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The article provides a collection of archaeological sites of the Bronze Age and the end of the Early Iron Age of the Volga-Ural region, in which artificially deformed skulls were found. At present, 33 such archaeological sites have been counted, of which 5 belong to the 25th – 22th centuries BC, and 28 – to the first half of the 1st millennium AD. Сertain similarity was noted in the methods of artificially deformation reproduction among the tribes of the Bronze Age and the Early Iron Age. The fixation of sites with manifestations of this rite far to the north of the main area of nomadic cultures of the Early Iron Age (burial grounds Ro- zhdestveno V, Narmonka, Burkovo I, etc.), the presence in some of them of heterogeneous anthropological complexes (Sidelkino), cases of artificial deformations of the head among the aboriginal population of forest-steppe and even forest cultures (the Azelino culture of the Kama region, the Kharino culture of the Perm territory) – all this is an important argument in favor of contacts between the nomadic and sedentary population on the eve and during the era of the Great Migration of Peoples. Form and nature of the contacts were different.

This article deals with events that took place in Kazan diocese in April — July, 1908. Their central figure is head of Kazanskaya Bogoroditskaya Sedmiozerskaya Pustyn’, archimandrite Gavriil (Zyrianov). The accusation of Revd. Gavriil, by that time widely known for his asceticism far beyond the borders of Kazan diocese, as well as of his spiritual child, hieromonk Tikhon (Buzov), the treasurer of the monastery, of negligent management of the household of the monastery and of accumulating considerable debts in the monastery that they were in charge of, resulted in the resignation of the head and his subsequent persecution by the ruling archpriest, archbishop of Kazan and Sviyazhsk Nikanor (Kamenskiy). The case received considerable attention in church circles of the diocese of that time. However, it was not studied properly, and materials kept in the archive of Kazan Spiritual Consistory were not scrutinised in terms of reconstructing the true circumstances of the events. Lack of a careful analysis of certain episodes led to a partial mythologisation of the history, confusion in facts, and, most importantly, made it impossible to identify all the participants of the confl ict, determine the line and specificity of their conduct, aims and motives. The future canonisation of archimandrite Gavriil (Zyrianov) in the rank of all-Russian saints requires to eliminate the historical lacunae, including in the ethical and anthropological perspective. This article attempts to deal with this task. It makes public a large number of previously unpublished sources. Their base if made up of documents kept at the State Archive of Republic of Tatarstan and in the library of Kazan (Volga Region) Federal University.

The authors examine the anthropological materials of the Sintashta and related cultures of the finale of the middle – the beginning of the late Bronze Age. Theoretical aspects of the problem of morphogenesis in these populations are presented in connection with archeological and genetic studies. The practical part is devoted to the analysis of new craniological sources from the burials of the Sintashta-Abashevo chronological horizon of the forest-steppe Urals. The materials of the collective burial near the village of Malojuldashevo and the burial ground Krasikovo I of the Orenburg region have being published for the first time. The authors determine the place of these populations among the synchronous forms of the Urals and the Volga region. Anthropological heterogeneity of the population has been shown and the prospect of joint archeological-anthropological and genetic studies for the reconstruction of processes of culturogenesis and morphogenesis is considered.

In 2017, excavation of burial ground Ekaterinovsky cape were continued, located in the area of the confluence of the Bezenchuk River in the Volga River. During the new excavations, 14 burials were studied. The skeleton of the buried were in a position elongated on the back, less often – crooked on the back with knees bent at the knees. In one burial (No. 90), a special position of the skeleton was recorded. In the burial number 90 in the anatomical order, parts of the male skeleton. This gave grounds for the reconstruction of his original position in a semi-sitting position with the support of elbows on the bottom of the pit. Noteworthy inventory: on the pelvic bones on the left lay a bone spoon, near the right humerus, the pommel of a cruciform club was found.The conclusion is made about the high social status of the buried. The results of the analysis of burial allow us to outline the closest circle of analogies in the materials of Khvalynsky I and Murzikhinsky burial grounds.

The paper presents the results of laboratory studies of a number of additives introduced during operation to motor oil of internal combustion engines. It also evaluates their impact on tribological characteristics of friction pairs. It was found that all studied additives have a positive effect on the running-in quality. Reduced wear of friction pairs, reduced surface roughness compared to base motor oil is determined. The best indicators were recorded with the FENOM additive. The decrease in wear was 46% and roughness – 23.5% compared to the base oil.

The urgency of the issue is reasoned by the necessity to develop environmentally friendly technologies and engineering tools for cleaning emerged mineral oil from insoluble impurities in order to reuse them in the nodes and auto-tractor equipment systems. Hydrocyclone is one of the simplest and most effective means of cleaning waste oil. In order to determine the possibility of hydrocyclone usage in technological lines for purifying oils, it is necessary to establish the influence of its geometrical parameters on the purification quality of such high-viscosity liquid as emerged mineral oils. The purpose of the article is to study theoretically the cylindro-conical hydrocyclone geometrical parameters influence on the purification degree of emerged high-viscosity mineral oils from insoluble and wear debris. The leading approach to the study of this problem is the consideration of the behavior of a non-soluble particle in an oil stream under the influence of forces acting on it, which allows identifying the geometric and regime parameters of a cylindro-conical hydrocyclon. These parameters have the greatest influence on the oil purification degree. The article presents a theoretical justification for the geometrical parameters influence of a cylindrical-conical hydrocyclone on the emerged oil purification degree, a separation criterion, which allows not only determining the optimal size of a hydrocyclone, but also conducting a comparative assessment of hydrocyclones with different geometric parameters by oil purification efficiency from insolubles. Theoretical researches are aimed at determining the cylindro-conical hydrocyclone geometric parameters, depending on the pollution intensity of the emerged mineral oil and the desired degree of its purification from insolubles.

The article is devoted to the solution of the problem associated with the partial substitution of marketable mineral diesel fuel (DF) with mixed vegetable-mineral (MDF) engine fuel. The bio-component of MDF is vegetable oil, for example, Camelina seed oil. A design option of a dual-fuel feeding system has been proposed, the main component of which is a mixing and metering unit for vegetable oil and mineral diesel fuel which allows electric metering units controlled by an electronic control unit (ECU) to respond to signals from diesel load-speed sensors (crankshaft speed, injector rack position (fuel injection pump)) and temperature gauge of camelina oil, to ensure the feed of mixed diesel fuel with components of different content. The use of mixed diesel fuel based on vegetable oil, containing for example 50 % of mineral commercial fuel and 50 % of camelina oil, makes it possible with a slight decrease in the effective power (not more than 6 %) and some increase in the specific effective consumption of mixed fuel (up to 14 %) to save 50 % of fuel of petroleum origin, as well as to reduce the smoke opacity of exhaust gases by 17–20 % and reduce the content of carbon oxide by 35–40 % compared with the work of a diesel engine on commercial mineral diesel fuel.

The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid molecules containing several pharmacophore fragments of different structures. This strategy is successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce side effects. In this work, we synthesized 10 1-aryl derivatives of benzimidazole and benzotriazole and 11 hybrids based on them. Among the compounds obtained, the most promising hybrid molecules were diphenylamines, containing an amino group and a benzotriazole cycle in the ortho position to the bridging NH group, which showed significant cytotoxic activity, excellent antioxidant properties and the ability to suppress the migration activity of tumor cells. Taken together, our results demonstrate that substituted diphenylamine-based bipharmacophoric compounds may serve as a promising platform for further optimization to obtain effective antitumor compounds.

Selective blocking of individual isoforms of carbonic anhydrase (CA) is now one of the main directions in the development of its inhibitors. The new 1,2,4-oxadiazole-containing sulfonamides B12 and B13 predominantly block CA II and CA IX. The study of acute toxicity of B12 and B13 showed their safety. Substance B13 caused a relatively short-term, but rapid (within 30 min) decrease in the intraocular pressure in rabbits, which indicates the promise of its use for the emergency decrease in the intraocular pressure in medical practice. Analysis of the effects of sulfonamides on the functions of CNS showed that compound B12 probably exhibit tranquilizing activity; B13 is promising for the creation of drugs that have an antidepressant effect and at the same time increase the mental and physical performance., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The results of preclinical studies of romiplostim analogue GP40141 are presented. The effect of a cell proliferation, phosphorylation of the TPO receptor and JAK2 phosphorylation were studied in the presence of romiplostim and in the presence of GP40141 in a cell line of mice (Mus musculus) lymphoblasts with stable expression of human TPO receptor 32D-hTPOR clone 63. Binding to the TPO receptor and to the neonatal Fc receptor (FcRn) was examined for both romiplostim and the developed analogue. In Sprague-Dawley rats, the dynamics of platelet count after the administration of romiplostim or GP40141 were determined. The pharmacokinetics of romiplostim and GP40141, as well as the dynamics of platelet count, were studied in cynomolgus monkeys. The serum concentrations of romiplostim were determined using a modified colorimetric enzyme-linked immunosorbent assay (ELISA). The data obtained allow us to assert the similarity of the biological action of Nplate® and GP40141., Competing Interests: Declaration competing of interest This study was funded by Geropharm, Russian Federation. The authors' team includes employees of Pharm-Holding (a scientific and practical subunit of Geropharm)., (Copyright © 2023 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Objective: Evaluation of the bioequivalence of the tested Relonova, tablets, 10 mg and Maxalt, tablets, 10 mg drugs on an empty stomach in healthy volunteers., Material and Methods: The pharmacokinetic analysis population included 40 volunteers, the safety analysis population included 40 volunteers. The average age of randomized volunteers (men - 20, women - 20) was 29.3±8.9 years, height 1.71±0.09 m, body weight 70.86±11.66 kg, mean BMI 24.18±2.81 kg/m 2 . The method used high performance liquid chromatography with tandem mass spectrometric detection. Statistical analysis of the obtained data was performed based on the assumption of a log-normal distribution of the parameters AUC0-72 and Cmax., Results: The ratio of geometric means for the key pharmacokinetic parameters (AUC0-t, AUC0-inf and Cmax) of rizatriptan is close to 90%, CI is within the acceptable range for bioequivalent drugs (80-125%). The intrasubject variability (CVintra) for rizatriptan was 23.74% (Cmax), 10.94% (AUC0-t). The average profiles of the pharmacokinetic curves of rizatriptan when taking the test and reference drugs have similar shapes. Relonova and reference Maxalt are bioequivalent., Conclusion: The results of the study make it possible to recommend Relonova for further clinical study and wide practical application.

This study includes modeling and simulation of insulin aspart pharmacokinetics (PK). The authors used PK data of biosimilar insulins-insulin aspart and biphasic insulin aspart 30/70-to develop a predictive population PK model for the insulins. The model was built via Monolix software, taking into account the weight-based dosing and the dose and body-weight effects on the parameters. The model-based simulations were performed using the R package mlxR for various administered doses and various ratios of insulin aspart forms for a better understanding of the insulin behavior. The optimal model was a 1-compartment model with a combination of zero- and first-order absorptions, with absorption lag for the soluble form of insulin aspart and first-order absorption for the insulin aspart protamine suspension. The assumption of identical behavior of 2 insulins at the distribution and elimination phases was made. The developed PK model was fitted successfully to the experimental data, and all fitted parameters displayed a moderate coefficient of variation. The PK model allows us to predict PK profiles for various doses and formulations of insulin aspart and can be used to improve the accuracy, safety, and ethics of novel clinical trials of insulin., (© 2022, The American College of Clinical Pharmacology.)

The study was carried out to assess the state of cardiologic care and to determine current vectors of its development in the region with low population density. The health care system of the Kostroma Oblast was determined as research base. The information and methodological foundation of the study was compiled according results of special studies of patients aged from 8 to 80 years (n=1,400). The combination of research methods was implemented. The main vectors of the modern development of the cardiology service are identified: regional automated monitoring of quality of cardiologic care with operational analysis of its potential by 25 conjugated factors; implementation of continuous quality management technology according proposed algorithm; implementation of the decision-making scheme with allocation of 10 alternatives of achieving effectiveness of medical care according 4 criteria (standard performance, clinical result achievement, patient satisfaction, resources saving);, implementation of personalized approach to patient management.

Purpose: To investigate the possibilities of pharmacoeconomic and pharmacogenetic factors monitoring to assess the effectiveness of treatment of a cardiological profile patients as a part of the implementation of a personalized approach., Material and Methods: 200 patients with arterial hypertension and CHD were examined. Pharmacotherapy was analyzed. ABC/VEN and DDD analysis, pharmacoeconomic analysis were applied. Genetic analysis of the polymorphism of the genes CYP2D6*4 and CYP2D6*10 encoding the subfamily of the cytochrome isoenzyme Р-450 was carried out. An original monitoring method was used to assess the effect of pharmacoeconomic and pharmacogenetic factors on the performance of cardiac care., Results: When conducting a pharmacoeconomic analysis of cases of cardiac care, it was found that the costs of drug therapy are significant and take over 10% of the total costs. However, its effectiveness is insufficient in 58% of cases in inpatient and 37% in outpatient care. The analysis showed that there is an inverse mean correlation between gene polymorphism and clinical performance of cardiac care (r = -0.62) and a direct strong correlation between polypharmacy in pharmacotherapy, not accounting for interdrug interaction and clinical performance (r = 0.89).

Aim: To compare safety (immunogenicity) and efficacy of a biosimilar insulin GP-Lis25 and a reference insulin Ly-Lis25 (Humalog Mix 25) in Type 2 diabetes mellitus (T2D) patients. Materials & methods: This randomized open-label, 26-week clinical trial enrolled 210 T2D patients, randomized 1:1 to twice-daily GP-Lis25 or Ly-Lis25. The primary end point was immune response at 26th week. Noninferiority margin for HbA1c was 0.4%. Results: Immune response frequency was similar in GP-Lis25 and Ly-Lis25 groups both at week 12 (p = 0.651) and 26 (p = 0.164). The difference of HbA1c change at week 26 was (95% CI) 0.01 (-0.27-0.28)%. Fasting plasma glucose, seven-point glucose profile and insulin dose were similar between groups. Safety did not differ between groups. Conclusion: GP-Lis25 and Ly-Lis25 demonstrated similar safety and efficacy. ClincalTrials.gov identifier: NCT04023344.

Introduction: Tuberculosis (TB) is one of the top ten causes of death worldwide. Improvement of the treatment options via development of new drugs and treatment regimens that would be more convenient for patients is one of key options of improving the effecacy of the TB prevention and careis. Since the creation of new treatment regimens by minimizing the number of the drugs used and reducing the duration of treatment is the most promising and correct direction, macozinone, a new candidate of the benzothiazinone series, can become the basis for development of new chemotherapy regimens for drug-resistant forms of TB including the combination of macozinone with the most effective modern anti-TB drugs., Aim: Comparative evaluation of the pharmacokinetic properties of macozinone capsules 80 mg and the new dosage form a dispersible tablet for preparation of oral solution., Materials and Methods: Solubility of the substance macozinone in biorelevant media in vitro, permeability of macozinone in the test Caco-2 in vitro, as well as pharmacokinetics of macozinone in dogs in vivo were evaluated., Results: The solubility assessment in biorelevant media showed that the average limit of macozinone substance dissolution in the pH 5.0 acetate buffer solution was from 6 to 9 mg/l, in FaSSIF medium (fasted) from 2.5 to 4 mg/l, and in FeSSIF medium (after meals) from 16.8 to 29 mg/l. It is established that the cell permeability of the pharmaceutical substance macozinone in the CACO-2 test system is on average 2.510-6cm/s in the forward direction from the apical to basolateral cell membrane, and 1.510-6cm/s in the reverse direction, which corresponds to low permeability. The main pharmacokinetic parameters of macozinone dispersable tablets 160 mg, after dosing with food and on an empty stomach, as well as capsules 80 mg, when administered on an empty stomach in vivo studies in dogs are presented., Discussion: The specific physicochemical properties of macozinone, the problems of developing the new dosage form, as well as ways of solving some of them are presented., Conclusion: In the process of new dosage forms development, the existing chemical properties of the macozinone substance should be considered. One of the promising ways of increasing bioavailability and, consiquently, efficacy is development a fundamentally new drug form with modified release within the absorption window.

Tuberculosis is a chronic infectious disease, usually localized in the respiratory system and representing one of the most important global social and biomedical health problems associated with the spread of therapy-resistant forms (multidrug-resistant and extensively drug-resistant tuberculosis). One of the most promising targets for the development of antimycobacterial drugs is the enzyme DprE1, which is involved in the synthesis of the cell wall of mycobacteria. In the series of DprE1 inhibitor drugs, the most advanced drug is PBTZ169 (INN maсozinone). Clinical trials (CT) of the efficacy and safety of macozinone are conducted by the pharmaceutical company LLC NEARMEDIC PLUS in the Russian Federation, and in other countries (Sponsors: Innovative Medicines for Tuberculosis Foundation, cole polytechnique fdrale de Lausanne and Bill and Melinda Gates Foundation). The publication describes results of completed I, IIa and Ib phases CT, conducted in the Russian Federation., Aim: The goal of phase I CT was to assess the safety, tolerability and pharmacokinetics (PK) of PBTZ169, 40 mg capsule, after single and multiple administration under fasting conditions in increasing doses in healthy volunteers. The goal of phase IIa CT was to study the efficacy (in terms of early bactericidal activity EBA), safety and PK of the drug PBTZ169, 80 mg capsules, in various doses, when used as monotherapy in patients with newly diagnosed respiratory tuberculosis with bacterial excretion and retained sensitivity to isoniazid and rifampicin. The purpose of phase Ib CT was to evaluate the safety, tolerability, PK of PBTZ169, 80 mg capsule, after single, double and multiple administration under fasting conditions in increasing doses, as well as the effect of food on its bioavailability in healthy volunteers., Materials and Methods: The data of 100 healthy volunteers and 15 patients with newly diagnosed pulmonary tuberculosis, who received the study medication PBTZ169, capsules 40 mg and 80 mg, in the dose range 40 mg 1280 mg of PBTZ169, obtained during phase I, IIa and Ib CTs were analyzed. During I phases CTs, safety, tolerability, and PK of the drug after a single and multiple administration under fasting condition and after meals at rising doses were evaluated. The safety assessment included evaluation of AE/SAE, vital signs, ECG results, and laboratory tests results in the safety population. In the course of phase IIa CT, in addition to safety, tolerance, and PK evaluation, the efficacy of the drug (in terms of EBA) using sputum culture on agar with CFU/ml counting (main method) and quantitative PCR method (auxiliary method) was evaluated., Results: During all CTs, a high safety and tolerability profile was shown, the main PK parameters of the drug and the efficacy were described. PBTZ169 demonstrated linear PK in the dosage range up to 640 mg after single and multiple administration, a statistically significant of EBA of the drug after monotherapy at the dose of 640 mg/day was demonstrate, and it was concluded that the preferred regimen of the drug PBTZ169 intake is administration after meals. Good tolerability and a favorable safety profile of the drug in the studied doses range were demonstrate during all the CTs., Conclusion: One of the most promising and currently studied drugs-inhibitors of DprE1, a new target for the cell wall of mycobacteria, is PBTZ169 or macozinone, which is being develop by the Russian pharmaceutical company NEARMEDIC PLUS ltd.

Aim: To compare safety (immunogenicity) and efficacy of GP40061 insulin glargine (GP-Gla) and Lantus ® (Sanofi glargine, Sa-Gla) in people with diabetes mellitus. Materials & methods: This randomized open-label, 26-week clinical trial enrolled 180 Type 1 diabetes mellitus patients (HbA1c 6.5-12.0%), randomized 1:1 to once daily GP-Gla (n = 90) or Sa-Gla (n = 90). The primary end point was immune response at 26th week. Results: The frequency of immune response was similar in GP-Gla and Sa-Gla (p = 1.000). Groups were similar in terms of other safety end points. Mean HbA1c change from baseline was -0.66% for GP-Gla and -0.77% for Sa-Gla, and did not differ between groups (p = 0.326). Insulin doses, fasting plasma glucose and seven-point glucose profiles were similar between groups. Conclusion: GP-Gla and Sa-Gla demonstrated similar safety and efficacy. ClinicalTrials.gov Identifier: NCT04022993.

We selected all case histories of patients living in the area served by the Syktyvkar policlinic #3 and treated in Republican Cardiological Dispensary in 2003-2009 with diagnosis of myocardial infarction (MI). Data on survival of patients after MI (mean duration of follow-up 4.6 years) was derived from information on date and cause of death of patients obtained from statistical office of the policlinic. Overall we analyzed data on 778 patients (46.3% women, mean age 63.7 years). For detection of independent factors related to lethal outcome we used binary logistic regression, for assessment of survival we used Kaplan-Meier method and Cox regression model of proportional hazards. From positions of gender differences we assessed pharmacoepidemiology of MI, efficacy of thrombolytic therapy, determined factors of hospital and long term mortality. No increase of risk of hospital or long term mortality associated with female sex was revealed by multifactorial analysis. Greatest prognostic significance in relation to unfavorable outcome irrespective of patients sex was established for the following factors: age, severity of MI course, severity of renal dysfunction. In acute period of MI in addition to these factors we revealed unfavorable influence of hyperglycemia and protective role of preceding hypertensive disease.

Aim: To study renal dysfunction in patients with myocardial infarction (MI)., Subjects and Methods: 670 case histories of patients diagnosed with acute coronary syndrome, including 369 (55.8%) men and 292 (44.2%) women at the age of 33 to 85 years (mean age 64.8 +/- 11.7 years), were retrospectively studied. The authors considered comorbidities and analyzed complaints, history data, and the results of physical examinations, biochemical blood tests for plasma glucose, troponin, MB fractions of creatine phosphokinase and creatinine, and cholesterol in all the patients. Instrumental studies involved electro- and echocardiography. Glomerular filtration rate (GFR) was estimated using the MDRD formula. The patients were divided into groups according to GFR values: 1) > 90 ml/min/1.73 m2; 2) 60 to 89 ml/min/1.73 m2; 3) 30 to 59 ml/min/1.73 m2; 4) less than 30 ml/min/1.73 m2., Results: Most patients were found to have a moderate or significant reduction in kidney function. Worsening renal function in patients with MI was associated with advanced patient age, the lower proportion of men in the patient structure, the higher prevalence of concomitant cardiovascular diseases, such as arterial hypertension, chronic heart failure, and prior MI, and diabetes mellitus., Conclusion: The findings suggest that kidney dysfunction is of essential value in developing the multiplicity of comorbidities in patients with MI. The wide introduction of a GFR calculating method in daily medical practice will be able to adequately and timely identify renal filtration function and to make a correction into a treatment regimen, thus decreasing the number of poor outcomes.

Aim: To characterize pulmonary lesion in systemic lupus erythematosus (SLE) on the basis of clinical device and biochemical examination regarding features of the disease onset and development., Material and Methods: The study included 60 SLE patients. Mean age 41.1 +/- 1.32 years. Mean SLE duration 12.42 +/- 1.06 years. Activity according to the SLEDAI and ECLAM indices--16.23 +/- 0.93 and 3.09 +/- 0.18 scores, respectively. The comparison groups: 30 patients with bronchial asthma (BA), 15--with chronic bronchitis (CB), 15--with chronic obstructive bronchitis (COB), 30 healthy donors. The following parameters were studied: spirometric, bodyplethismographic evidence, diffuse ability of the lungs (DAL), plasm concentrations of adrenaline, noradrenaline, dopamine, serotonine, histamine, hemodynamics, anxiety, depression, social adaptation (quality of life) and vegetative dysfunctions. Statistics were obtained with BIOSTATISTIKA program., Results: DAL depends on duration of SLE, severity of lung hypertension (LH), severity of anemia. LH in SLE deteriorated vegetative disorders and social adaptation. Lowering of plasm dopamine concentration was accompanied with LH, formation of vegetative dysfunction and worse social adaptation., Conclusion: Affection of the lungs in SLE patients runs without evident clinical symptoms. Initial signs of lung affection manifest with low DAL, LH, moderate restrictive, obstructive and mixed disorders of external respiration function.

Aim: Characterization of cerebral pathology in inactive phase of rheumatism., Materials and Methods: Clinical, experimental psychological examinations were performed in 110 rheumatic patients with inactive disease. Computer tomography of the head was carried out in 45 patients., Results: Psychic defects were absent only in 2.73% of the examinees. The rest had different neurotic symptoms manifest as panic attacks (> 50% of cases) or mildpsychoorganic shifts (60.91% of cases). Computer tomography of the brain has revealed hypodensive foci, deformed subarachnoid spaces and cerebral ventricles, hydrocephalia in 66.67% of the patients. These occurred more frequently in patients with psychoorganic syndrome or valvular heart diseases., Conclusion: Treatment and rehabilitation of rheumatic patients should also include measures to correct psychic and cerebral abnormalities frequently present in such patients.

A prospective study was made of environmental factors effects on unfavorable cardial and cerebral outcomes of rheumatic fever (RF) assessed functionally, biochemically and psychologically. Some of RF predisposing factors (female sex, frequent nasopharyngeal infections, poor housing and occupational conditions) negatively affect outcomes of primary RF and contribute to emergence of valvular disease. The initial attack of activity I or III degree, pronounced carditis, active rheumatic process at discharge, recurrences, absence of year-round prophylaxis allow prognostication of valvular heart disease. The majority of the factors promoting valvular and circulatory disorders also contribute to the onset of psychic abnormalities, astheno-organic syndrome, in particular.

The effects of carbamazepine and valproic acid on disturbances of behaviour, elimination of ethanol, acetaldehyde from the blood, the contents of adrenaline, noradrenaline, dopamine, serotonin, 5-hydroxyindoleacetic acid and histamine in the brain and blood in alcoholic postintoxication syndrome were studied on male albino rats. Carbamazepine and valproic acid were shown to reduce the behavioural manifestations of the syndrome, to increase elimination of ethanol and acetaldehyde, to normalize the levels of the mediators in the brain tissues, particularly in the thalamus.