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Introduction: Convalescent COVID-19 patients have various signs of central nervous system damage, including those directly associated with SARS-CoV-2. Hence, studies of SARS-COV-2 related morphological changes in neocortex are particularly relevant for understanding the mechanisms of their formation and development of approaches to preclinical evaluation of the effectiveness of antiviral drugs. The purpose of the research is a longitudinal study of the ultrastructural alterations in Syrian hamsters neocortex after experimental SARS-CoV-2 infection., Materials and Methods: Male Syrian hamsters weighing 80100 g, aged 4 to 6 weeks, were infected with 26 l SARS-CoV-2 intranasally with 4104 TCD50/ml of viral particles. The animals were euthanized on days 3, 7 or 28 post-infection, the brain was extracted with the cortex excision. The material analysis was performed using transmission electron microscopy., Results and Discussion: On day 3 post-infection, the number of moderately hyperchromic neurons in neocortex increased, while by the day 7 the number of apoptotic cells significantly increased. Simultaneously, an increased signs of neuronophagy and representation of atypical glia were observed. Increased number of altered oligodendrocytes was observed on day 28 post-infection. Viral invasion was accompanied by changes in neocortical cells since day 3 post-infection, such as transformation of their nucleus, the rough endoplasmic reticulum and the Golgi vesicles as well as microvascular spasm with perivascular edema., Conclusion: As a result of electron microscopic study, the ultrastructural alterations in neocortex were described in an experimental model of SARS-CoV-2 infection. The findings can be used to identify the mechanisms of infection pathogenesis and to search for the new directions in development of medicines.

Introduction: Verification of histological changes in respiratory system using Syrian (golden) hamsters (Mesocricetus auratus) as experimental model is an important task for preclinical studies of drugs intended for prevention and treatment of the novel coronavirus infection COVID-19.The aim of this work was to study pathological changes of pulmonary tissue in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) experimental infection in Syrian hamsters., Material and Methods: Male Syrian hamsters weighting 80-100 g were infected by intranasal administration of culture SARS-CoV-2 at dose 4 × 104 TCID50/ml (TCID is tissue culture infectious dose). Animals were euthanatized on 3, 7 and 14 days after infection, with gravimetric registration. The viral load in lungs was measured using the polymerase chain reaction (PCR). Right lung and trachea tissues were stained with hematoxylin-eosin and according to Mallory., Results and Discussion: The highest viral replicative activity in lungs was determined 3 days after the infection. After 7 days, on a background of the decrease of the viral load in lungs, a pathologically significant increase of the organ's gravimetric parameters was observed. Within 3 to 14 days post-infection, the lung histologic pattern had been showing the development of inflammation with a succession of infiltrative-proliferative, edematousmacrophagal and fibroblastic changes. It was found that initial changes in respiratory epithelium can proceed without paranecrotic interstitial inflammation, while in the formation of multiple lung parenchyma lesions, damage to the epithelium of bronchioles and acinar ducts can be secondary. The appearance of epithelioid large-cell metaplastic epithelium, forming pseudoacinar structures, was noted as a pathomorphological feature specific to SARS-CoV-2 infection in Syrian hamsters., Conclusion: As a result of the study, the specific features of the pathology of the respiratory system in SARSCoV-2 infected Syrian hamsters were described. These findings are of practical importance as reference data that can be used for preclinical studies to assess the effectiveness of vaccines and potential drugs.

Properties of nanoscale carriers recommended by the European Pharmacopeia for use in the creation of drugs and their complexes with physiologically active substances are given. Ihe authors present general descriptions of the methods of creation and especially of carriers identified in the accumulation of experience in their use for creating drugs with desired properties of penetration of biological barriers and length of service of the therapeutic effect.

On selection of external bleeding models for preclinical evaluation of the effectiveness of local haemostatic agents (literature review). To temporarily stop of external bleeding traditionally use a pressure bandage or tourniquet, but not for all types of wounds it is possible and appropriate to apply these dressings. In recent times there has been significant progress in the development and improvement of local haemostatic agents used for the first aid. There are currently conflicting information about their effectiveness, presented by various authors, requires standardization of experimental modelsforpre-clinical testing of medical devices in this class. Following a review of domestic and foreign literature DroDosed to standardize external bleeding model for assessing the effectiveness of local haemostatic agents.

The state research and test institute of military medicine of the Ministry of Defence of the Russian Federation celebrates the 85th anniversary. The article is devoted to the anniversary of the newly reconstituted state research and test institute of Military Medicine of the Ministry of Defence of the Russian Federation. The institute was closed down in 2011 and worked exclusively as a structural subdivision of the Kirov Military Medical Academy for tests of ergonomic characteristics of a weapon and military equipment. Recreation of the institute allowed to engage highly qualified personnel and change the range of tasks, identified prospects of fundamental and applied researches in the field of development of hemostatic agents and anaesthetics, physiology of military work, medical robotics, development of technical means for medical services, and development of new medical technologies. The authors formulated prospects of development of the institution and its participation in the implementation of the primary tasks of the Medical Service to preserve and improve the health of military personnel.

The article describes the way medical service dealed with problems resulted from the use of chemical weapons during the First World War (1914-1918). It was revealed that many of the abovementioned problems remain unsolved up to the present moment. It is stated the existence of the threat of use of chemical weapons in modem military conflicts, which expands the area of responsibility for medical chemical protection. The authors proved necessity and algorithm of the training system, considered as a part of medical protection in case of adverse factors of chemical nature.

The paper presents an overview of cellular therapy products and medical tissue engineering of the leading countries of the world (including the US) and identifies lines of research in the field of cellular technology application in the interests of national military medicine. The authors gave information concerning practical implementation of the achievements of biomedical research in the field of regenerative cellular products and technologies in Russia as different products, which may be used at the stages of medical evacuation. The authors presented results of research, which was, performed on the model of mine blast injury in accordance with principle possibility of the usage of cellular technologies products (multipotent mesenchymal stromal cells) in medical practice.

Authors consider causes of low efficiency of antidote therapy and ways of pharmacological tolerance management during medical treatment of organophosphate poisoning. One of the promising ways is a preventive antidote on the base of enzyme agents and allosteric modulators of a cholinesterase activity. Authors showed a expediency of a study of new acetylcholinesterase reactivators, its compositions and ways of drug delivery. Authors specified ways of searching for anticonvulsants from classes of quick-closing benzodiatines and NMDA-antagonists. Authors defined ways of improvement of methods of special antidotes delivery with targeted transport system. Authors made an assumption about the necessity of symptomatic treatment.

Application of robotic technology to the needs in the medical service of the Armed Forces. Further development of the medical service is inseparably associated with the implementation of robot technology into the practice of medical support of the Armed Forces of the Russian federation. For this purpose it is necessary to create a clinical scientific research centre of robot technology and interdepartmental scientific research simulation training center on the basis of the Kirov Military Medical Academy. It is also necessary to provide development of medical robotic complexes of tactical level of the medical service.

Technological parameters for the effective encapsulation of n-(1-phenethyl-4-piperidyl)propionanilide in poly(lactid-co-glycolide) (PLG) nanoparticles have been determined. Depending on the ratio of drug fractions adsorbed on the particle surface and associated with the polymer matrix, n-(1-phenethyl-4-piperidyl)propionanilide (200 microg/kg, i/m) loaded PLG nanospheres accelerated time onset and increased duration of sleep in rats: by a factor of 1.6 - 2.0 for polymer associated drug fraction within 40 - 60% and by a factor of 2.2 - 2.6 for polymer associated drug fraction within 60 - 80%. A similar increase of sleep duration was observed when free n-(1-phenethyl-4-piperidyl)-propionanilide was administered at doses within 400 - 500 microg/kg.

The effect of memantine administration has been studied on the model of mice poisoning with an anticholinesterase compound. It is established that the memantine action is due to its influence on the cholinesterase activity in the brain, blood plasma, and erythrocytes in addition to its NMDA-blocking action. Memantine promotes oxime-induced erythrocyte enzyme reactivation on the model of mice poisoning with anticholinesterase compound (0.8 LD50).

Aim: Study the ability of Chlamydia trachomatis and Chlamydophila pneumoniae to damage structures of eye posterior segment, features of development of such infectious process, its morphological and clinical characteristics., Materials and Methods: 6 rabbits with confirmed absence of C. trachomatis, C. pneumoniae were used in the study. 3 animals were infected with C. trachomatis culture and 3 animals--with C. pneumoniae culture. Subconjunctival and intravitreal mode of infectious agent introduction were used, as well as instillation of its culture into conjunctival sac. Microbiological diagnostics included microscopy with direct immunofluorescence, culture method and determination of antibody titers. Infectious process was studied by using ophthalmologic methods and histological examination. Observation period was 4 months., Results: In all the animals a development of infectious process at early stages after the infection was confirmed. Conjunctivitis symptoms, inflammatory exudation into vitreous humor, chorioretinal inflammation loci, disorders in transparency of optical media and detachment of retina were clinical manifestations. In 2 animals infected with C. trachomatis severe panuveitis was noted. In 4 animals infectious process assumed subclinical characteristics (infection with both C. trachomatis or C. pneumoniae). In pathomorphologic studies data on the ability of C. trachomatis and C. pneumoniae to cause damage to cells of retina, pigment epithelium and choroid were obtained., Conclusion: C. trachomatis and C. pneumoniae may play a significant role in pathology of vitreous humor, retina, pigment epithelium and choroid.

Combined administration of caffeine and ketorolac (NSAID) is accompanied by all possible types of drug interaction. Side effects of the drug combination are mostly due to the action of ketorolac and manifested by decompensated renal failure and progressive endotoxemia within 3 - 7 days after single administration of drugs. Thus, the amplification of ketorolac effects by caffeine must be taken into consideration in prescribing NSAIDs.

The antioxidant properties of sulfur-containing substances have been experimentally studied in vitro. Unithiol exhibits a wide spectrum us radicals. For this reason, unithiol can be considered, along with ascorbic acid, as a universal drug for the reduction of free radical reactions.

The clinical and pathomorphological features of vitreous retinochorioidal complex lesion with the pathogen Chlamydia pneumoniae were studied. Three rabbits (6 eyes) were infected with Ch. pneumoniae strain TWAR by instillation, subconjunctivally and 2 eyes were infected by intravitreally. Contamination was controlled by direct immunofluorescence and cultivation (conjunctival scrapes, venous blood). A postmortem study was conducted 128 days later, by employing an immunohistochemical analysis. On days 7-14, all cases showed the signs of a uveal reaction; 4 cases developed chorioretinitis. In 2 cases, the process ran as endophthalmitis with minimal clinical manifestations. The rate of the process was decreased by days 40-50. On the postmortem study, all the cases displayed lymphocytic-macrophageal infiltration in the vitreous body and retina in the presence of retinal focal dystrophic changes. An immunohistochemical study revealed the pathogen in different retinal layers (both inside and outside the chorioretinal foci) in all 6 cases and in the preretinal layers of the vitreous body in 5 cases. The pathogen Ch. pneumoniae is rather highly tropic to the structures of the visual organ and it is able to induce chronic lesion of the structures of the posterior portion of the eye portion with varying clinical manifestations. Dystrophic changes in infected tissues, the vitreous body and chorioretinal complex in particular, are a result of a chronic inflammatory process.

The investigation was undertaken to study changes in the structure of the vitreoretinal complex in experimental chlamydial infection. Six rabbits were inoculated with Ch. pneumonia (6 eyes) and Ch. trachomatis (6 eyes) via instillations, subconjunctivally and intravitreally. Clinical and pathomorphological study was conducted during 128 days, by using immunohistochemical techniques. All modes of inoculation resulted in the development of an intraocular infectious process as uveitis, choriorenitis, and vitreitis (endophthalmitis) of varying degrees--from subclinical to severe. Immunohistochemical study revealed the pathogen in the structures of the ocular posterior segment and in venous blood in all cases. When locally inoculated, chlamydial infection becomes disseminated, by afflicting the ocular posterior segment, no matter what the mode of inoculation is applied. The clinical picture of the lesion widely varies from subclinical manifestations to a severe process.

Using histological and electron microscopical methods, the state of intramural nervous structures of jejunum and rectum was studied in 92 dogs with experimental portal hypertension. Three phases of changes of portal pressure were detected and its influence upon the intramural nervous apparatus was observed. In phase 1 (first 4-5 days after the surgery) the reactive changes of the nervous apparatus were shown that were more pronounced in jejunum. In phase 2 (day 5 to 2.5 months) the portal pressure was shown to drop; this was accompanied by some signs of regeneration in jejunum and by an aggravation of destructive processes in rectum. In phase 3 of the repeated rise of portal pressure (2.5 to 6.5 months after the surgery), destructive changes in the nervous apparatus were demonstrated that were similar to those found in phase 1. However, the differences in the reaction of nervous structures in different layers of intestinal tube and the heterogeneity of the changes of the nervous apparatus in jejunum and rectum were absent. The association of time of appearance and of severity of structural changes with the elevation of portal pressure suggests the significant role of vascular factor in the morphogenesis of alterations observed in phase 3 of hemodynamic changes.

The authors present results of studying the effectiveness of a new class of medicines--preparations of the group "Glutoxim" (Molixan, Redoxell, Bikvolit, Liglutin) obtained on the model of experimental cirrhosis of the liver in 76 white rats caused by dimethylnitrosamin, and describe their first experience with using thiopoietins in 24 patients with cirrhosis of the liver in a surgical clinic. It was found that three weeks of treatment with Molixan and Bikvolit gave a significant hepatoprotecting effect (less amount of the connective tissue, reduction of the dystrophic processes in hepatocytes). A positive effect of Redoxell was shown in longer time of treatment. When used in clinic therapy with thiopoietins was followed by correction of the T-cell link of immunity in most patients. One of the most important results of treatment with medicines of the group of thiopoietins was a substantial improvement of the quality of life of the patients.

Threat of accident development at the chemical industry objects, as well as tasks of medical support in chemical weapon destruction necessitate improvement of the toxicant biological indication methods, creation of protective-decontaminating prescriptions to protect open areas of skin, and also development of etiotropic and pathogenetic therapy agents for poisonings The Scientific-Research-Test Center (Medicobiologic Protection) studies of every of the above trends have allowed to create and introduce into table medical support of the RF Armed Forces some new indication-means samples, antichemical packets, antidotes and means of pathogenetic therapy for convulsive and bronchospastic syndromes, to motivate use of pharmacological agents to stop toxic pulmonary edema and cardio-vascular failure.

The results of studying the pharmacokinetics of aminostigmine, a new reversible cholinesterase inhibitor produced in Russia, are discussed. Tissue radioactivity after intragastric administration of a toxic dose of aminostigmine was quite quickly absorbed from the intestinal lumen. The half-life period of aminostigmine exceeded considerably that of earlier studied carbamates and correlated with the clinical manifestations of the drug effects. This confirms that the use of aminostigmine in the treatment of neurologic and somatic diseases is preferable.