[Prevalence of ischemic heart disease depending on factors of psychoemotional stress among men of mature age (epidemiological study)].

AIM: To establish associations of the prevalence of ischemic heart disease (IHD) and factors of psychoemotional stress in men of the open urban population in the age group 4564 years after two decades of life. MATERIALS AND METHODS: A cross-sectional epidemiological study using a model of the city of Tyumen was conducted on a representative sample of the population among males of mature age (4564 years). Based on standard epidemiological methods, IHD was established according to strict epidemiological criteria definite IHD. The study of the factors of psycho-emotional stress (depression, hostility, life exhaustion) was carried out according to the algorithms of the World Health Organization program MONICA-psychosocial. When calculating the odds ratio for the development of IHD, a low level of psycho-emotional stress factors was regarded as the absence of a sign, a combination of medium and high levels as a presence. RESULTS: The prevalence of ischemic heart disease in the open population (on the model of Tyumen) according to strict epidemiological criteria in men aged 4554 years was 8.2%, at the age of 5564 years 19.2%, a predominance of painless form of ischemic heart disease was revealed. According to the levels of factors of psychoemotional stress in mature men, mainly the average level of depression and life exhaustion, a high level of hostility were established. In men of an open population (on the model of Tyumen), depending on the psychoemotional stress, a high risk of developing a certain coronary heart disease was established in the age categories 4554 and 5564 years old in the presence of depression, at the age of 5564 years in the presence of hostility or life exhaustion. CONCLUSION: Consequently, the data obtained indicate the importance of further studying the factors of psychoemotional stress in men of mature age in Siberian populations, their relationships with conventional risk factors for coronary artery disease, as well as the advisability of preventive measures aimed at weakening the influence of not only conventional risk factors, but also factors of psycho-emotional stress. among the Russian population.

[MENTAL DERANGEMENT AS A MANDATORY MEDICAL CRITERION OF LIMITED SANTY].

The aim of the article is scientific conceptualization of the problem of mental derangement as a mandatory medical criterion of limited sanity according to criminal legislation by experience of Ukraine and some foreign countries and development of new approaches to such status assessment. Empirical study base of the problem consists of judgments of conviction taken from Unified State Register of Court Rulings of Ukraine and carried out on persons who commit crimes in the state of limited sanity from March 1st, 2014, till August 1st, 2020. Results of some foreign researchers' studies of the problem in question have been used as well. A combination of general and special scientific methods (comparative method, system structural method, method of statistical analysis, method of legal phenomenon system analysis etc.) has been applied to reach the aim in view. In conclusion: medical criterion of limited sanity ("mental derangement") used by lawmaker does not allow defining clearly types of illnesses, represent all possible types of psychiatric pathology and also causes complications in law enforcement practice. It has been proved that increase of quantity of people having mental derangements and quantity of crimes committed by such people shows that non-application of compulsory measures of medical care, correlational programs leads to repeated crimes commitment. Taking into account absence of duration of compulsory measures of medical care application, it has been suggested to stipulate this by Ukrainian legislation and to develop classification of mental derangements and criteria of their division into severe and non-severe.

Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial.

BACKGROUND: Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3%-4% of non-small-cell lung cancer (NSCLC) and is associated with unfavorable prognosis. While MET is a validated drug target in lung cancer, the best biomarker strategy for the enrichment of a susceptible patient population still remains to be defined. Towards this end we analyze here primary data from a phase I dose expansion study of the MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC. PATIENTS AND METHODS: Eligible patients [≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2] with MET-dysregulated advanced NSCLC, defined as either (i) MET status by immunohistochemistry (MET IHC) 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2.0 or gene copy number (GCN) ≥5, or (ii) epidermal growth factor receptor wild-type (EGFRwt) and centrally assessed MET IHC 3+, received capmatinib at the recommended dose of 400 mg (tablets) or 600 mg (capsules) b.i.d. The primary objective was to determine safety and tolerability; the key secondary objective was to explore antitumor activity. The exploratory end point was the correlation of clinical activity with different biomarker formats. RESULTS: Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received two or more prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69.1%). The median treatment duration was 10.4 weeks. The overall response rate per RECIST was 20% (95% confidence interval, 10.4-33.0). In patients with MET GCN ≥6 (n = 15), the overall response rate by both the investigator and central assessments was 47%. The median progression-free survival per investigator for patients with MET GCN ≥6 was 9.3 months (95% confidence interval, 3.8-11.9). Tumor responses were observed in all four patients with METex14. The most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%). CONCLUSIONS: MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC (NCT01324479).

The Influence of the Cholesterol Level in Cells on Endovanilloid Cytotoxicity.

The influence of the cellular cholesterol content on the cytotoxicity of endovanilloids acyldopamines was studied in MDA-MB-231 and MCF 10A cells. The activity of acyldopamines depends on the cellular cholesterol content, and a decrease in cholesterol content increases the cytotoxicity of acyldopamines.

Neuroprotective and Antioxidant Activity of Arachidonoyl Choline, Its Bis-Quaternized Analogues and Other Acylcholines.

The antioxidant activity and protective effect in the toxicity model of H2O2 were studied for arachidonic (AA-CHOL), docosahexaenoic (DHA-CHOL), linoleic (Ln-CHOL), and oleic (Ol-CHOL) fatty acids, as well as arachidonoyl dicholine (AA-diCHOL) and O-arachidonoyl bistetramethylaminoisopropanol (ABTAP). AA-CHOL, DHA-CHOL and Ln-CHOL provided a 20% increase in cell survival. AA-CHOL, AA-diCHOL, Ol-CHOL, and ABTAP had a radical-scavenging effect in the ABTS test, approximately equal to the activity of a standard radical scavenger Trolox.

[New breeding and technological evaluation criteria for fruit and berry products for the healthy and dietary food industry].

For the formation of a healthy diet, it is important to provide an economic and physical availability of the assortment of importsubstituting high quality and safe horticultural products, and to improve the industrial assortment. Wherein, the traits which define the consumer demand, such as quality and the chemical composition of fruits, saturation with essential micronutrients for healthy and dietary nutrition, should be taken into account in the first place among other breeding criteria, such as an early maturity and productivity. The aim of the research was the determination of breeding and technological priorities for fruits and berries from the point of view of the content of macro- and micronutrients for the development of dietary foodstuffs. Material and methods. The object of the investigation was the data on the content of protein, total sugar, mono- and disaccharides, sodium, potassium, calcium, magnesium, iron, copper, zinc, organic acids, polyphenolic compounds, flavonoids, anthocyanins, hydroxycinnamic acids, resveratrol, piceid, vitamins С, E, B1, B2, PP and carotenoids in samples of fruit and berry crops grown on the experimental production sites of the Federal Research Center named after I.V. Michurin (25 varieties of apple, 21 varieties of pear, 14 - of cherry, 5 - apricot, 10 - honeysuckle, 14 - strawberry, 8 forms of viburnum, 18 varieties of raspberry, 13 varieties of gooseberry, 10 forms of sea buckthorn, 12 varieties of plum, 8 varieties of red currant, 12 varieties of black currant). The statistical software package Statistica 6 was used for statistical data processing and construction of mathematical models. Results and discussion. The scale of priority distribution was developed, based on the analysis of the micronutrient composition of fruit and berries. The limits of low, medium and high micronutrient content in horticultural products were defined. Therefore, the threshold values of high level (3 points) were determined as ≥6 g/100 g for the dietary fiber and ≥30% of the recommended daily intake for the biologically active substances (BAS), minerals and trace elements. The threshold values of medium level of content (2 points) were determined as ≥3 g/100 g for the dietary fiber, ≥15% of the recommended daily intake for the BAS, minerals and trace elements. And threshold values of low level of content (1 points) were determined as values of indicators which are less than aforementioned. It was found that the categories of low priority (1 point) in the studied crops include protein, vitamins B1 (except for honeysuckle), B2, E (except for sea buckthorn) and PP, as well as sodium, calcium and zinc. The majority of the research objects has medium values as a source of soluble dietary fiber, carotenoids, flavonoids, hydroxycinnamic acids and potassium. The content of ascorbic acid and polyphenolic compounds, including anthocyanidins demonstrates the highest priority among the studied crops (3 points). According to the data obtained, the most of cultivars has a high content of organic acids (citric and malic), and more than 45.0% of the cultivars have a high content of vitamin C. 55.8% of cultivars have a high content of polyphenolic compounds, while 23.4% of cultivars are the sources of polyphenolic compounds too. Also 45.8% of cultivars have a high content of anthocyanidins, 25.0% of cultivars have a high content of flavonoids and hydroxycinnamic acids, 2.9% of cultivars are rich in iron. 62.0% of cultivars are the sources of soluble dietary fiber, 49.6% - sources of flavonoids, 13.0% - sources of potassium, 5.8% - sources of magnesium, 2.9% - sources of copper. Conclusion. The assessment of the chemical composition of fruits and berries from the standpoint of the presence and the content of macro- and micronutrients and BAS, proposed as a breeding program priority for the development of foodstuffs for specialized, dietary and therapeutic nutrition, is the basis for the future work on identification of complex sources, formation of unique food matrices, and selection of technological processes to develope a line of specialized foodstuffs.

[Biological value of fruits and berries of Russian production].

Fruits and berries are the most important sources of a wide range of biologically active substances, including vitamin C, carotenoids, flavonoids, anthocyanins. In order to replenish and update data on the content of food and biologically active substances in the tables of the chemical composition of food products, a study of the content of mono- and disaccharides, dietary fiber was carried out; vitamins C, B1, B2 and E, minerals and trace elements; flavonoids (in terms of rutin), anthocyanins; organic and hydroxycinnamic acids, stilbenoids in various varieties of 16 fruit and berry crops. Material and methods. The material for the study was the fruits of promising varieties and selected forms of pome fruit (apple, pear), stone fruit (cherry, plum, apricot), berry (garden strawberry, raspberry, black currant, red currant, gooseberry), non-traditional crops (actinidia, honeysuckle, cornelian cherry, viburnum, sea buckthorn, rosehip) - a total of 208 samples grown at the I.V. Michurin Federal Scientific Center. The B vitamins were determined by the fluorometric method, and vitamin E, organic and hydroxycinnamic acids, carbohydrates, and stilbenoids were determined by HPLC. The amount of anthocyanin pigments was determined by pH differential spectrophotometry, dietary fiber - by enzymatic-gravimetric method, flavonoids - spectrophotometrically. Results and discussion. The main carbohydrate of apricot is sucrose, black currants, cherries, raspberries and honeysuckle contain mainly fructose and glucose. Raspberries and currants are high in fiber. Comparison of the obtained data on the content of vitamins B1, B2, E, flavonoids and anthocyanins in the studied population of varieties in comparison with the published data of tables of the chemical composition of food products in the USA and Russia was carried out. By the content of vitamin C in descending order, the fruits are arranged in a row: black currant > sea buckthorn > honeysuckle > strawberry > red currant > viburnum > gooseberry > raspberry > apple. Berries, making a significant contribution to providing the body with vitamin C, are not an essential source of vitamins B and E. The inclusion of 100 g of fresh fruit in the diet provides about 10% of the recommended dietary intake for potassium (apricot, gooseberry, cherry and black currant), magnesium (apple, cherry, strawberry) and dietary fiber. Honeysuckle and black currant are high in anthocyanins; consumption of 100 g of these berries will ensure adequate intake of these micronutrients. Some varieties of strawberries, apples and pears are rich in hydroxycinnamic acids. The data obtained can be used to refine the indicators in the existing tables of the chemical composition of food products. Conclusion. The obtained data on the composition of fruit and berry products will make it possible to more correctly calculate the nutritional value of rations using questionnaire-survey methods. Combined analysis of the composition of biologically active substances in berries and fruits makes it possible to more reasonably make the choice of a particular product in the dietary correction of the ration of healthy and sick people.

Neuroprotective Action of Amidic Neurolipins in Models of Neurotoxicity on the Culture of Human Neural-Like Cells SH-SY5Y.

It was established that in neurodegeneration models in the human neuron-like cell line SH-SY5Y, amide derivatives of arachidonic and docosahexaenoic acids were inactive in experiments with MPP+ and CoCl2 but protected from H2O2. The protective activity of neurolipins decreased in the series DHA-DA > AA-SER ≥ AA-GLY > AA-GABA ≥ AA-EA and was manifested starting from a concentration of 0.5 nM.

Levels of depression and life exhaustion in the open population of the middle urbanized Siberian city: gender differences.

AIM: The aim of the study was to determine the levels of depression and life exhaustion in men and women of the open urban population in the age range. MATERIALS AND METHODS: A single-stage epidemiological study was conducted among people of both sexes aged 25-64 in Tyumen. A representative sample was formed from the electoral lists of citizens by the method of "random numbers" - 2000 men and women with a response among men 85.0%, among women - 70.3%. The study of depression was conducted according to the algorithms of the program of the world health organization "MONICA-psychosocial". RESULTS: The prevalence of depression in the Tyumen population and in the age and sex groups showed a predominance of the average level over the high, in the age categories 25-34 and 35-44 years - significantly higher prevalence of high levels of depression in women. The higher prevalence of the average level of men and women IN the open population was determined to be relatively high. The average level of LIFE significantly prevails in women in the older age categories and in the population as a whole, the high level of LIFE - at the age of 25-34 years in women and at the age of 55-64 years in men. CONCLUSION: Therefore, in the open population of the middle-urbanized Siberian city there is a need to form an integrated approach to the prevention of non-infectious diseases, especially cardiovascular diseases, as it is established that prevention programs lead to a reduction in the burden of depression and, and effective approaches to the prevention of psycho-emotional States at the level of individual communities include school-oriented programs to teach positive thinking among the population, starting from a young age.

[The study of the polyphenolic complex and iridoid glycosides in various cultivars of edible honeysuckle fruits Lonicera edulis Turcz. ex Freyn].

The high content of minor biologically active substances in the fruits of wild-growing and cultivated varieties of honeysuckle, along with the low knowledge of the chemical composition of domestic varieties, determines the relevance of the study of their qualitative and quantitative composition. The aim of the work was to study the detailed composition of the main groups of biologically active polyphenolic compounds [anthocyanins, flavonoids, hydroxycinnamic acids (HCAs), proanthocyanidins] and iridoids in various cultivars of domestic edible honeysuckle fruits (Lonicera edulis Turcz. Ex Freyn). Material and methods. 15 samples of frozen fruits of edible honeysuckle harvested in Tambov, Voronezh, Moscow regions and Karelia were investigated. The total content of polyphenolic compounds (in terms of gallic acid equivalents) was determined by the modified Folin-Ciocalteu method, the total content of monomeric anthocyanins (in terms of cyanidin-3-glucoside) - by pH-differential spectrophotometry, proanthocyanidins (in terms of procyanidin B2) - by the modified Bate-Smith method. The profiles of individual anthocyanins, iridoids, flavonoids and HCAs was determined by HPLC-DAD/TOF-MS. The carbohydrate profile by capillary electrophoresis and antiradical activity in DPPH test in vitro were investigated as well. Results and discussion. The main groups of polyphenolic compounds were anthocyanins and proanthocyanidins. Cyanidin-3-glucoside was found as predominant among anthocyanins (>85% of their sum). Substantial amounts of iridoids (from 78.0 till 341.8 mg/100 g) were found in the honeysuckle examined. The loganic acid and loganine prevailed among iridoids. The total content of flavonoids varied in the range of 9.2- 46.6 mg/100 g, the main of which was rutin. Among HCAs chlorogenic acid prevailed, which accounted for 85.7-90.4% of the total amount of HCAs (45.9-79.8 mg/100 g). A correlation was found between the amount of polyphenolic compounds and the antiradical properties of honeysuckle fruits in DPPH test. Conclusion. Based on the results of the study the most promising varieties of domestic honeysuckle in terms of the highest content of polyphenolic antioxidants and iridoids with potential anti-inflammatory, hypoglycemic, hypolipidemic, antimicrobial and other types of biological activity were determined for the first time.

[Nutrient value of fruit in promising strawberry varieties].

One of the current areas in research of fruit and berry crops is the study of their nutritional value and micronutrient composition. Valuable chemical composition of the strawberry determines a wide spectrum of its utilization not only as fresh fruit, but also as a raw material for food industry. Breeding requirements for contemporary strawberry varieties together with yield, large-fruit, important taste and dietary qualities of fruit provide for higher content of biologic active substances. The aim of the research was an integrated assessment of strawberry fruit for content of nutrients and bioactive compounds, as well as mineral elements, and its antioxidant activity. Material and methods. The objects of investigation were berries of 5 strawberry varieties bred in the I.V. Michurin Scientific Centre (Lakomaya, Prazdnichnaya, Privlekatelnaya, Urozhaynaya CGL, Feyerverk) and 9 foreign varieties (Vima Zanta, Dukat, Zefir, Kama, Maryshka, Red Gauntlet, Festivalnaya romashka, Honey, Elsanta) which are promising for cultivation in the Black Soil Region of Russia. The content of soluble solids was determined by the refractometric method, sugars - by Bertrand's method, pectins - by the volumetric method, anthocyanins - by pH-differential spectrophotometry. Total content of antioxidants was defined by amperometric method with recalculation per quercetin. Determination of vitamin B1 was carried out using the fluorometric thiochrome method, vitamin B2 - by fluorometric titration with riboflavin-binding apoprotein after acid-enzymatic hydrolysis, ascorbic acid, vitamin E (tocopherols), niacin, organic and hydroxycinnamic acids - by HPLC, flavonols - spectrophotometrically, minerals and trace elements - by atomic absorption method. Results and discussion. A significant variation in the chemical composition indices depending on the varietal characteristics was found. Strawberry fruit accumulated 8.5-12.0% soluble solids, 5.9-8.7% sugars, 1.5-2.1% of fibre, 0.78-1.12% pectin substances, 0.89-1.45% organic acid; 100 g contain 33.5-48.2 mg vitamin C, 18.3-108.5 mg anthocyanins, 0.024-0.041 mg vitamin B1, 0.012-0.029 mg vitamin B2, 0.10-0.26 mg niacin, 0.26-0.60 mg TE vitamin E, 102-270 mg potassium, 0.15-0.95 mg iron; total antioxidant activity ranged within 180.8-350.0 mg/100 g. High level of anthocyan accumulation (over 80.0 mg/100 g) was observed in Privlekatelnaya, Lakomaya and Feyerverk strawberry varieties. Urozhaynaya CGL, Privlekatelnaya and Lakomaya varieties were characterized by dessert taste. According to the results of the studies Privlekatelnaya variety stood out because of the high complex accumulation of vitamin C, anthocyanins, and high total antioxidant activity. These varieties are recommended for both fresh use and for freezing, as well as for production of functional foods. Conclusion. The obtained data are of interest for further inclusion in the Tables of the chemical composition of Russian food products.

Stress in the family - association with prevalence of cardiovascular diseases in men of the open city population.

AIM: The aim of the study was to establish associations of the prevalence of coronary artery disease (CAD), metabolic syndrome (MS) and arterial hypertension (AH) with family stress in open male population of Tyumen aged 25-64 years. MATERIALS AND METHODS: Cross-sectional epidemiological survey was conducted on representative sample of 1000 individuals (250 in every 4 decades: 25-34, 35-44, 45-54, 55-64 years) formed from the election list of males in one of the administrative districts of Tyumen. The response to cardiac screening was 85.0% - 850 patients. Different types of CAD were defined based on standard methods in epidemiological surveys. "Certain" CAD and "possible" CAD were determined according to extended epidemiological criteria. IDF criteria (2005) were used for the MS assessment, AH was considered as a component of the MS. A questionnaire of WHO MONICA «Knowledge and attitude to health¼ was used to analyze stress in families. RESULTS: The results of the study showed that more than 80% of males in open urban population, mostly older individuals, had a stable marital status last twelve months, while one-third of the male population had conflicts in their families and the fifth part did not have the opportunity to relax at home. Male patients with CAD had family stress more frequently during last 12 months on extended epidemiological criteria. In the open male population aged 25-64 years with MS and AH there was found more stable marital status versus comparison groups. CONCLUSION: Standardized methods and the accumulated database should be used to continue objective monitoring of the epidemiological situation of cardiovascular diseases and psychosocial risk factors in open urban population during regional preventive program.

[Consumption of carbohydratecontaining beverages and their contribution to the total calorie content of the diet].

The article presents data on the frequency of consumption of carbohydrate-containing sweet carbonated drinks by the population of the Russian Federation and their contribution to the overall caloric intake of the diet. Questioning 11 850 people of different ages (from 12 to 60 years) and sex in all eight Federal Districts of Russia has been conducted. The frequency of food consumption has been studied, and in parallel dietary intake has been assessed using 24-hour recall method. The survey showed a fairly low frequency of consumption of sweet carbonated beverages and no significant differences in the frequency of their consumption by the population of various federal districts of Russia. With a certain frequency from 55.5 to 67.3% of the population consumed sweet carbonated drinks, while 18.1-20.9% of the respondents did not consume them more often 1-3 times a month, and 1.3% of the surveyed (from 0.3% in the North- West to 3.9% in the Southern Federal District) - 2 times a day or more often. Analysis of the data obtained showed that the contribution of the carbohydrate component contained in sweet carbonated beverages, even when consumed frequently (5-6 times a week) did not exceed 3.71% of the total diet calorie intake and not more than 7.1% of the caloric value of carbohydrates' intake.

N-acyl dopamines induce apoptosis in PC12 cell line via the GPR55 receptor activation.

Dopamine amides of arachidonic, docosahexaenoic, and oleic acids were found to induce apoptosis in PC12 cells, which was blocked exclusively by antagonists and preincubation agonists of the receptor GPR55, belonging to the group of non-CB1/CB2 receptors.

Synthesis of N-acyl derivatives of Pro-Gly-Pro-Leu peptide: Proteolytic stability in vitro and effects on mouse macrophage cells RAW264.7.

Acetyl, oleoyl, arachidonoyl, and docosahexaenoyl derivatives of the Pro-Gly-Pro-Leu peptide with a chemical purity of 99.8% were synthesized. The degradation kinetics of the Pro-Gly-Pro-Leu derivatives under the action of leucine aminopeptidase, nasal mucus, and microsomal fraction of the brain and blood of rats was studied. It was shown that the N-acyl derivatives of Pro-Gly-Pro-Leu proved to be more resistant to the action of leucine aminopeptidase and other enzyme systems. The study of the cytotoxic and anti-inflammatory activity of preparations on the mouse macrophage cell line RAW264.7 showed that acylation with oleic and arachidonic acid makes the peptide cytotoxic with LC50 in the range of 70-15 µM and gives it anti-inflammatory properties with EC50 of 32 and 36 µM, respectively.

[Associations between high levels of hostility and coronary heart disease in an open urban population among 25-64-year-old men]. / Assotsiatsii vysokogo urovnia vrazhdebnosti i ishemicheskoi bolezni serdtsa v otkrytoi gorodskoi populiatsii sredi muzhchin 25­64 let.

AIM: To establish the associations of the prevalence of coronary heart disease (CHD) with high levels of hostility in the open population of 25-64-year-old men in an average urbanized Siberian town. SUBJECTS AND METHODS: A cross-sectional epidemiological survey was conducted in a representative sample of the electorate of a Tyumen administrative district among 1000 males, with 250 being in each of 4 life decades (25-34, 35-44, 45-54, and 55-64 years). There were 850 (85%) responses. Different forms of CHD were identified by standard methods (the WHO exertional angina questionnaire, resting EEG, and Minnesota coding) used in epidemiological surveys. Definite CHD (DCHD) and possible CHD were identified. A continuous survey method was used by self-filling out the WHO MONICA-psychosocial questionnaire to estimate the levels of hostility. RESULTS: In an average urbanized Siberian town, the prevalence of high levels of hostility among 25-64-year-old men was 46.4% (age-adjusted rate). The high levels of hostility increased with age, peaking in the 55-64-year-old group. In the Tyumen male population aged 25-64-year-old, the odds ratio (OR) for coronary heart disease and high levels of hostility was 2.71; 95% confidence interval (CI), 1.63-4.52 (p<0.05); that for DCHD was almost twice higher (OR, 4.65; 95% CI, 2.14-10.12 (p<0.05). In the older men aged 55-64 years, OR for coronary heart disease and high levels of hostility was 5.42; 95% CI, 2.32-12.66 (p<0.05); that for DCHD was 25.85; 95% CI, 3.30-202.60 (p<0.05). CONCLUSION: Consequently, the epidemiological criteria for psychosocial risk factors, including hostility, which are detected by the standardized survey methods, should be used in prophylactic examinations of a male population and in the selection of able-bodied people with cardiovascular disease to be comprehensively examined and followed up.

N-acyl dopamines induce cell death in PC12 cell line via induction of nitric oxide generation and oxidative stress.

It was shown that dopamine amides of arachidonic, oleic, and docosahexaenoic acids exhibit toxicity with respect to PC12 pheochromocytoma cell line. The mechanism of realization of the cytotoxic effect of acyl dopamines is the induction of oxidative stress. This event is preceded by triggering the synthesis of nitric oxide.

[Expansion of the range of anthocyanin food colorants from unconventional vegetal primary products].

The purpose of work to study the content of anthocyanins and other biologically active substances in residues of fruits of Sanberri from receivingjuice and mash. It is established that residues contained over 70% solids, more than 60% of dietary fiber, to 55.4 mg/% of ascorbic acid and up to 90.0 mg/% of anthocyanins. Furthermore, they possessed high antioxidant activity (156.8-399.4 mg/% dihydroquercetin equivalent) that allowed to recommend them as raw materials for receiving natural food colorants. The concentrated food dye from Sanberri's residue (50-51% soluble solids) had intensive color varying from dark-violet (at acidity of 1.0%) to claret-red (at acidity of 3.0%), possessed high antioxidant activity (1308.2-2223.5 mg/%) and contained a large amount of anthocyanins (666-976 mg/%).

A first-in-human phase I, dose-escalation, multicentre study of HSP990 administered orally in adult patients with advanced solid malignancies.

BACKGROUND: Heat-shock protein 990 (HSP990) is a potent and selective synthetic small-molecule HSP90 inhibitor. The primary objectives of this phase I first-in-human study were to determine dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included characterisation of the safety profile, pharmacokinetics (PKs) and pharmacodynamics (PDs). METHODS: Heat-shock protein 990 was administered orally once or two times weekly on a 28-day cycle schedule in patients with advanced solid tumours. Dose escalation was guided by a Bayesian logistic regression model with overdose control. RESULTS: A total of 64 patients were enrolled. Fifty-three patients received HSP990 once weekly at 2.5, 5, 10, 20, 30, 50 or 60 mg, whereas 11 patients received HSP990 two times weekly at 25 mg. Median duration of exposure was 8 weeks (range 1-116 weeks) and 12 patients remained on treatment for >16 weeks. Dose-limiting toxicities occurred in seven patients and included diarrhoea, QTc prolongation, ALT/AST elevations and central neurological toxicities. The most common drug-related adverse events were diarrhoea, fatigue and decreased appetite. Further dose escalation beyond 60 mg once weekly was not possible owing to neurological toxicity. Rapid absorption, no drug accumulation and large interpatient variability in PK exposures were observed. No objective responses were seen; 25 patients had a best overall response of stable disease. CONCLUSIONS: Heat-shock protein 990 is relatively well tolerated, with neurological toxicity being the most relevant DLT. The single agent MTD/RP2D of HSP990 was declared at 50 mg once weekly.

[The optimization of the nitric oxide quantitative analysis for its determination in the cultural medium of mammalian cell culture].

The protocol for the quantitative analysis of nitric oxide as nitrite-ion suitable for determination of its production by a mammalian cell culture was developed. The optimal results were obtained using microvolume-adjusted Griess method after the preliminary reduction of NO3- to NO2- with non-activated cadmium. The protocol was verified on a rat glioma C6 cell culture. The developed method may be used for the nitric oxide determination in 96-well and 48-well microplates; the detection limit is 2.1 ± 0.1 µM for NO2- and 2.9 ± 0.1 µM for NO3-.