Background. For preclinical studies of drugs a relevant task is the selection of specific biochemical markers reflecting damage to the central nervous system, both in toxicological and pharmacological experiments. One of such markers may be protein S100b, the level of which will make it possible to assess the damage of the central nervous system of various genesis. Objective. The aim of the study was to assess changes in the level of S100b protein in the blood and in brain homogenates in brain tissue injuries of various genesis. Design and methods. The study was conducted on males of outbred rats and mice. A total of 62 animals were used: 47 rats and 15 mice. To determine the concentration of S100b protein, ELISA kits Rat S100b/S100 beta Elisa kit (Sandwich Elisa) were used) for rats and Mouse S100b/S100 beta Elisa kit (Sandwich Elisa) for mice. Statistical analysis was performed using licensed GraphPad Prism 9 software. Results: Changes of protein S100B was explored on models of alcohol neuropathy, bilateral and focal cerebral ischemia, traumatic brain injury. Forming of all pa[1]thologies led to increasing of protein S100B both in blood plasma and in brain tissues in case of traumatic brain injury. For alcohol neuropathy, focal and cerebral ischemia and traumatic brain injury changings of this marker level reached statistic meaning. Conclusion. Increased concentration of S100b is a sign of neuronal damage as a result of ischemic, traumatic and toxic factors, as well as in hypoclycemic conditions. Thus, protein S100b can be used in preclinical studies as a marker of brain damage, responding to damage of various genesis in studies of pharmacodynamics and pharmacological safety of drugs.
The article describes the advantages and features of experimental models of thermal burns using in vitro, ex vivo and in vivo test systems. An objective assessment of the application of each approach depending on the type of study is given. For example, cell culture models are simple but do not fully reflect the structure of human skin, which limits their translational value. Ex vivo models, such as skin explants, provide the necessary architectonics to study intercellular interactions, but they also have drawbacks, primarily related to short viability. In general, in vitro and ex vivo models have limitations in reproducing all aspects of burn wound pathogenesis and healing. In this regard, laboratory animals, primarily mice, rats, and pigs, are widely used to study burn wound pathology, its effects on the body, and the efficacy of therapy. The decision to use experimental animal models is made taking into account their translational relevance to humans. In rodents, wound healing occurs mainly by contraction, in contrast to the re-epithelialisation and granulation seen in humans, which contributes to faster wound healing in rodents. The significant similarities between certain properties of pig and human skin make the latter a relevant test system in pharmacodynamic studies of thermal burn wounds.
Several treatment regimens with antituberculosis medicinal products are available for tuberculosis. Thiozonide is a newly developed original antimicrobial agent that exhibits bacteriostatic activity against Mycobacterium tuberculosis strains H37Rv, CN-37, CN-40, and MS-115.The aim of the study was to investigate the embryotoxic, foetotoxic, and teratogenic effects of thiozonide in pregnant rabbits.Materials and methods. The study involved 66 pregnant rabbits (4 groups of 16–17 animals each). The rabbits received oral thiozonide from day 6 to day 19 of gestation at doses of 20.6 mg/kg (1 TD (therapeutic dose)), 103 mg/kg (5 TDs), and 206 mg/kg (10 TDs). The control group received a 1% starch solution. The authors conducted a macroscopic examination of the reproductive organs and a histological evaluation of the placenta in eutha nised pregnant rabbits. Live foetuses underwent a check for developmental abnormalities, a skeletal development evaluation with a modified Dawson’s method, and a histologic examination of the internal organs.Results. The study showed no clinical signs of toxicity and no mortality associated with thiozonide in pregnant rabbits across all dose groups. Macroscopic and histological examinations revealed no pathological changes in the reproductive organs of pregnant rabbits. The evaluation of embryotoxic and foetotoxic effects did not identify any differences between the foetuses of the animals assigned to different doses of thiozonide and the control group. The authors found no developmental abnormalities in the foetuses. Examinations of foetal skeleton development and internal organ condition identified no differences between the groups and no abnormalities. The authors registered the death of all foetuses (late resorption) in one rabbit from the 206 mg/kg group. Therefore, the 103 mg/kg dose (5 TDs) was selected as a reasonable No Observed Adverse Effect Level (NOAEL).Conclusions. Thiozonide has no embryotoxic, foetotoxic, or teratogenic effects.
According to the latest data from the International Diabetes Federation (IDF), the number of patients with diabetes has outpaced previously predicted growth rates and is expected to increase by 51% by 2045. Thus, the development and evaluation of the effectiveness and safety of hypoglycemic agents is an urgent task due to the high social significance of the problem. In preclinical studies there are many models of experimental diabetes mellitus in animals, both with the use of chemical inducers that cause damage to the islet apparatus of the pancreas, and with the use of diets. According to the literature data, gerbils and degus are prone to hyperglycemia and insulin resistance when fed on standard laboratory diets, which are relatively high in calories compared to the food obtained by these animals in their natural habitat. Due to this feature the experimental induction of diabetes mellitus in these animal species can be modeled only through the use of a high-calorie diet. The purpose of this study was to test this hypothesis. Male and female gerbils of two age categories (14–20 and 40–41 weeks), as well as male and female degus, whose age was 65–70 weeks, were used as experimental animals. During the experiment the following indicators were evaluated: the concentration of glucose, cholesterol, triglycerides, creatinine, urea in blood plasma, the activity of dipeptidyl peptidase type 4 (DPP-4) and the parameters of the glucose tolerance test. Based on the totality of all experimental data a state close to pre-diabetic was established in male and female degus fed on a high-carbohydrate diet. This conclusion was made due to an increase in the activity of the DPP-4 enzyme and the presence of glucose tolerance by the 12th week of the experiment. The induction of experimental diabetes mellitus or latent diabetes mellitus using high-calorie diets failed in the majority of experimental animals (gerbils and degus) regardless of age. The obtained results are suggestive of the motivation for the use of these experimental models for the creation of experimental diabetes.
Burns are a severe and widespread type of injury and are accompanied by local and systemic complications, leading to disability and death. Infection is a major complication of burn injury because thermal burns can cause disturbances of humoral and cellular immunity, and necrotized tissue ceases to perform its normal barrier function, which leads to the development of infection caused by environmental opportunistic microorganisms and commensals, which limits the ability of the skin to heal. In addition, the scab of a burn wound is a nutrient-rich environment that is easily colonized by microorganisms. Gram-positive bacteria are the first colonizers of the wound bed because they make up the microflora of the skin microbiome. Burn wounds are most commonly associated with Staphylococcus aureus, which is capable of producing virulence factors that slow wound healing. The frequency of thermal injuries and their subsequent infection necessitates the creation of new therapeutic agents as well as the development and adaptation of relevant model systems for preclinical studies. A sufficient number of in vivo models have been developed to study the pathogenesis of burn injuries, as well as to conduct specific studies as part of preclinical studies of potential therapeutic agents. Rats are an adaptable model for reproducing infected burn wounds and evaluating their course. The aim of the study was to evaluate the pathogenesis of infected burns, allowing further use of this model pathology in the study of a wide range of potential antiseptic and anti-burn agents. The study successfully generated a model of infected skin burn in Wistar rats. Creation of burn wounds was carried out by contact method, the inducing damage temperature was 100 °C, Staphylococcus aureus ATCC 25923 was used as an infectious agent. Evaluation of the dynamics of the course of an infected burn wound was carried out according to the results of planimetric, microbiological, cytological and histological studies. The developed model of an infected skin burn in rats is relevant to study the pharmacological activity of antiseptic agents and local anti-burn agents with an antimicrobial component of the mechanism of action.
Relevance. Under the influence of endogenous and /or exogenous factors, the intestinal microflora inhabiting all parts of the gastrointestinal tract may change, which disrupts the normal course of physiological processes, and in some cases leads to severe pathological conditions. One of the reasons for the development of intestinal dysbiosis is the use of antibacterial drugs. Thus, the search and development of means for the prevention and treatment of dysbiosis is an urgent task. Goal. The aim of the study was to evaluate the effectiveness of a candidate for a calcium lactate-based drug with repeated intragastric administration on a model of antibiotic-induced dysbiosis in rats. Methods. The study used 40 male Wistar rats (four groups of 10 animals each). A model of antibiotic-induced intestinal dysbiosis was tested in rats by a course of intragastric administration of a combination of amoxicillin and clavulanic acid for 7 days at a dose of 75 mg/kg. The development of dysbiosis was confirmed by a change in the quantitative composition of representatives of the intestinal microbiota. Similarly, for 7 days, the test drug was administered in doses of 5 mg/kg, 25 mg/kg, 125 mg /kg daily 2 hours after the introduction of the pathology inducer. The control group received a 1 % starch solution. Results. The peak of dysbiosis development was recorded on the 4th day of pathology induction. The use of calcium lactate at a dose of 5 mg/kg did not have a significant effect, while in the groups receiving calcium lactate at doses of 25 mg/kg and 125 mg/kg, there was a statistically significant (Mann-Whitney criterion, p < 0.05) decrease in the severity of the pathological process compared with the negative control group. Conclusion. According to the results of this study, it was found that the use of calcium lactate in doses of 25 mg/kg and 125 mg/kg contributed to a faster disappearance of symptoms of dysbiosis and normalization of the intestinal microbiota in comparison with animals that did not receive treatment.
Bile acids are important signaling molecules involved in the regulation of lipid and glucose metabolism, maintenance of metabolic and energy homeostasis. Mice, rats, guinea pigs and rabbits are used as model organisms in pharmacodynamic studies. This is due to the availability of these animals, economic benefits and anatomical features of the hepatobiliary system. Notable differences in bile acid composition between laboratory animals and humans can play an important role and can reduce the translational value of data obtained using a particular test system. The choice of a particular animal species for pharmacodynamic studies of potential therapeutic agents should be based on several factors, which may include anatomo-physiological similarity of the hepatobiliary system and biochemical features of bile. It is these factors that are fundamental in the study of new pharmacologic agents and interpretation of the data obtained. The aim of the review is to compare some species-specific anatomo-physiological features of the hepatobiliary system, as well as to highlight the main aspects of bile production and bile acid metabolism in the most commonly used laboratory animals (mice, rats, guinea pigs and rabbits) both among themselves and with those in humans. Mice and rats are fairly common test systems, but the presence of muricholic acids limits their translatability. In addition, the small body size of mice can cause difficulties in the operative manipulations associated with the bile sampling procedure. The use of rats in contrast to mice does not cause such difficulties, but they lack a gallbladder, which accounts for the anatomical difference with the human hepatobiliary system. The rabbit has an optimal body size and anatomical similarity of the biliary system to that of humans, but the quantitative predominance of biliverdin and deoxycholic acid is a factor in the differences from humans. The guinea pig also has an optimal body size and anatomical similarity to the human hepatobiliary system, a high rate of choleresis and a generally similar bile acid composition, and a sufficient number of experimental model pathologies have been developed for it. The described qualities of laboratory animals, comparability or differences from those in humans indicate the need for a reasonable choice of a relevant test system taking into account the peculiarities of each of them.
Introduction. In Russia, almost half of the cases of acute intestinal infections of established etiology in 2022 are due to rotavirus infection (RVI). There is no specific treatment for rotavirus gastroenteritis. There is a need to develop modern, effective and safe vaccines to combat rotavirus infection that are not capable of multiplying (replicating) in the body of the vaccinated person. A promising approach is to create vaccines based on virus-like particles (VLPs). Objective. Study of the safety and immunogenicity of a vaccine against rotavirus infection based on virus-like particles of human rotavirus A in newborn minipigs with multiple intramuscular administration. Materials and methods. Newborn minipigs were used as an animal model in this study. The safety of the tested vaccine was assessed based on thermometry data, clinical examination, body weight gain, clinical and biochemical blood parameters, as well as necropsy and histological examination. When studying the immunogenic properties of the Gam-VLP-rota vaccine in doses of 30 and 120 µg, the cellular, humoral and secretory immune response was studied. Results. The results of assessing the general condition of animals during the immunization period, data from clinical, laboratory and pathomorphological studies indicate the safety of the vaccine against human rotavirus infection based on VLP (Gam-VLP-rota) when administered three times intramuscularly. Good local tolerance of the tested vaccine was demonstrated. The results of the assessment of humoral immunity indicate the formation of a stable immune response after three-time immunization with Gam-VLP-rota, stimulation of the production of antigen-specific IgG antibodies and their functional activity to neutralize human rotavirus A. It was shown that following the triple immunization with the minimum tested concentration of 30 µg/dose, animals developed a cell-mediated immune response. The results of the IgA titer in blood serum and intestinal lavages indicate the formation of both a systemic immunological response and the formation of specific secretory immunity to human rotavirus A. Conclusion. Thus, three-time intramuscular immunization of minipigs with the Gam-VLP-rota vaccine forms stable protective humoral and cellular immunity in experimental animals. Evaluated vaccine is safe and has good local tolerability.
The high prevalence of fungal skin infections motivates expanding the range of sertaconazole products for ex-ternal use. The aim of the study was a preclinical comparison of the safety, antifungal activity, and pharmacokinetics of Sertaverin® 2% medicated shampoo (VERTEX JSC, Russia) with those of Sertamicol® 2% solution for external use (Glenmark Pharmaceuticals Ltd, India) and Nizoral® 2% shampoo (Janssen Pharmaceuticals N.V., Belgium) approved in the Russian Federation. Materials and methods. In the toxicity study, the medicinal products were applied to the skin of male and female outbred rats at doses of 0.5 or 1.5 mL/animal for 28 days. The authors evaluated the pharmacokinetics of two sertaconazole formulations (shampoo and solution) following a single administration to adult male rats at the same dose. Nizoral® was not used in the pharmacokinetics study because it contains a different active substance, ketoconazole. The minimum inhibitory concentration (MIC) was determined using the serial microdilution method in a wide range of concentrations. Results. The medicinal products did not exhibit any significant toxic effects in laboratory animals after 28 days of repeated dermal application. Plasma sertaconazole concentrations were negligible. Sertaconazole was intensively distributed in the liver, which is a highly vascularised organ, and in the target organ (skin at the site of application). The relative bioavailability of sertaconazole from the shampoo relative to that from the solution for external use was approximately 30% in liver tissues and approximately 363% in skin tissues at the application site. Sertaverin® was comparable to sertaconazole in the active substance form in terms of inhibiting the growth of Malassezia furfur strains. The MICs calculated on the active substance basis were ≤16–64 μg/mL. Conclusions. With its synergistic dual mechanism of action, broad-spectrum antifungal activity, lipophilic properties, and low systemic absorption, Sertaverin® may provide a more effective and safe alternative to marketed medicinal products for scalp diseases.
Finding effective and safe medicines to fight SARS-CoV-2 infection is an urgent task. RPH-137 is an original trap fusion protein against SARS-CoV-2 virus. It comprises the angiotensin-converting enzyme type 2 extracellular domain and the human IgG1 Fc fragment.The aim of the study was to carry out a preclinical evaluation of the efficacy of RPH-137 and molnupiravir against SARS-CoV-2 infection.Materials and methods: the authors analysed RPH-137 expressed in a stable CHO cell line and molnupiravir used as an active pharmaceutical ingredient. Drug-mediated inhibition of virus-induced cytotoxicity was assessed in Vero cell culture. In vivo efficacy assessments were performed in Syrian hamsters. The animals were infected intranasally with SARS-CoV-2 (PIK35 clinical isolate) in the dose of 5 log TCID50. The authors evaluated body weight measurements, lung–body weight ratios, and lung histopathology findings and determined viral RNA levels in oropharyngeal swabs by RT-PCR using the amplification cycle threshold (Ct). The statistical analyses involved one- and two-way ANOVA, Student's t-test, and Mann–Whitney test.Results: RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells; the EC50 values of RPH-137 amounted to 4.69 μg/mL (21.3 nM) and 16.24 μg/mL (73.8 nM) for 50 TCID50 and 200 TCID50, respectively, whereas the EC50 values of molnupiravir were 0.63 μg/mL (1900 nM) for both doses. Intramuscular RPH-137 (30 and 80 mg/kg) had no effect on the infection process in Syrian hamsters. The comparison with the challenge control group showed that intraperitoneal RPH-137 (100 mg/kg) had statistically significant effects on a number of parameters, including a 27% reduction in inflammation and a 30% reduction in the total lesion area of the lungs by Day 7. Intragastric molnupiravir (300 mg/kg twice daily) significantly inhibited SARS-CoV-2 infection.Conclusions: both RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells. In Syrian hamsters, molnupiravir demonstrated a more pronounced inhibition of SARS-CoV-2 infection than RPH-137. However, RPH-137 had statistically significant effects on a range of parameters. This offers additional perspectives for further research.
Currently, there are no effective and safe medicinal products for idiopathic male infertility. Previous studies in two animal models of infertility (short-term cryptorchidism in rats and doxorubicin-induced testicular injury in mice) have shown the effectiveness of an originator medicinal product based on the mesenchymal stromal cell (MSC) secretome.The aim of the study was to evaluate the toxicity profile of the MSC secretome-based medicinal product in rats after local intratesticular or intramuscular administration.Materials and methods. The MSC secretome is a combination of factors secreted by MSCs in low-glucose Dulbecco’s modified Eagle’s medium (DMEM-LG) for MSC conditioning. In the single-dose toxicity study, the MSC secretome-based medicinal product was injected under the testicular tunica albuginea of male Wistar rats (15 per group) at doses of 15 and 25 relative units (RU) per animal, which are 1.5 and 2.5 times higher than the therapeutic dose (10 RU). In the repeat-dose toxicity study, male Wistar rats (10 per group) received intramuscular thigh injections of the medicinal product on days 1, 6, and 12 at doses of 15 and 25 RU per animal. The local tolerance study involved histopathological examination of the testes and thighs at the injection site. All studies included control groups of intact animals and animals similarly injected with blank DMEM-LG. The early follow-up period was 14 days, and the late follow-up period was 42 days.Results. The rats showed no changes in the general condition after single and repeated doses of the MSC secretome-based medicinal product. Single subtunical doses induced moderate irritation; its signs included pathological changes in individual seminiferous tubules: epithelial atrophy (70% of the animals on day 14; 55% at late follow-up) and sperm stasis (70% of the animals). Similar changes were observed in the blank DMEM-LG group (up to 80% of the animals). There were no pathological changes in the tissues after repeated injections. A transient increase in alkaline phosphatase activity was detected in animals after their third intramuscular injection at a dose of 25 RU; the other biochemical parameters were normal in all study groups.Conclusions. The MSC secretome-based medicinal product has a favourable safety profile following both intratesticular and intramuscular administration, as it does not cause any permanent changes in the studied organs and tissues.
Background. Sore throat of infectious and inflammatory origin is one of the most common reasons for the prescription of antimicrobial drugs. The use of antimicrobial peptides (AMPs) for topical therapy may be a promising solution, due to the peculiarities of AMPs’ mechanism of action, taking into account the high importance of microbial resistance spread problem in relation to systemic etiotropic drugs.The aim of the study was to assess the formation of resistance to AMP Gramicidin S (GS) of clinical isolates of Streptococcus pneumoniae and Staphylococcus aureus, including strains resistant to antimicrobial drugs during repeated exposure, in the setting close to their actual use in clinical practice.Materials and methods. The object under study is AMP GS. The test microorganisms are reference strains of S.pneumoniae (ATCC 6303), S.aureus (ATCC 6538–P), and 10 strains of clinical isolates of each type of microorganisms, types with antimicrobial resistance (including MRSA). At the first stage, the antimicrobial activity of GS was evaluated by the method of microdilutions in plates by estimating the value of the minimum inhibitory and the minimum bactericidal concentrations (MIC and MBC, respectively). At the second stage, using reference strains and 4 clinical isolates of each microorganism, including types with antimicrobial resistance, resistance was formed in two ways simultaneously (with liquid and solid media) for 7 consecutive passages over 7 days with GS at concentrations equal to 0.5 and 1.0 MIC. The number of surviving microorganisms was estimated and the MIC and MBC were determined at each passage.Results. At the first stage, the MIC of GS in relation to S.pneumoniae was 8 µg/ml for 5 strains, 16 µg/ml for 5 strains, and 4 µg/ml for one. For 10 out of 11 strains of S.aureus, including MRSA, the MIC of GS was 4 µg/ml (for 1 strain — 8 µg/ml). For 4 strains of S.pneumoniae, MBC of GS was equal to MIC (16 µg/ml), for 7 strains MBC was 4–8 times higher than MIC, and mostly amounted to 32 µg/ml (for 1 strain — 64 µg/ml). MBC for 6 strains of S.aureus was equal to MIC (4 µg/ml), for the 5 remaining strains MBC was 2–8 times higher than MIC, but did not exceed 64 µg/ml. At the second stage, it was found that the estimated values of GS MIC and MBC with repeated exposure to GS remained at the same level for 7 passages in all strains, including those resistant to antibiotics in liquid and solid media.Conclusions. Gramicidin S demonstrated high bactericidal activity against reference strains and clinical isolates of leading pathogenic microorganisms S.pneumoniae and S.aureus, including strains resistant to systemic antimicrobial drugs, while MIC and MBC did not exceed concentrations contained in single doses of drugs used in clinical practice. During repeated exposure (7 passages in 7 days), there were no signs of the formation of resistance of test strains of pathogens, including those resistant to systemic antimicrobial medicines from the groups of beta-lactams, macrolides, fluoroquinolones, tetracyclines, aminoglycosides, etc.
The effect of a bacterial lysate complex IRS 19 on local and systemic manifestations of inflammation was studied in a rat model of aseptic lymphadenitis. Injection of λ-carrageenan into the cervical lymph node via surgical approach caused an increase in the thickness of the capsule, disturbances in histoarchitecture, the appearance of necrosis foci, histiocytosis of subcapsular and cerebral sinuses in the lymph node, as well as an increase in the level of TNFα in the blood serum and the number of circulating leukocytes and neutrophils. Course intranasal administration of bacterial lysate complex in this model dose-dependently reduced the level of these markers of the systemic inflammatory response and the severity of microstructural disorders in the affected lymph nodes. Thus, bacterial lysate complex after intranasal administration produces a systemic anti-inflammatory effect that goes beyond the respiratory tract.
The high prevalence of fungal skin infections motivates expanding the range of sertaconazole products for external use.The aim of the study was a preclinical comparison of the safety, antifungal activity, and pharmacokinetics of Sertaverin® 2% medicated shampoo (VERTEX JSC, Russia) with those of Sertamicol® 2% solution for external use (Glenmark Pharmaceuticals Ltd, India) and Nizoral® 2% shampoo (Janssen Pharmaceuticals N.V., Belgium) approved in the Russian Federation.Materials and methods. In the toxicity study, the medicinal products were applied to the skin of male and female outbred rats at doses of 0.5 or 1.5 mL/animal for 28 days. The authors evaluated the pharmacokinetics of two sertaconazole formulations (shampoo and solution) following a single administration to adult male rats at the same dose. Nizoral® was not used in the pharmacokinetics study because it contains a different active substance, ketoconazole. The minimum inhibitory concentration (MIC) was determined using the serial microdilution method in a wide range of concentrations.Results. The medicinal products did not exhibit any significant toxic effects in laboratory animals after 28 days of repeated dermal application. Plasma sertaconazole concentrations were negligible. Sertaconazole was intensively distributed in the liver, which is a highly vascularised organ, and in the target organ (skin at the site of application). The relative bioavailability of sertaconazole from the shampoo relative to that from the solution for external use was approximately 30% in liver tissues and approximately 363% in skin tissues at the application site. Sertaverin® was comparable to sertaconazole in the active substance form in terms of inhibiting the growth of Malassezia furfur strains. The MICs calculated on the active substance basis were ≤16–64 μg/mL.Conclusions. With its synergistic dual mechanism of action, broad-spectrum antifungal activity, lipophilic properties, and low systemic absorption, Sertaverin® may provide a more effective and safe alternative to marketed medicinal products for scalp diseases.
The endocrine system coordinates almost all organs and other systems in vertebrates. In particular, it regulates such important biological functions as metabolism, development, reproduction, and behaviour. To date, a significant amount of information has accumulated on endocrine disorders associated with chemical compounds (endocrine disruptors) used in various fields of human activity. The aim of this work was to evaluate the possibility of preclinical risk assessment for the endocrine function disorders attributable to new medicinal products. Endocrine disruptors are associated with a wide range of adverse events, including developmental problems arising from functional abnormalities of the endocrine system. Endocrine disorders caused by endocrine-disrupting chemicals are characterised by a long latency period between exposure and manifestation of a dysfunction; a nonlinear dose–response relationship; and a linear correlation of damage severity to exposure timing and duration. The chemicals influence the endocrine system through multiple mechanisms, the main of which being the interaction with cellular receptors sensitive to certain hormones and the influence on gene expression, intracellular signalling, and hormone transport, etc. This paper discusses the possibility of using hormone levels as indicators of endocrine disruption and presents the literature and authors’ own data on normal levels of relevant hormones in the blood of animals. An analysis of animal blood hormone levels in preclinical programmes will provide an opportunity to evaluate potential iatrogenic risks.
Routinely the influenza virus significantly contributes to the formation of the annual incidence of acute respiratory infections, with a peak in winter season. The high level of mutagenic potential of influenza viruses is a standard factor determining the complexity of the rational choice of pharmacotherapy. The upcoming epidemiological season 20202021 brings additional challenges for health care practitioners mediated by the widespread prevalence in the human population of a new infection caused by the SARS-CoV-2 virus affecting the respiratory system among many organs and systems. An adequate choice of pharmacotherapy tools should be based on high efficiency and safety of drugs, with a possible reduction in such negative factors as polypharmacy. This review includes comparative pharmacological characteristics of drugs with activity against RNA viruses, along with parameters of their clinical efficacy.
Routinely the influenza virus significantly contributes to the formation of the annual incidence of acute respiratory infections, with a peak in winter season. the high level of mutagenic potential of influenza viruses is a standard factor determining the complexity of the rational choice of pharmacotherapy. The upcoming epidemiological season 2020 2021 brings additional challenges for health care practitioners mediated by the widespread prevalence in the human population of a new infection caused by the SARS-CoV-2 virus affecting the respiratory system among many organs and systems. An adequate choice of pharmacotherapy tools should be based on high efficiency and safety of drugs, with a possible reduction in such negative factors as polypharmacy. This review includes comparative phamiacological characteristics of drugs with activity against RNA viruses, along with parameters of their clinical efficacy.