly. Materials and Methods. A comprehensive clinical and instrumental examination of 20 elderly patients (average age 68.2 ± 3.2 years) with initial manifestations of dyscirculatory atherosclerotic encephalopathy was conducted. Before conducting an analysis of the effect of course (1 month) use of MemoProve on the functional state of the brain in elderly patients, an EEG study was conducted before and 24 hours after taking 2 tablets of the drug in order to determine the sensitivity of the brain to MemoProve. Results and conclusions. Three variants of the EEG reaction to MemoProve were identified. Common to these options is an increase in the total power of electrogenesis of the brain (by 15-25 %), an increase in the frequency of the -rhythm – the main, basic rhythm of the EEG. The type of influence of MemoProve on the power of slow rhythms (delta, theta) has features depending on the EEG variant. In elderly patients, MemoProve caused an increase in the linear systolic blood flow velocity in the two middle cerebral arteries, the vertebral arteries and the main artery. The results of a comprehensive analysis of the effect of course therapy of MemoProve indicate its positive effect on the functional state of the brain (in terms of emotional and cognitive indicators, bioelectrical activity of the brain, the state of cerebral hemodynamics) in elderly people and give grounds for recommending MemoProve for use in the system of geriatric pharmacological correction of emotional and cognitive processes. Keywords: cognitive dysfunction, neurotransmitter balance, nootropics, peptone polypeptides, MemoProve, EEG.

Neurodegenrative changes in retina of rats with chronic epileptic syndrome under conditions of treatment with niacin-oxy-ethylidene-phosphonate germanate (MIGU-4)

Background:Epilepsy is accompanied by neurodegenerative changes, particularly those in the retina. Elucidation of the mechanisms of retinal alterations in a model of epileptic syndrome may allow for the development of new approaches to pharmacological vision correction. Purpose: To assess the morphological characteristics of the retina, particularly treated with niacin oxy-ethylidene phosphonate germinate (MIGU-4), in the pentylenetetrazole (PTZ)-induced kindling model of chronic epileptic syndrome. Material and Methods: PTZ was administered in Wistar male rats intraperitoneally (i.p.) at a daily dose of 35.0 mg/kg for 21 days. Rats with fully-developed generalized seizures were treated with MIGU-4 ip at a daily dose of 5.0 mg/kg or 25.0 mg/kg for 28 days. Thereafter, the animals were euthanized, their globes were enucleated, and retinal sections were prepared and stained with hematoxylin and eosin for morphological examination. Results: Cell density in the retinal ganglion cell layer was 2.14 times lower, and in the inner nuclear layer and outer nuclear layer, 41.0% and 19.0%, respectively, lower for the rats with fully developed kindled seizures than for controls (р less 0.05) In the presence of treatment with MIGU-4 ip at a daily dose of 25.0 mg/kg, cell density in the retinal ganglion cell layer and in the inner nuclear layer was 38% and 30,5%, respectively, higher than for controls (р less 0,05). There was no significant difference in the cell density in the outer nuclear layer between rats treated with MIGU-4 ip at a daily dose of 5 mg/kg or 25,0 mg/kg and controls (р more 0.05). Conclusion: The PTZ-induced kindling model of chronic epileptic syndrome is accompanied by degenerative changes in the eye. A course of treatment with MIGU-4 causes neuroptotective effects in a model of PTZ-induced retinopathy.

Novel 1,4-Dihydropyridine Derivatives as Potential Agents with Analgesic Activity IN Orofacial Trigeminal Pain Test: Experimental Preclinical Randomized Trial

Background. In the majority of cases, contemporary pharmacological correction mainly focuses on the most effective analgesia. Therefore, the search for and research into new analgesic drugs are a priority in modern pharmacology.Objective — to establish the level of analgesic activity in eight novel heterocyclic compounds of 1,4-dihydropyridine derivatives synthesized in a classic test of orofacial trigeminal pain in animal experiments.Methods. An experimental preclinical randomized trial of the analgesic activity in 1,4-dihydropyridine derivatives was carried out. The experiment was conducted on 100 white male outbred rats in the laboratory of the Fundamental and Clinical Pharmacology Department, St. Luke Lugansk State Medical University, Lugansk People’s Republic. Novel 1,4-dihydropyridine derivatives were preliminarily investigated in a virtual biological screening by means of Swiss Target Prediction tool (Swiss Institute of Bioinformatics, Switzerland). The laboratory animals were divided into a control group (rats were exposed to acute pain syndrome by injecting 0.1 ml of 5% formalin solution into the vibrissae area without pharmacological correction), a comparison group (rats which received metamizole sodium (OOO Farmstandard) at a dose of 7 mg/kg 1.5 hour prior to acute pain syndrome modeling in the vibrissae area), and eight experimental groups (1.5 hours before formalin administration, novel 1,4-dihydropyridine derivatives under study at a dose of 5 mg/ kg were intragastrically injected). 10, 15 and 20 minutes after simulating acute pain, the number of scratching movements of the forelegs around orofacial region per minute was counted. Statistical processing of the results involved methods of mathematical statistics for quantitative variability and was carried out using Statistica 12.5 (IBM, USA).Results. Animals treated with 1,4-dihydropyridine derivatives d02-133 and d02-172 under the experimental conditions showed a significant (13–21 times) decrease in scratching movements frequency by the 10th minute of observation in comparison with the control group. By 15th minute, the analgesic activity of the cyanothioacetamide derivatives increased 14 and 11 times as compared to these indicators of the reference group. After 20 minutes, the analgesic activity of these compounds in terms of inhibiting nociceptive impulses, as compared to the control group, was also high, as the number of scratching movements in the vibrissae area in animals of these experimental groups was 8–9 times lower than in control group. The orofacial trigeminal pain test detected the most exhibited analgesic activity in novel cyanothioacetamide derivatives d02-139, d02-133, and d02-172, which appeared to be higher than that of metamizole sodium.Conclusion. It was found that novel original derivatives of 1,4-dihydropyridine showed a high degree of analgesic activity.

Pharmacological correction of hepatotoxicity induced by Kinmiks

Improper usage of pyrethroid pesticides, non-compliance with the rules of storage and transportation can lead to negative consequences (poisoning, allergic reactions, chronic disorders of body systems, death). In recent decades, the attention of scientists has been attracted by the problem of toxic damage to the liver by pesticides. Kinmiks is a pyrethroid insecticide, the active ingredient is beta-cypermethrin (50 g/l). Conducted complex experimental studies have shown that Kinmiks, when administered intragastrically to animals, provokes the development of pathological reactions and has a toxic effect on the liver. It was concluded that in the complex treatment of poisoning with pesticides containing β-cypermethrin, the dipyroxime and pyridoxine hydrochloride should be used. For early diagnosis of pesticide poisoning the indicators of bilirubin, albumin, ALT, alkaline phosphatase and the ratio of ALT to alkaline phosphatase can be used as markers.

«Молчаливый соперник»: фармакологическая коррекция патологии малых дыхательных путей при бронхиальной астме (фокус на циклесонид)

«Молчаливый соперник»: фармакологическая коррекция патологии малых дыхательных путей при бронхиальной астме (фокус на циклесонид)

Orthodontic correction in rodents and hare-like animals: principles and methods of treatment

The aim: Our particular interest in this study is not only the ability to extrapolate the experience of orthodontics of humane medicine for effective orthodontic correction in representatives of the animal world, but also the possibility of using teleroentgenometry and craniometry to study the skull of rodents and hare-like animals for the early preclinical diagnosis of dental disease.
 Materials and methods. The data of teleroentgenography (TRG), cranio- and gnatometry, biochemistry of connective tissue (GAG, GP, HST), fluoroscopy, densitometric parameters for early subclinical detection of dental disease in chinchillas (Chinchilla lanigera (n=20)), guinea pigs (Cavia porcellus (n=48)) and rabbits (Oryctolagus cuniculus(n=52)) are presented. All stages of the effective correction of mesial occlusion of incisors in rabbits (N=5) and dystropia of premolars in guinea pigs (N=5) are described. The camputation of efforts and points of their application that are necessary to move the tooth of the ellodont type is carried out. There are given the sequential stages of creating a dental imprint or 3D models, as well as the manufacture of fixed orthodontic structures, including an elastophore, orthodontic buttons with an Enlight Ormco fixation for incisors; and individual extraoral devices with expanding screws for premolars are presented.
 Results. Namely, among animals with dental disease, the following anatomical characteristics reliably took place. The basal angle of inclination of the base of the jaws to each other characterizing the vertical position of the jaws increased by 11 %; the body of the lower jaw shortened by 18 %; the height of the branches of the jaw increased by 17.5, and the mandibular angle, which is measured between the tangents to the lower edge of the lower jaw and the back surface of its branches, increased by 6 %. These data must be considered together with a reliable densitometric decrease in bone density and changes of biochemical components of the connective tissue in the blood serum. An analysis of bone strength of rabbits and guinea pigs is given in Tab. 2, which shows that the bone marrow of animals with dental history is statistically significantly different from the strength of animal bones without such among patients of rabbits and guinea pigs (p = 0.012 and p = 0.024, respectively). Thus, the method of program densitometry can be used to quantify the severity of metabolic disorders in the bone tissue to predict the further course of the reparative process, to appoint adequate pharmacological correction and to control the evaluation of therapeutic measures.
 Conclusions. The study of dental pathology of rodents and hare-like animals using densitometric, craniometric and biochemical methods allows detection of disorders in the early preclinical stage. And the extrapolation of the experience of humane orthodontics solves the issue of correcting the occlusion of these types of animals to restore the possibility of self-feeding

Muscle activity and emotional behavior changes in rats with chronic brain ischemia via comprehensive pathogenetic correction

Cerebrovascular pathology has evolved from a medical concern to a social issue, with the efficacy of secondary neuroprotection remaining a pertinent question. While some investigations have been conducted to elucidate the effectiveness of a comprehensively grounded pharmacological correction scheme under conditions of experimentaly induced chronic brain ischemia, further refinement is necessary to understand the behavioral effects of animals, dosages, routes of administration of pharmacological agents, and analysis of obtained data. The aim of this study was to assess the effectiveness of applying Semax and hopantenic acid in the comprehensive treatment of motor disorders and established neurological impairments in rats with experimentally induced chronic brain ischemia. We determined that rats with chronic brain ischemia exhibit muscular dysfunctions and experience pronounced disturbances in emotional behavior from the first day. It has been demonstrated that the separate and combined application of Semax and hopantenic acid contributes to the restoration of muscle activity, normalization of coordination, and emotional behavior in rats with chronic brain ischemia. The most significant neuroprotective effect in rats with chronic brain ischemia was observed with the combined administration of Semax and hopantenic acid, starting from the 3rd day of the trial. The subsequent in the series of anti-ischemic effectiveness is the impact of Semax from the 3rd day of the experiment. The least pronounced neuroprotective effect was exhibited by hopantenic acid, starting from the 5th day of the experiment. We consider these findings to be an experimental foundation supporting the feasibility of clinically testing the effects of combined Semax and hopantenic acid administration, capable of restoring functional disorders caused by chronic brain ischemia. In conclusion, the observed effectiveness of the developed pathogenetically justified complex for the correction of post-ischemic muscle dysfunction and disorders indicates the development of an anti-ischemic effect, as well as the fundamental possibility of improving the treatment for patients with chronic brain ischemia through clinical intranasal administration of Semax, either alone or in combination with hopantenic acid. However, for a more comprehensive understanding of the temporal and dose-dependent effects of this complex pathogenetic correction scheme on other disorders and dysfunctions related to chronic brain ischemia and to formulate final conclusions, it is essential to conduct separate series of experimental studies.

Cortisol Monitoring Devices toward Implementation for Clinically Relevant Biosensing In Vivo.

Cortisol is a steroid hormone that regulates energy metabolism, stress reactions, and immune response. Cortisol is produced in the kidneys' adrenal cortex. Its levels in the circulatory system are regulated by the neuroendocrine system with a negative feedback loop of the hypothalamic-pituitary-adrenal axis (HPA-axis) following circadian rhythm. Conditions associated with HPA-axis disruption cause deteriorative effects on human life quality in numerous ways. Psychiatric, cardiovascular, and metabolic disorders as well as a variety of inflammatory processes accompanying age-related, orphan, and many other conditions are associated with altered cortisol secretion rates and inadequate responses. Laboratory measurements of cortisol are well-developed and based mainly on the enzyme linked immunosorbent assay (ELISA). There is a great demand for a continuous real-time cortisol sensor that is yet to be developed. Recent advances in approaches that will eventually culminate in such sensors have been summarized in several reviews. This review compares different platforms for direct cortisol measurements in biological fluids. The ways to achieve continuous cortisol measurements are discussed. A cortisol monitoring device will be essential for personified pharmacological correction of the HPA-axis toward normal cortisol levels through a 24-h cycle.

Endothelial dysfunction in a general practitioner’s work

Endothelial dysfunction (ED) is a pathological condition that is impairment in the synthesis of endothelial factors and is a major component in the pathogenesis of many diseases, including those of a therapeutic profile. Many specialists now consider ED as a universal component in the development of cardiovascular and respiratory diseases. The paper contains information about the main functions of the endothelium and their impact on the organs and systems of the body, the state of microhemocirculation, and the entire internal environment. It also considers ED that affects vasomotor, hemostatic, adhesive, and angiogenic functions and the main markers of endothelial damage. The possibilities of preventive measures and pharmacological correction of ED are discussed.

Indicators of Bioelectrical Activity of the Rat Heart After Prenatal Hypoxia and Pharmacological Correction

Background. Posthypoxic cardiopathy is one of the risk factors for the development of cardiovascular pathology (rhythm disturbances, vascular dystonia, etc.) in subsequent age periods and requires the development of treatment approaches. Objective. to evaluate the cardioprotective effect of modulators of the NO system by the effect on the ECG of rats after intrauterine hypoxia. Methods. Modeling of prenatal hypoxia (PH) by daily intraperitoneal administration of sodium nitrite solution to pregnant female white rats weighing 220–240 g, aged 4.5 months, from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. The offspring were administered daily from the 1st to the 30th day of life – tiazotic acid (morpholinium 3-methyl-1,2,4-triazolyl-5-thioacetic acid), 50 mg/kg, angiolin ([S]-2,6-diaminohexane acid 3-methyl-1,2,4-triazolyl-5-thioacecate), 50 mg/kg, L-arginine, 200 mg/kg, meldonium (2-(2-carboxyethyl)-1,1,1-trimethylhydrazinium), 100 mg/kg. Аnd then after 2 months of life, an ECG was recorded using the ECG TUNNEL system (without anesthesia). Results. Postponed PG leads to a decrease in heart rate and significant dominance of parasympathetic innervation in regulation of electrical activity of the heart, which can be caused by sinus blockade and may be a reflection of parasympathetic regulation of the heart instead of sympathetic control of electrical activity in the norm. The effectiveness of drugs can be presented in descending order: angiolin > tiazotic acid > meldonium. Angiolin proved to be more effective than tiazotic acidin normalizing the electrical activity of the heart and restoring the neurogenic regulation of the automatism of the function of the sinus node. Сonclusions. The prospects of further study of modulators of the NO system with different mechanisms of action as means of cardioprotection of posthypoxic disorders of the cardiovascular system in newborns are experimentally substantiated.

Adverse reactions of high-osmolar and low-osmolar radiographic contrast media in clinical practice

Introduction . Adverse drug reactions (ADR) to administration of radiographic contrast media (RCM) are observed in 10–20 % of patients. Individual tolerability of drugs is affected by RCM properties (ionicity, osmolarity). Aim . Evaluation of ADR in patients during diagnostic studies using high- and low-osmolar RCM. Methods . Analysis of 52 reports of adverse reactions to RCM registered in medical organizations of Voronezh region in 2014–2021 was performed. Group 1 included 21 patients with ADR to high-osmolar RCM (sodium amidotrizoate, yoxitalamic acid), group 2–31 patients with ADR to low-osmolar drugs (yogexol, yopromide, yopamidol, yoversol). Results . Age of patients is 6–82 years, median 48.5 years, children — 8 persons (15.4 %), women — 31 patients (59.6 %), serious reactions — 28 (53.8 %). Since 2017 there has been an increase in the number of ADRs with constant frequency of serious reactions. In 2020–2021 ADRs to low-osmolar drugs were mainly registered. Life-threatening conditions (anaphylactic shock, arterial hypotension, arrhythmia) were observed in 70.2 % of group 2, in 28.6 % of group 1 (p=0.007). One patient with initial renal dysfunction and comorbid pathology was reported to develop nephrotoxicity to yogexol. Pharmacological correction was performed in 92.3 % of cases. In 57.7 % of the patients ADR ended in recovery, in the other cases — state improvement. Conclusion . Side effects of high-osmolar and low-osmolar RCM mainly had form of hyperergic reactions of immediate type and were reversible. High frequency of serious reactions to lowosmolar RCM against an increase in their use requires a more careful selection of patients for X-ray contrast studies.

Protective influence of the zinc complex of 1-butylvioluric acid on the development of the liver tissue culture in the presence of convulsive poisons

Introduction. Currently, the actual problem is the search for substances that can be used as drugs for the pharmacological correction of the effects of cytostatic damage by convulsive poisons. It is known that the liver is the first organ to encounter any foreign molecule carried by the portal bloodstream, and it is the most damaged. The aim of this work was to study the effect of the zinc complex of 1-butylvioluric acid on the development of an organotypic culture of rat liver tissue after poisoning with 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride. Material and methods. White 3-month-old male Wistar rats were used in the experiment. To study the effects of the test substances, liver tissue was selected and the method of organotypic cultivation was applied. Poisoning with convulsive poisons was modeled using 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride and the zinc complex of 1-butylvioluric acid was used as a drug for pharmacological correction of the effects of liver tissue damage. Results. The data obtained indicate that under the action of 2-(dimethylaminomethyl) phenyl ester of dimethylcarbamic acid hydrochloride, which simulates the effect of convulsive poisons on liver cells, their cell proliferation is inhibited. It was also found that the zinc complex of 1-butylvioluric acid eliminates the inhibitory effect of 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride on the proliferation of liver tissue culture. Research limitations. The study was performed on a culture of rat liver cells; to extrapolate data to the whole organism, it is necessary to take into account the data of toxicodynamics and toxicokinetics. Conclusion. Thus, the data obtained in the experiments prove the effectiveness of the use of the zinc complex of 1-butylvioluric acid as a drug for the pharmacological correction of the consequences of exposure to convulsive poisons, and also create a basis for its further study.