Accelerated Method for Determining Ischemic Brain Damage in Rats and Assessment the Neuroprotective Effect of a Complex Herbal Remedy.

The severity of ischemic injury was evaluated by densitometry of brain samples stained with 2,3,5-triphenyltetrazolium chloride (TTC) on a rat model of cerebral ischemia/reperfusion (common carotid artery occlusion) and the neuroprotective activity of an extract of Astragalus membranaceus, Scutellaria baicalensis, and Phlojodicarpus sibiricus was assessed. Occlusion of the common carotid arteries led to a weakening of TTC staining of the brain tissue: densitometric indicators of the staining intensity for the cortex and striatum were lower than the corresponding indicators of sham-operated rats by 18.3 and 10.4%. The mean intensity of staining of brain samples did not differ in rats treated with the extract and sham-operated animals, which attested to its neuroprotective effect. The applied method is convenient for evaluation of the severity of ischemic brain damage at the early stages and screening potential neuroprotective agents.

EEG Microstate Analysis and the EEG Inverse Problem Solution as a Tool for Diagnosing Cognitive Dysfunctions in Individuals Who Have Had a Mild Form of COVID-19.

The term "postcovid syndrome" is firmly entrenched in medical terminology, however, many aspects of its clinical manifestations are not well understood. The aim of this work was to find the causes of the development of cognitive dysfunctions in individuals who had a mild form of SARS-CoV-2 using high-density EEG technology and solving an inverse neurophysiological problem. A dynamic study was conducted of 38 people who had COVID-19 and returned to work. Neurophysiological studies were carried out using the EGI-GES-300 system (128 channels). The descriptive characteristics of electroencephalograms were built on the method of studying the spectral density of the EEG signal on the surface of the scalp, and the dynamic characteristics of the signal were studied by fixing EEG microstates, using the method of D. Lehmann and T. Koenig (2018). In the study, a relatively new diagnostic technique for studying cognitive impairments based on the analysis of EEG microstates was implemented, which made it possible to identify signs of functional restructuring of the neuronal macronetworks of the brain and trace the characteristic adaptation of a person during the period of convalescence. The results obtained made it possible to detect a violation of the implementation of the speech function, as a violation of the perception system (ventral information flow system), as well as the connection between the fields of Wernicke's center and Broca's center (dorsal information flow system), leading to the development of communicative dysfunctions that cause characteristic clinical symptoms due to impaired perception of new information and difficulties in implementing the solution. Thus, the survey showed that SARS-Co-V2 causes objective changes in the functional activity of the brain, which are manifested by the syndrome of cognitive dysfunction and require the development of more sensitive clinical tests than currently used.

Preclinical Studies of Immunogenity, Protectivity, and Safety of the Combined Vector Vaccine for Prevention of the Middle East Respiratory Syndrome.

The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.

[Clinicopatological variants and risk factors for chronic kidney disease in rheumatoid arthritis].

Recent studies have shown a high risk of chronic kidney disease and associated cardiovascular complications in patients with rheumatoid arthritis (RA), which determines the prognosis. However, the prevalence of chronic kidney disease (CKD) in RA has not been established in the Russians. AIM: Study was to examine the prevalence, risk factors and histological variants of CKD in RA. MATERIALS AND METHODS: 180 patients with rheumatoid arthritis were observed in the Tareev clinic of nephrology, for the period from 2014 to 2019 years. Age, gender, duration of RA, drug therapy, ESR, CRP, DAS28, renal function, proteinuria, histological variants were analyzed. Of the common population risk factors for CKD arterial hypertension, weight index, serum lipids and glucose levels were also assessed. RESULTS: The prevalence of CKD in RA was 19.7%. Age, presence and stage of arterial hypertension, an increase in body mass index, as well as high rates of disease activity ESR, CRP, DAS28 score and duration of RA were risk factors of CKD in RA. Age, duration of the disease, stage of AH and hypercholesterolemia were risk factors in multifactorial regression analysis. Amyloidosis was the most common histologic pattern (50.0%), followed by chronic glomerulonephritis (30.4%) and tubulo-interstitial nephritis (19.6%). Among chronic glomerulonephritis mesangial glomerulonephritis was the most frequent. Renal amyloidosis was associated with a duration of RA, presence of systemic symptoms and CRP level. An isolated decrease in GFR of less than 60 ml/min was detected in 31 (36.0%) out of 86 patients. Сonclusion. The risk factors for CKD in patients with RA are activity and duration of the disease In addition to common population factors. Amyloidosis was the most common histologic pattern associated with duration of RA and inflammatory proteins levels.

Assessment of the Parameters of Adaptive Cell-Mediated Immunity in Naïve Common Marmosets (Callithrix jacchus).

Common marmosets are small New World primates that have been increasingly used in biomedical research. This report presents efficient protocols for assessment of the parameters of adaptive cell-mediated immunity in common marmosets, including the major subpopulations of lymphocytes and main markers of T- and B-cell maturation and activation using flow cytometry with a multicolor panel of fluorescently labelled antibodies. Blood samples from eight common marmosets were stained with fluorescently labeled monoclonal antibodies against their population markers (CD45, CD3, CD20, CD4, CD8) and lymphocyte maturation and activation markers (CD69, CD62L, CD45RO, CD107a and CD27) and analyzed by flow cytometry. Within the CD45+ population, 22.7±5.5% cells were CD3- CD20+ and 67.6±6.3% were CD3+CD20-. The CD3+ subpopulation included 55.7±5.5% CD3+CD4+CD8- and 34.3±3.7% CD3+CD4-CD8+ cells. Activation and maturation markers were expressed in the following lymphocyte proportions: CD62L on 54.0±10.7% of CD3+CD4+ cells and 74.4±12.1% of CD3+CD8+ cells; CD69 on 2.7±1.2% of CD3+CD4+ cells and 1.2±0.5% of CD3+CD8+ cells; CD45RO on 1.6±0.6% of CD3+CD4+ cells and 1.8±0.7% of CD3+CD8+ cells; CD107a on 0.7±0.5% of CD3+CD4+ cells and 0.5±0.3% of CD3+CD8+ cells; CD27 on 94.6±2.1% of CD3+ cells and 8.9±3.9% CD20+ cells. Female and male subjects differed in the percentage of CD3+CD4+CD45RO+ cells (1.9±0.5 in females vs 1.1±0.2 in males; p < 0.05). The percentage of CD20+CD27+ cells was found to highly correlate with animals' age (r = 0.923, p < 0.005). The basal parameters of adaptive cell-mediated immunity in naïve healthy marmosets without markers of systemic immune activation were obtained. These parameters and the described procedures are crucial in documenting the changes induced in common marmosets by prophylactic and therapeutic immune interventions.

[Late-onset rheumatoid arthritis in a patient with successfully treated IgA nephropathy]. / Pozdnii debiut revmatoidnogo artrita u patsienta s uspeshno lechennoi IgA-nefropatiei.

The paper describes a rare clinical case of rheumatoid arthritis (RA) that developed in a patient 9 years after diagnosing IgA nephropathy. Kidney disease was characterized by a stable course with moderate urinary syndrome, hypertension, and reduced renal function. Immunosuppressive therapy using glucocorticosteroids and then mycophenolic acid led to remission of nephritis and recovery of renal function. However, the absence of nephritis activity and discontinuation of immunosuppressants was responsible for articular syndrome. The diagnosis of RA is based on its characteristic radiological patterns and immunological characteristics after ruling out a number of systemic diseases and infections. The common pathogenetic components of IgA nephropathy and RA, including the role of rheumatoid factor IgA, are discussed.

[Difficulties in the differential diagnosis of kidney injury in a patient with infective endocarditis associated with antineutrophil cytoplasmic antibodies]. / Trudnosti differentsial'noi diagnostiki porazheniia pochek u bol'nogo infektsionnym éndokarditom, assotsiirovannym s antineitrofil'nymi tsitoplazmaticheskimi antitelami.

Infective endocarditis (IE) may be accompanied by the production of a broad spectrum of autoantibodies, including antineutrophil cytoplasmic antibodies (ANCA). ANCA detection creates difficulties in the differential diagnosis of IE, especially in relation to kidney injury, the determination of the mechanism of which is important for choosing a treatment policy and estimating a prognosis. The paper describes a clinical case of a 57-year-old man who was found to have higher proteinase-3 (PR-3) ANCA titers along with the symptoms of anemia, purpura, and kidney injury during his hospitalization; echocardiography revealed vegetation on the aortic valve. IE was diagnosed; 2-week antibiotic therapy was ineffective; there was progressive aortic insufficiency necessitating aortic valve replacement. In the postoperative period, there was progression of renal failure and higher PR-3 ANCA titers, which made it possible to regard kidney injury as a manifestation of ANCA-associated glomerulonephritis. Intensive immunosuppressive therapy with intravenous and oral prednisolone was initiated, which showed positive effects in reducing proteinuria, erythrocyturia, serum creatinine levels, and simultaneously PR-3 ANCA titers. The paper gives the data available in the literature on the frequency of an association of IE with ANCA, the clinical features, diagnostic criteria, and treatment approaches. It discusses the mechanisms of ANCA formation in patients with IE.

[Takayasu's disease in an IgG4-positive patient with tuberculosis, pulmonary hemorrhage, recurrent myocarditis, and transient bilateral visual impairments]. / Bolezn' Takayasu u IgG4-pozitivnogo patsienta s tuberkulezom, legochnym krovotecheniem, retsidiviruyushchim miokarditom i prekhodyashchimi dvustoronnimi zritel'nymi narusheniyami.

Takayasu's disease (nonspecific aortoarteritis) affects the absolute majority of 20-40-year-old women; its most common manifestations include aortic arch branch lesions. The specific features of the described case is the male gender of the patient, signs of mesenchymal dysplasia, a concurrence of tuberculosis, pulmonary hemorrhage, and myocarditis at onset, the presence of IgG4, peculiar ocular symptomatology, and its rapid regression after initiation of therapy.

The AUSTRAL VLBI observing program.

The AUSTRAL observing program was started in 2011, performing geodetic and astrometric very long baseline interferometry (VLBI) sessions using the new Australian AuScope VLBI antennas at Hobart, Katherine, and Yarragadee, with contribution from the Warkworth (New Zealand) 12 m and Hartebeesthoek (South Africa) 15 m antennas to make a southern hemisphere array of telescopes with similar design and capability. Designed in the style of the next-generation VLBI system, these small and fast antennas allow for a new way of observing, comprising higher data rates and more observations than the standard observing sessions coordinated by the International VLBI Service for Geodesy and Astrometry (IVS). In this contribution, the continuous development of the AUSTRAL sessions is described, leading to an improvement of the results in terms of baseline length repeatabilities by a factor of two since the start of this program. The focus is on the scheduling strategy and increased number of observations, aspects of automated operation, and data logistics, as well as results of the 151 AUSTRAL sessions performed so far. The high number of the AUSTRAL sessions makes them an important contributor to VLBI end-products, such as the terrestrial and celestial reference frames and Earth orientation parameters. We compare AUSTRAL results with other IVS sessions and discuss their suitability for the determination of baselines, station coordinates, source coordinates, and Earth orientation parameters.

[MORPHOMETRIC EVALUATION OF THE NEUROPROTECTIVE EFFECT OF THE EXTRACT OF ASTRAGALUS MEMBRANACEUS ON THE BRAIN OF RATS SUBJECTED TO IMMOBILIZATION STRESS].

The aim of the study was to analyze histological and morphometric changes in the brain of rats subjected to immobilization stress and to assess the neuroprotective effect of the extract of Astragalus membranaceus (AE). The work was carried out on Wistar rats that were divided into 3 groups (6 animals in each): group 1 ­ intact rats; group 2 ­ control animals subjected to immobilization stress for 18 h; group 3 ­ rats treated orally with AE (50 mg/kg) for 7 days and then subjected to immobilization stress. The level of stress-induced brain damage was assessed by a morphometric method, by measuring the proportions of morphologically intact neurons, hyperchromatic shrunken neurons and neurons with the signs of degeneration in layers III­V of the cerebral cortex and CA1 region of the hippocampus in the standard area of the section. Immobilization stress in rats led to a clearly pronounced neuronal damage in the cerebral cortex and hippocampus. AE was found to limit the stress-induced neuronal damage in the cerebral cortex and the hippocampus: the proportion of hyperchromatic shrunken neurons was reduced 3 and 4.6 times, respectively, compared to control.

Morphological Analysis of Neurovascular Changes in the Brain in Unilateral Occlusion of the Common Carotid Artery.

Morphological analysis of changes in the brain structures of rats with unilateral occlusion of the common carotid artery showed vascular disorders and neuronal involvement in the anteroparietal cortex and hippocampal CA1 filed on the ipsilateral side.

CHRONIC TOXICITY ASSESSMENT OF HIPOLIPIDAEMIC HERBAL EXTRACT / Монголын эм зүй, эм судлал

Aim of the study: The present study was car- ried out to evaluate the safety of a hipolipidaemic herbal extract by determining its potential toxicity after chronic administration in rats.Materials and Methods: The hipolipidaemic herbal extract was administered orally at doses of 50, 150 mg/kg daily for 90 days to rats. Bio- chemical and morphological parameters were determined after 90 days of daily administration. Results: In the chronic study in rats, daily oral administration of the extract for up to 90 days did not result in death or significant changes in the biological, biochemical and morphological parameters. Conclusions: The results showed that the hypolipidaemic herbal extract had no toxicity in oral chronic administration and indicate that the herbal formula could be considered safe for oral medication. Key words: Herbal hypolipidaemic extract, chronic toxicity. Introduction In the present time, there has been a great in- crease in the use of herbal remedies in the treat- ment of diseases [1, 2]. Many traditional plants with therapeutic lipid-lowering properties are claimed to be useful in the treatment of hyperlipi- demia and associated pathologies [3, 4, 5]. The hipolipidaemic herbal composition (extract) con- sists of ten herbs: fruits of Rosa canina L., Cra- taegus sanguinea Pall., Elettaria cardamonum L.and Malus baccata L., roots and rhizomae of Glycyrrhiza glabra L., Zingiber officnale, såminà Lini usitatissimi L., folia Îrthosiphoni staminei Benth. and other. Chronic toxicity study of this hipolipidaemic herbal extract was performed in rats in order to evaluate the safety. Material and methods Wistar rats of both sexes aged 1-1.5 months toxicity assessment. Animals were divided into 3 groups (I–III) of 10 each (5 females and 5 males). The extract, dissolved in distilled water, was ad- ministered by daily oral for 90 days, to rats of groups II-III (doses of 50, 150 mg/kg, respec- tively). I group was control (distillate water). The animals were observed for signs of toxicity and mortality throughout the experimental period. The body weigh were recorded weekly. At the end of the 90-day experiment, rats of each group were sacrificed by decapitation under anaesthe- sia (sodium thiopental 50 mg/kg). Blood was col- lected for biochemical studies respectively. The organs (brain, heart, lung, liver, spleen, kidneys) were weighted and compared with the value of control. Organ samples (kidney, pancreas, lung and liver) were fixed in 10% formalin for histo- pathological examination.

[Severe adverse events from treatment with genetically engineered biological agents in patients with rheumatic diseases].

AIM: To assess the risk of severe adverse events (AEs) within 6 months after treatment with biological agents in patients with rheumatic diseases (RD). SUBJECTS AND METHODS: The 6-month open-label trial included 107 patients with rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, and other RDs who received genetically engineered biological agents (GEBAs), primarily rituximab (n = 66) and infliximab (n = 31). RESULTS: The majority of patients were noted to have improvements, including complete and partial remission in 62 (57.9%) and 42 (39.3%), respectively. There were mild or moderate AEs in 22 (20.6%) of the 107 patients, severe AEs in 6 (5.6%): grade IV neutropenia in 2 patients (after the use of rituximab), severe infusion reactions in 2 (after the administration of infliximab and rituximab), and systemic infections in 2 (fatal nocardial sepsis after rituximab treatment and unspecified sepsis after infliximab treatment). CONCLUSION: The rate of serious AEs, mainly infusion AEs and infections during treatment with infliximab, rituximab, and other GEBAs proved to be relatively low in patients with different RDs. At the same time, the use of biological agents could lower RD activity in the presence of severe visceral injuries refractory to conventional immunosuppressive therapy.

Morphological assessment of the cerebroprotective action of lanthanum acetate in chronic cerebral ischemia in rats.

The aim of the present work was to perform a morphological assessment of the cerebroprotective action of lanthanum acetate in chronic cerebral ischemia in rats. Chronic ischemia was produced in Wistar rats (weighing 160-180 g) by ligation of both common carotid arteries. Ischemic lesions were corrected by intragastric lanthanum acetate (3 mg/kg per day) throughout the experimental period. Ischemic damage to the cortex was assessed morphometrically on histological sections stained by the Nissl method. Lanthanum acetate was found to suppress the development of ischemic neuron damage in the cerebral cortex, with reductions in the numbers of hyperchromic neurons, cells with focal chromatolysis, and ghost cells, as well as an increase in the number of normochromic cells as compared with controls.