Options for the Spatial Development of Russia in the Context of Interregional Interactions.

The article develops an approach to building a model of interregional interactions based on regionalization of national input-output tables. Options for the spatial structure of gross output depending on the forecast of investments in fixed assets are presented. Five main options for the prospective spatial organization of economic development are proposed. The advantages of the scenario of locally diversified growth, which is more acceptable from the point of view of territorial justice but requiring active state regulation of spatial development, are shown.

Behavioral and Hemodynamic Effects of Free and Protein-Bound Angiotensin IV in Rats in Experimental Hypo- and Hyperglycemia: Comparative Aspects.

In rats with acute hypo- and hyperglycemia the initial effects of free angiotensin IV and its complexes with functionally different carrier proteins (transport protein BSA, neuron-specific protein S100b) on hemodynamics and behavior of rats were qualitatively altered, in comparison with those in intact animals. At the same time, free angiotensin IV under conditions of hypo- and hyperglycemia paradoxically acquired functions of angiotensin II (moderate hypertension, tachycardia, polydipsia and activation of instrumental drinking behavior). Concurrently, complexes of angiotensin IV with BSA and S100b acquired functions of free angiotensin IV (hypotensia, suppression of drinking behavior). It is suggested that complexes of angiotensin IV with functionally different proteins are involved in a differentiated way first in compensation of behavior and hemodynamics impairment produced by acute and/or chronic hypo- and hyperglycemia, and then in qualitative transformation of these adaptive processes into stable pathological condition involving mechanisms of so called "metabolic memory".

Comparative study of the effects of free bound and carrier protein angiotensin II in experimental hypoglycemia and hyperglycemia.

Experimental hypoglycemia and hyperglycemia eliminated the differences in the regulatory functions of free angiotensin II and its complexes with carrier proteins (transport protein BSA and neurospecific protein S100b) in rats. Under these conditions, free and protein-bound angiotensin II primarily suppressed operant drinking behavior and reduced the hypertensive and tachyarrhythmic effects in comparison with control rats. These changes were most pronounced during acute hyperglycemia. We hypothesized that complexes of angiotensin II with functionally different proteins are differentially and simultaneously involved in not only compensation of behavioral and hemodynamic disturbances during acute and/or chronic hypoglycemia and hyperglycemia, but also their transformation into pathological processes mediated by the so-called metabolic memory mechanisms.

[Estimation of atherogenic immune complexes containing modified lipoproteins in complement fixation tests].

A method for determining atherogenicity of the immune complexes containing multiple modified low-density lipoprotein (mmLDL) in complement fixation test has been found. In the proposed method, the precipitate immune complexes containing mmLDL (IC mmLDL) was prepared from human serum by treating it with buffer (8.3% of th PEG 3350 and 3.3% PVP 12600 th in the ratio 1: 1.2) for 10 min at 23 °C. IC mmLDL aggregates were separated by centrifugation at 3100g for 10 min at 23 °C. The precipitate IC mmLDL was dissolved in buffer without PEG and PVP, cholesterol content and the degree of binding of guinea pig complement were measured. Atherogenicity of the IC mmLDL was registered as the ratio of the degree of complement binding to cholesterol in the the immune complexes.

Heart rate variability during "alarm stage" of burnout syndrome in emergency doctors.

The parameters of heart rate variations were examined in emergency care doctors that demonstrated the initial signs of defensive psychological burnout syndrome related to their professional activity. These parameters were compared within each of two groups with different individual typological features. The differences in the heart rate variability parameters were revealed between the examinees that were at the compensation or alarm stages of the burnout syndrome.

Free and protein-bound angiotensin II(1-7)in the regulation of drinking behavior and hemodynamics in rats.

We compared physiological activity of synthetic analogues of endogenous protein-peptide compounds, complexes of angiotensin II(1-7)with functionally different proteins (transport protein, serum albumin; and neurospecific Ca(2+)-binding protein, S100b). Physiological activity of angiotensin II(1-7)was shown to depend on the type of a carrier protein. Our results suggest that complexes of angiotensins with BSA and S100b are strong factors for the integration of central and peripheral functions at the homeostatic and behavioral level.

Modification of normal activities of angiotensin II and angiotensin IV in rats with experimental hypo- and hyperglycemia.

Changes in blood glucose levels are paralleled by modification of normal activities of angiotensin II and angiotensin IV. Hypo- and hyperglycemia similarly reduced the hypertensive effect of angiotensin II and similarly distorted the initial hypotensive effect of angiotensin IV. Presumably, the adaptation and compensatory processes in the renin-angiotensin system under conditions of shifted homeostatic constants manifest by phenomena of external reintegration and redistribution of functions of its individual peptide components. This provides restructuring of the mechanisms of intra- and intersystemic organization of physiological functions under extreme conditions.

[Immune links in the system organization of behaviour].

The work is devoted to the research of immune mechanisms in self-control of various functional systems of homeostatic and behavioral levels. Distinction of immune mechanisms in rats with different prognostic stress-resistance is established. Immunization of rats by conjugates of various neuromediators with bovine serum albumin selectively changes the animals stress-resistance. Participation cytokines in reactions of a brain's separate neurons and their interaction with a leading neuromediator - norepinephrine is established. Individual changes of pro- and anti-inflammatory cytokines in blood serum are shown in rats with different stress-resistance. There are revealed features of morphological distinctions of immunogenic structures small intestine fabrics in animals with various behavioral activity in the "Open field" test.

Regulation of hemodynamic parameters under conditions of systemic administration of angiotensin II and angiotensin IV to rats after carotid glomectomy.

Systemic administration of angiotensin II was followed by an increase in systolic BP and HR in rats with carotid glomectomy, the time of attaining maximum values in treated animals was much higher than in sham-operated controls. Injection of angiotensin IV slightly reduced systolic BP in sham-operated animals and increased it in rats with carotid glomectomy. The involvement of the local renin-angiotensin system of the carotid body in systemic mechanisms of hemodynamics regulation is discussed.

[Diabetes mellitus and obesity: projection onto oncological morbidity].

Peculiar features of human morbidity and their changes in time are registered chronologically starting from the XVII-VYIIIth centuries. After the period of predominantly infectious diseases, chronic and non-communicable conditions continued to gain momentum in the last 3-5 decades. Side by side with AIDS, accidents, effects of smoking etc, the global epidemics of diabetes mellitus and obesity comes up to take a leading place in the general population morbidity. In this communication, possible causes of this situation and its possible association with cancer are considered based on the results of original studies. Measures for the prevention and treatment of these diseases are discussed.

Complexes of angiotensin IV with functionally different proteins in the regulation of drinking behavior and hemodynamics in rats.

We compared physiological activity of synthetic complexes from angiotensin IV and functionally different proteins (transport protein, bovine serum albumin; and neurospecific Ca(2+)-binding protein, S100b) as model analogues of endogenous protein-peptide complexes. Physiological activity of angiotensin IV was specifically modified by these proteins. Our results suggest that complexes of angiotensin IV with bovine serum albumin and S100b are strong factors for the integration of central and peripheral functions at the homeostatic and behavioral level.

[The dual (joker) function of glucose: study of its association with aging and glucose metabolism disorders].

Relation was studied between generation of glucose-induced reactive oxygen species (ROS), which appear to be related to DNA damage (genotoxic effect, G), and insulin secretion (endocrine or hormonal effect, H) in women of different ages (one group under 45 and the other one over 45; n=25 and n=14, respectively). The healthy women in those two groups were compared with patients in whom we had found an impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) (n=17, mean age 57.3 +/- 2.7). The hormonal effect of glucose was more pronounced in the senior group, and especially in group with IGT, if compared with the younger group. Genotoxic effect of glucose was discovered more frequently in the younger group, mainly in smoking women. Comparison of G/H effects showed that the evaluation of glucose-induced genotoxity (GIGT) was more frequent in the IGT group than in the senior group (p < 0.05). No difference was detected in the GIGT frequency values in the two healthy groups. It may therefore be concluded that GIGT did not increase within the ambit of ageing studied in this work, while it increased in the IGT group. It is possible that the high frequency of the G effect in the IGT group could be a marker of oxidative stress and/or predisposition to complications in DM. The dual (joker) function of glucose and the prevalence of G effects over H effects may be of use in choosing the method of correction for each particular case.

[Progenotoxic shift in mammary adipose tissue (adipogenotoxicosis): association with clinical and biological characteristics of breast cancer].

The study is concerned with identification of a relationship between levels of production and accumulation of compounds capable of hormonal and progenotoxic effects in mammary fat, on the one hand, and characteristics of tumor tissue in breast cancer, on the other. Mammary fat was sampled at a distance of 1.5-2 cm from tumor edge (79 pts.). Case histories were used to provide data on clinical stage, size, grade and regional lymph node involvement. Levels were assayed of leptin, adiponectin, tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), thiobarbiturate-reactive products (TBRP) and DNA oxidative damage marker (8-OH-dG) from 4hr-incubates of fat tissue culture. Mammary fat aromatase was assayed by radiometrical means while macrophage-assisted fat infiltration (CD68) and estrogen-4-hydroxylase (CYP1B1) expression were evaluated immunohistochemically. Radio-competitive and immunohistochemical methods were used to assay estrogen (ER) and progesterone (PR) receptor levels in tumor and tumor-related expression of cytokeratins 5/6 ("basal") and 7/8 ("luminal" epithelium), respectively. As far as hormonal properties of mammary fat were concerned, there were direct correlations between aromatase concentration, on the one hand, and tumor stage and size, on the other, and adiponectin secretion and CK7 expression in tumor. Besides, an inverse correlation was found between mammary fat-mediated release of leptin and adiponectin, on the one hand, and stage and regional lymph node involvement, on the other. The following main relationships were identified by comparison of the clinico-biological characteristics of tumor and markers of proinflammatory/progenotoxic properties of mammary adipose tissue: tendency toward direct correlation with IL-6 and 8-OH-dG in fat (tumor progress stage); direct correlation with TNF-alpha secretion rate (malignancy grade); lymph node involvement--tendency toward direct correlation with NO generation; CK5 expression in tumor--tendency toward direct correlation with 8-OH-dG, TBRP and CD68 fat infiltration; CK7 expression in tumor--tendency toward inverse correlation with NO generation in adipose tissue; ER-negative phenotype of tumor--tendency toward higher generation of TBRP, NO and TNF/leptin in fat. Hence, shift toward predominance of proinflammatory/progenotoxic properties of mammary adipose tissue (adipogenotoxicosis) is associated with signs of less favorable course of tumor process in the mammary gland which calls for working out adequate measures.

[Endocrine-genotoxic switchings as promoter of main noninfectious diseases].

Peculiarities of the incidence and spread of main non-infectious diseases (MNID) are in one or another way connected with the conception of "normal" and "successful" aging. The age-related increase in the frequency of MNID, associated with estrogen deficiency or excess, can be explained by the presence of estrogen effect switching phenomenon. The increase in the genotoxic effect of estrogens, isolated or combined with the weakening of the hormonal effect, can worsen the clinical course of MNID (including malignant tumors of hormone-dependent tissues). The effects of two other endocrine-genotoxic switchings (the joker function of glucose and adipogenotoxicosis) may realize in the same direction. The three mentioned phenomena form the so called basic triad, separate elements of which can interact. Endocrine-genotoxic switchings and their inductors are targets for prophylactic measures and, possibly, therapeutic ones. Both approaches may be divided into several groups with different points of application, whereas their ultimate goal is optimal balance between hormonal and DNA-damaging effects of estrogens, glucose, and adipose tissue-associated factors.

Physiological effects of complexes of angiotensins with functionally different carrier proteins.

We compared activity of synthetic complexes of angiotensin II and functionally different proteins (transport protein, serum albumin and neurospecific Ca2+-binding protein S100b) as analogues of endogenous protein-peptide complexes. Physiological activity of angiotensin II was specifically modified by these proteins. It was hypothesized that the complex of angiotensin II and S100b is primarily involved in the regulation of hemodynamics, whereas the complex of angiotensin II and bovine serum albumin plays a role in the formation and realization of drinking behavior.

[Properties of mammary fat in breast cancer patients: topographic, systemic and environmental factors].

Breast cancer course may be influenced by a profile of steroids and peptides produced by mammary fat. The study was concerned with assessment of hormonal (leptin and adiponectin production, adipocyte diameter and aromatase level) and progenotoxic factors which characterize DNA damage (8-OHdG) and such cancer promoters as tumor necrosis (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), thiobarbiturate reactive products (TRP), macrophage/histiocyte infiltration, estrogen 4-hydroxylase expression (CYP1B1) in mammary fat located 1.5-2 cm or not less than 5 cm away from tumor edge. Thirty-three pairs of mammary fat samples from 23 menopausal and 10 cycling patients were used. Closer proximity of mammary fat involved intensified biosynthesis of estrogens (as shown by aromatase level) and their conversion to catechol derivatives (as shown by CYP1B1 concentration) as well as accumulation of 8-OH-dG. Smoking and hyperglycemic patients and those with considerable mammary fat volume revealed accumulations of anti-inflammatory and progenotoxic cytokines (IL-6 or TNF-alpha). Hence, hormonal/progenotoxic ratio in mammary fat can be identified both by topographic, systemic and environmental factors.

Effector peptides of the renin-angiotensin system in the central mechanisms of acquired and innate behavior in thirst in rats.

We report here a comparative analysis of the involvement of a number of components of the renin-angiotensin system in the performance of simple and complex forms of drinking behavior and thirst-associated non-drinking types of behavior. On central (intracerebroventricular) microinjection, [des-Asp1]-angiotensin I at doses equieffective to those of angiotensins II and III was found to be involved only in the performance of simple (taking water from the bowl) and linked forms of activity (comfort behavior, stress grooming, orientational-investigative, and feeding behavior). Angiotensin II was involved in the central mechanisms of complex acquired drinking behavior, selectively modulating its key stages (initial, final), while angiotensin III was involved only in the mechanisms of reproduction of the complex skill. All three substances induced "innate patterns of behavior" specific for each compound, these occurring at fixed periods of time after intracerebral microinjection. The effects of these substances were selectively suppressed by the AT1 receptor blocker losartan potassium.

[Hormonal and progenotoxic properties of mammary fat in pre- and postmenopausal cancer patients].

Since breast cancer may emerge both before and after menopause onset, relevant forms of the disease show marked biological and clinical differences. Intrinsic properties of mammary fat located in the vicinity of tumor, which play a definitive role in stromal-epithelial interactions, are an important factor of development of such differences. The DNA damage promoting hormonal (leptin and adiponectin production, aromatase activity) and progenotoxic. The properties of mammary fat such as formation of tumor necrosis factor, interleukin-6, nitric oxide, malonic aldehyde, macrophage/histiocyte infiltration and estrogen 4-hydroxylase expression, were studied in mammary fat tissue of 95 patients with receptor-positive or receptor-negative breast tumors (reproductive--25, menopausal--70). It was found that progenotoxic properties might somewhat predominate, as far as differences in parameters and pathways are concerned, both in menopausal and still cycling patients. Hence, progenotoxic damage which represents mammary fat tissue status is perhaps modified by a number of genetic and mitochondrial factors. It may exert unfavorable effect on the course of the disease within a fairly wide period.

[Effector peptides of the brain renin-angiotensin system in central mechanisms of learned and natural forms of drinking behavior in rats].

Central mechanisms of angiotensin involvement in initiation and realization of operant forms of drinking behavior were investigated. It was suggested that intracerebroventricular microinjection of angiotensin-II and angiotensin-IIl specifically affected the learned forms of drinking behavior. The experiments demonstrated that [des-Asp1]-angiotensin-I produced only the natural forms of drinking behavior. Angiotensins modulated specific forms of thirst-associated behavior such as exploring, grooming, and ingestive behavior. Injections of AT1 receptor antagonist losartan were associated with acute water intake decrease and sharp operant behavior inactivation.

Comparative analysis of dipsogenic effects of systemic and intracerebral injection of angiotensin II to rats after carotid glomectomy.

Systemic administration of angiotensin II after carotid glomectomy produced a less pronounced dipsogenic effects (consumption of water and NaCl solution) compared to sham-operated control animals. Injection of angiotensin II into the lateral cerebral ventricles of the same glomectomized rats increased water and NaCl consumption to a level surpassing that of sham-operated animals. The number of drinking acts and comfortable grooming acts decreased in glomectomized animals after systemic administration of angiotensin II, but increased after its intracerebral injection compared to the control. The results confirm the hypothesis that carotid chemoreceptors, as the peripheral component of the renin-angiotensin system, participate in the mechanisms of angiotensin-induced thirst, "salt appetite", and associated behavioral forms (comfortable grooming) synergically with the central cerebral receptors.