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One of the most outstanding scientific achievements in the thrombolysis is the development and administration of fibrinolysin - the first Soviet drug that lyses blood clots. Intracoronary administration of fibrinolysin reduced the mortality of patients with myocardial infarction by almost 20%. For his work in this field Yevgeny Chazov was awarded the Lenin Prize in 1982. Over the next decades, under his leadership, the Cardiology Center established scientific and clinical laboratories that created new generations of drugs based on fibrinolytics for treating patients with myocardial infarction, restoration of blood flow in ischemic tissue, and also studying the mechanisms of remodeling of blood vessels involving the fibrinolysis system. It have been found new mechanisms of regulation of the navigation of blood vessels and nerves growth, tumor growth and its metastasis with the participation of the fibrinolysis system proteins. The review reports the role of the fibrinolysis system in the thrombolysis, blood vessels growth and remodeling, neurogenesis, carcinogenesis and fibrosis. The article is dedicated to the 90th anniversary of academician E.I. Chazov.Одним из самых выдающихся научных достижений в области тромболизиса является разработка, создание и внедрение фибринолизина - первого советского препарата, разрушающего тромбы. Внутрикоронарное введение фибринолизина позволило снизить летальность больных инфарктом миокарда почти на 20%. За исследования в этой области в 1982 г. Евгений Иванович Чазов был удостоен Ленинской премии. В течение последующих десятилетий под его руководством в Кардиоцентре созданы научные и клинические лаборатории, в которых создавалось новое поколение препаратов на основе фибринолитиков для лечения больных инфарктом миокарда, восстановления кровоснабжения ишемизированной ткани, а также изучались механизмы ремоделирования кровеносных сосудов с участием системы фибринолиза. В результате научных исследований обнаружены новые механизмы регуляции направленного роста сосудов и нервов, роста опухоли и ее метастазирования с участием белков системы фибринолиза. В обзоре рассматривается современное представление о роли системы фибринолиза в разрушении тромба, роста и ремоделирования сосудов, нейрогенеза, канцерогенеза и фиброза. Статья посвящена 90-летию академика Е.И. Чазова.

Recently it has been found that the urokinase receptor (uPAR) and its ligands - urokinase (uPA) and SRPX2 protein play an important role in the development and functioning of the brain. There is a strong association between uPAR gene polymorphism and autism disorders in humans. Patients with autism, intractable lobe epilepsy, verbal dyspraxia and perisylvian polymicrogyria display significant changes in uPAR expression. Mice, lacking the uPAR gene develop epilepsy and demonstrate abnormal social behavior. uPA and SRPX2 protein, have been shown to be involved in pathological brain conditions such as autism, cognitive deficits and language disorders. Urokinase system that stimulates blood vessel growth as demonstrated before, also plays an important role in the regulation of the nerve growth via matrix remodeling and activation of neurotrophic and angiogenic factors. Moreover, the urokinase system also functions as a guidance system which determines the growth trajectory of the vessels' and nerves' in tissue regeneration. This review summarizes and integrates the results and recent progress in the field of uPAR and its endogenous ligands in brain development and cognitive functions.

Genetic diversity of 60 X-chromosome single nucleotide polymorphisms (XSNPid panel) in populations of Siberian Tatars and Tuvinians is described. A close spectrum of allele frequencies and a low level of their genetic differentiation (Gst = 0.021) is revealed. High discriminating power of the XSNPid panel in populations under study is demonstrated. The random matching probability (MP) of multilocus genotypes in males is 1.12 x 10⁻¹⁸ in Siberian Tatars and 7.77 x 10⁻¹⁶ in Tuvans. In females, MP is several orders of magnitude lower: 1.51 x 10⁻²⁵ in Siberian Tatars and 1.83 x 10⁻²³ in Tuvinians.

We for the first time have examined the autosomal gene pool of the Siberia, Central Asian and the Far East populations (27 populations of 12 ethnic groups) using a set of polymorphic Alu insertions in the human genome. The results of the analysis testify (i) to a significant level of genetic diversity in the Northern Eurasian populations and (ii) to a considerable differentiation of gene pool in the population of this region. It has been shown that at the CD4 locus, the frequency of Alu (-) is inversely related to the Mongoloid component of the population, the lowest and highest frequencies of the Alu deletion at locus CD4 were recorded respectively in Eskimo (0.012) and Russian and Ukrainian (0.35). The analysis of gene flow proved Caucasoid populations (Russian, Tajik and Uzbek), as well as those of Turkic ethnic groups from the Southern Siberia (Altaians and Tuvinians) and Khanty and Mansy populations to be the recipients of a considerable gene flow from the outside of the concerned population system, as compared with the East Siberian and the Far East ethnic groups. The results of the correlation analysis received with use polymorphic Alu insertion testify to the greatest correlation of genetic distances with anthropological characteristics of populations.

The review summarizes data obtained by the authors and other laboratories concerning the role of urokinase plasminogen activator in vessel remodeling and angiogenesis. The data have shown that urokinase is involved in unfavorable vascular remodeling during the development of restenosis, atherosclerosis and also in the regulation of angiogenesis. Urokinase is a promising target for therapeutic interventions aimed at restenosis prevention. Urokinase gene therapy may be a perspective strategy for the treatment of tissue ischemia.

The urokinase type plasminogen activator (urokinase) plays a pivotal role in the regulation of cell adhesion and migration during tissue remodeling. Urokinase not only specifically cleaves plasminogen and converts it into plasmin but also activates intracellular signaling upon binding to certain receptors on the cell surface. The polyfunctional properties of this protein are associated with its three-domain structure as follows: the C-terminal proteolytic domain containing the serine protease active center, the central kringle domain, and the N-terminal domain homologous to epidermal growth factor. This review considers functional properties of urokinase and of its fragments generated on the cell surface as a result of proteolytic processing. This review will discuss the mechanisms of urokinase-mediated regulation of cellular function upon binding to membrane receptors.

Urokinase activates adhesion of monocytic U937 cells to fibrinogen-coated surface. This effect is due to urokinase proteolytic activity and does not depend on the urokinase binding to its receptor.

Urokinase is the main component of the fibrinolytic system and comprises two functions. Namely, the catalytic domain enables to trigger the proteolytic cascade in blood and in the vessel wall, stimulating the activation of growth factors, matrix remodelling and smooth muscle cell proliferation. On the other hand, the amino terminal domain of urokinase that is homologous to epidermal growth factor promotes urokinase to bind to the specific receptor. The cell surface binding of uPA may initiate the activation of the second messengers, protein phosphorylation and cell migration. This dual function of urokinase affects vascular growth, as well as the intimal thickening of the vessel wall after intravascular injury. Also uPA and its receptor are implicated in many physiological and pathological processes, including ovulation, embryogenesis, cancer metastasis, inflammation, and wound healing.

The method is based on reconstructing the image of the transverse section of the body on a television screen by means of a computer, depending on the capacity of the tissue to absorb X-rays. A cross-section is constructed on the basis of a large number of projections, where each tissue has its own color in a black-and-white or colour scale. The section obtained is topographo-anatomical and allows the shape, dimension, structure and mutual position of the internal organs to be clearly determined. Twenty one patients suspected of having various lesions of the adrenals were examined. Computer tomography revealed aldosteroma in 3, hyperplasia in 2, pheochromocytoma in 2, connective-tissue fibrosis in 1, carcinoma of the adrenal cortex in 1. No changes were found in 12 patients. Computer tomography makes it possible to clearly determine the size, shape and localization of the glands, but it cannot establish the nosological diagnosis, recording only the presence of a new growth.

Retrospective clinical and mathematical analysis of 168 parameters was performed in 188 patients with arterial hypertension, using standard programmed case history format designed specifically for the purpose. A number of differential criteria were identified and their diagnostic informative value was assessed for each form of arterial hypertension. The isolated criteria were grouped into anamnestic, clinical-laboratory, radioroentgenographic and roentgenoangiographic ones. Anamnestic and clinical-laboratory groups of diagnostic criteria were shown to be acceptable for health services. Their use in prehospital screening of patients is expected to contribute to the diagnosis of basic disease provoking arterial hypertension.