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Vol 19, No 3 (2021)

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Silver nanoparticles: safety and efficiency for human health

Morozova Y.A., Dergachev D.S., Subotyalov M.A.


Over the past few decades, nanoparticles of metals, and in particular silver, with a diameter of less than 100 nm have significantly expanded their field of application for various biomedical purposes. So, silver nanoparticles have great potential in a wide range of applications as antimicrobial agents, coatings for biomedical products, carriers for drug delivery, bioengineering, since they have discrete physical properties and wide biochemical functionality. Studies have shown that the size, morphology, stability and properties (chemical and physical) of metal nanoparticles are strongly influenced by the conditions of the experiment, the kinetics of the interaction of metal ions with reducing agents and the adsorption processes of the stabilizer with metal nanoparticles. This review aims to analyze the use of silver nanoparticles in modern medicine based on data from domestic and foreign literature over the past five years. The study confirmed the high biological activity of drugs with nanoserebrum as anti-inflammatory, antimicrobial agents, antifungals, the presence of an inhibitory effect on protozoa, antioxidant and anticancer effects, and substantiated the relevance of use in bioengineering and dentistry. However, rapid advances and advances in technology have led to concerns about the potential risk associated with the use and application of silver nanoparticles to human health and the environment. Therefore, this review attempts to characterize and quantify the potential harmful effects of silver nanoparticles on the health of laboratory animals and humans, and focuses on ways to neutralize or reduce the toxic effects of silver nanoparticles on the human body.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):247-257
pages 247-257 views

Possibilities of pharmacological correction of reperfusion injury of ischemic myocardium (review)

Gurevich K.G., Urakov A.L., Fisher E.L., Abzalilov T.A., Khairzamanova K.A., Yagudin T.A., Samorodov A.V.


Timely and effective reperfusion in ischemia and reoxygenation in hypoxia of the heart muscle prevent myocardial infarction. Delayed reperfusion and reoxygenation in myocardial ischemia and hypoxia can cause reversible damage in it, which, with a favorable outcome, disappear without a trace. Excessively late reperfusion and reoxygenation inevitably ends with irreversible damage to the myocardium, which is widely known as a myocardial infarction, and which, together with other complications of cardiac ischemia, can cause disability and death of the patient. In recent years, reperfusion injury of the ischemic heart muscle has been recognized as an independent link in the pathogenesis of myocardial infarction. The mechanisms of this link of pathogenesis have been partially studied in experimental conditions. The phenomena of preconditioning and post-conditioning have been discovered, the effects of which are currently determined fairly reliably. After determining the mechanisms of reperfusion injury of the ischemic myocardium, the search and development of pharmacological agents capable of inducing such a phenomenon as cardioprotection began. In parallel, studies of specific microRNAs that claim to be diagnostic markers are being conducted, as well as the search for drugs that affect the level of their expression is being conducted. The information about the achieved successes in this direction is given.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):259-267
pages 259-267 views

Mechanisms and triggers of adaptation to hypoxia

Lyubimov A.V., Cherkashin D.V., Efimov S.V., Alanichev A.E., Ivanov V.S., Kutelev G.G.


It is believed that hypoxia-induced factor (HIF1) is the key mediator of oxygen metabolism. It was first identified as a transcription factor activated in cells and tissues by lowering the partial pressure of oxygen (O2). The HIF1 activator spectrum includes both external factors – hypoxia, psycho-emotional stress and in ternal factors and varies from hormones to iron chelators. This review is dedicated to the molecular mechanisms of HIF1 activation, some of its natural activators HIF1, the potential for which is due to the low level of toxicity and the reduced likelihood of undesirable side effects. In turn, this opens up new options to treat diseases associated with local and general ischemia and hypoxia, the possibilities of their prophylactic use for researchers and clinicians in order to reduce the degree of damage in the event of an unforeseen condition of acute injurious to organs and tissues by hypoxia and reperfusion after it.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):269-280
pages 269-280 views

Antioxidant and prooxidant systems in patients with ischemic insult

Belokoskova S.G., Tsikunov S.G.


The literature review presents current information on the role of oxidative stress in the pathogenesis of cerebral ischemia / reperfusion. In patients with ischemic stroke, activation of enzymatic and non-enzymatic links of antioxidant defense in the form of an increase in the blood and cerebrospinal fluid of the activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, the content of glutathione reflects the presence of compensatory reserves, is a favorable factor for the restoration of brain functions. An increase in the content of markers of lipid peroxidation in various biological environments in patients with strokes, mainly malondialdehyde, even in combination with an increase in the content of markers of antioxidant protection, indicates its insufficiency and an unfavorable prognosis of the disease. An increase in the content of markers of lipid peroxidation, mainly malondialdehyde, in patients with strokes in various biological environments, even in combination with an increase content in markers of antioxidant protection, indicates its insufficiency, an unfavorable prognosis of the disease. The presence of affective disorders and the persistence of residual manifestations of ischemic stroke may be due to permanent oxidative stress. When choosing a therapy aimed at increasing the activity of antioxidant protection and reducing the toxic effect of prooxidants, one should take into account the severity and dynamics of metabolic disorders. In the presence of data reflecting insufficient activity of antioxidant systems in combination with increased activity of prooxidant systems, the appointment of drugs that reduce the severity of oxidative stress in the early stages of stroke is indicated. Therapy including antioxidant drugs is also indicated in patients with post-stroke affective disorders and with residual symptoms of stroke.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):281-290
pages 281-290 views

Molecular mechanisms of antiatherogenic drugs action

Lizunov A.V., Bychkov E.R.


The purpose of this review is the analysis of the molecular mechanisms of lipid metabolism, their disorders leading to atherosclerosis, and the influence of modern antiatherogenic and antihyperlipidemic agents on atherogenic mechanisms. At the beginning of the review, a general description of atherosclerosis as pathology, its main characteristics and factors is given. The question of the complexity of the treatment of atherosclerosis and the problems arising in connection with the complexity is considered. Current models of the nature of atherosclerotic lesions are described. Next, we consider modern anti-atherosclerotic drugs used in clinical practice. Their nomenclature is given. Their basic biochemical mechanisms and the nature of their action are analyzed. Their negative effects and side effects are also considered. Then, the molecular and genetic mechanisms associated with atherosclerosis are analyzed in detail. The genes associated with lipid metabolism and the formation of atherosclerotic plaques, their expression and regulation are considered. The question of the influence of known anti-atherosclerotic agents on their expression is also covered. A group of azole drugs and their effect on lipid metabolism are considered in the context of the search for new anti-atherogenic drugs. The final part of the review examines the relevance of the search for new anti-atherosclerotic agents and methods for modeling dyslipidemia as a model of conditions that correlate with anti-atherosclerotic vascular lesions. It was concluded that the search for antiatherogenic drugs among imidazole derivatives is promising.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):291-301
pages 291-301 views

Original articles

The role of N-cholinoreceptors in somatovisceral intersystemic interactions in early rat ontogenesis

Sizonov V.A., Dmitrieva L.E., Kuznetsov S.V.


Interaction of slow-wave rhythmic components of cardiac, respiratory and motor activities was analyzed in non-narcotized of newborn 1-day-old (P1) and 16-day-old (P16) Wistar rat pups under normal and impaired cholinergic regulation. Functional activity of these three systems is rhythmic, and coordination of their functioning is an important element of the mechanism of adaptive rearrangements under changing factors of the external and internal environment. The acetylcholinesterase inhibitor physostigmine (eserine) was used to increase the level of endogenous acetylcholine and enhance cholinergic effects. To reveal the role of N-cholinoreceptors in intersystemic somatovisceral interactions (ISI), we performed blockade of this receptor type with benzohexonium. Administration of physostigmine leads to the development of a number of pathological reactions and a decrease in the level of ISI in all ranges of modulating rhythms in rats of both ages. ISI in younger rats appear to be more resistant to changes in the level of cholinergic activation. Blockade of N-cholinoreceptors causes inhibition of ISI at P1 and partially to their potentialization at P16. The activation of cholinoreactive structures, which occurred against the background of cholinoreceptors blockade, reduces the pathological effects of physostigmine in animals of both ages, but at the same time leads to an attenuation of ISI. This weakening is more pronounced in 16-day old rats, which may indicate the formation of the definitive level of cholinergic regulation in the first weeks of postnatal ontogenesis.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):303-312
pages 303-312 views

Retina photosensitivity indexes as an objective indicator of expression of psychostimulating effect

Ovanesov K.B., Shabanov P.D.


BACKGROUND: The variety of neurotransmitter systems providing photoreceptor capabilities of the retina is a prerequisite for studying the retinotropic properties of some psychotropic drugs, taking into account their ability to interfere with the work of synapses.

MATERIALS AND METHODS: Given this circumstance, a set of studies was carried out with the participation of volunteers to assess the effect of psychotropic substances with a stimulating (caffeine, piracetam, Bilobil®) type of action on the functional state of the retina, recorded by the campimetric method. In the course of the research, the photosensitivity of the retina, its ability to distinguish colors and the speed of the visual-motor reaction were assessed. Such an approach can not only demonstrate the interest of retinal cellular elements in the action of substances, but also broaden the question of the participation of the visual system in the psychopharmacological effect.

RESULTS: The function of the retina was studied both in healthy volunteers and in individuals with organic lesions of the central nervous system, which were often accompanied by emotional disorders, which were identified using special questionnaire tests. It was found that these pathological conditions are accompanied by a limitation of the photosensitivity of the retina of varying severity. These facts can be interpreted in different ways. On the one hand, violations of visual functions can lead to psychoemotional disorders and be a pathogenetic link in their development, and on the other hand, primary disorders of retinal light and color sensitivity can provoke the development of psychopathology. However, regardless of the pharmacological characteristics of the studied drugs that stimulate mental activity, the relationship of their effect with changes in visual function seems obvious, which makes it possible to raise the question of the advisability of taking into account the light and color sensitivity of the retina for a comprehensive assessment of both the mental state and the pharmacodynamics of the drugs, stimulating mental activity.

CONCLUSION: Thus, it is legitimate to conclude that taking into account the light and color sensitivity of the retina can be one of the quantitative criteria for the severity and effectiveness of psychopharmacotherapy.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):313-326
pages 313-326 views

Effect of the ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium on wound healing in thermal skin damage in rats

Khnychenko L.K., Piotrovskiy L.B., Shabanov P.D.


AIM: Of the investigation was to assess the therapeutic efficacy of ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium, an imidazol derivative, on healing of a thermal skin damage (burn wound) in rats.

MATERIALS AND METHODS: In experiments on 150 male rats weighing 180–200 g, the wound-healing effect of an ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium (IEM-1181) after experimental thermal skin damage was studied. The ointment containing 10% of the compound IEM-1181 was prepared by the pharmacopoeial method based on lanolin. The control was the placebo effect (the basis of the ointment). For comparison, we used Solcoseril© (ointment, Solco, Switzerland). Thermal damage to the skin of rats under ether anesthesia was carried out with a special device consisting of a metal plate and a temperature controller. The surface of the plate with a diameter of 1,5 cm was heated for 15 minutes to a temperature of 80°С, and then applied to the pre-cut skin of the rat’s back (from the scapula caudally) for 15 seconds. After 24 hours, the skin of the animals developed damage to the epidermis and partially underlying dermis, corresponding to a grade II burn. The dynamics of changes in the burn wound was evaluated by 5, 10, 15, 20, 30, 40, 45, 50, 60, 70 days along the length of the contour bounding the affected area, using a curvimeter.

RESULTS: It was found that 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium benzosulfonate has a wound-healing effect in thermal skin damage in rats. With topical application of the ointment containing the test compound, the time of complete healing of the wound formed at the site of the burn defect was reduced by 30%, healing took place without signs of inflammation, with the formation of an elastic scar.

CONCLUSIONS: Based on the conducted studies, it can be concluded that the ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) it has a wound-healing effect in thermal damage to the skin comparable in terms of the duration and degree of healing of burn defects with Solcoseril and can be the drug of choice for the treatment of grade II burns.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):327-332
pages 327-332 views

Dark cytotoxicity of submicrometer vaterite particles loaded with photosensitizer Fotoditazin and the vaterite-based core – shells structures

Verkhovskii R.A., Nechaeva O.V., Guslyakova O.I., Svenskaya Y.I.


Photodynamic therapy (PDT) is based on the use of photosensitizers together with a light at the wavelength corresponding to its absorption maximum. Photosensitizers are able to generate reactive oxygen species under the visible or infrared light irradiation. They are broadly used for the treatment of cancer and infections due to their physical and chemical properties. Dose-dependent light induced cytotoxicity of photosensitizers shows the strong relation between its concentration in the treatment area and PDT efficiency. With this regard, the development of novel carriers for targeted delivery of photosensitizers is a very prospective research direction, as allows for the enhancement of the local drug concentration in the treatment area and the reduction of the incidental dark toxicity in healthy tissue associated with a classic PDT. Mesoporous vaterite particles are considered as a promising tool for biomedical application due to their biodegradability, high payload ability, as well as to the simplicity and cheapness of their fabrication. The efficiency of vaterite carrier application for a PDT delivery system design has been previously demonstrated. With this regard, the current study was aimed at the evaluation of dark cytotoxicity of the submicron vaterite particles and the vaterite-based core-shells, both loaded with Fotoditazin® photosensitizer.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):333-338
pages 333-338 views

Anticompulsive effects of novel derivatives of coumarin in rats

Daliev B.B., Bychkov E.R., Myznikov L.V., Lebedev A.A., Shabanov P.D.


BACKGROUND: Until now, the neurotropic effect, in particular the effect on the emotional behavior of oxy-coumarins, has not been adequately studied. There are only few data on their central action. Currently, research is underway on the synthesis of new compounds based on natural oxy-coumarins, which will potentially have a higher biological activity.

AIM: Was to study the central action of new oxycoumarin-based compounds – IEM-2886, LVM-99, LVM-S144, in particular, on compulsive behavior in rats.

MATERIALS AND METHODS: To assess the behavior of Wistar rats, the “Marble-test” and “Elevated plus maze” methods were used. Oxycoumarin derivatives (IEM-2886, LVM-99, LVM-S144) were injected intraperitoneally at doses of 1, 10 and 25 mg/kg. The effectiveness of the drugs was judged by the number of balls buried in the “Marble test” and by the duration of staying in the open and closed sleeves of the “Elevated plus maze”. Results. It was shown that in the Marble test, oxycoumarin-based compounds (IEM-2886, LVM-99, LVM-S144) caused a decrease in the number of buried balls, which shows their anti-compulsive effect. After administration of IEM-2886, LVM-99, LVM-S144 (1–25 mg / kg) compounds, dose-dependent effects were observed (p < 0.05). The “elevated plus maze” test did not show the anxiolytic effect typical for tranquilizers. Moreover, after the administration of IEM-2886 and LVM-S144 at a dose of 25 mg / kg, an increase in the time spent in the closed sleeve of the maze (p < 0.05) was observed, i.e. an anxiogenic effect.

CONCLUSION: Thus, oxy-coumarin-based compounds are selective for the assessment of anticompulsive effects.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):339-344
pages 339-344 views

Clinical pharmacology

Mechanisms of prevention postoperative immunosuppression by regional anesthesia

Zabrodin O.N., Strashnov V.I.


The data on the factors of development of postoperative immunosuppression (PI) are presented. Among them, an important role in the development of PI belongs to hyperactivity during operations of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal system. It has been shown that PI is prevented by regional anesthesia, primarily epidural anesthesia and postoperative epidural analgesia, as well as prolonged ganglioplegia. It is concluded that the preventive action of regional anesthesia in relation to the development of PI is largely associated with the sympatholytic component of action.

Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):345-353
pages 345-353 views

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