[Purine receptors and associated signaling systems in regulation of platelet function].

Purine receptors of platelets play key role in hemostasis and thrombogenesis and they are used as targets for antiplatelet therapy. Platelets express three subtypes of purine receptors--P2X1, P2Y1 and P2Y12. The expression, ligands and sensitivity of purine receptors of platelets and their role in thrombogenesis are discussed in this article. Authors debate information about basic molecular mechanisms, links with intracellular signaling and biological effects of purine receptors activation. In conclusion, understanding of signaling mechanisms of purine receptors is a basis for further pharmacological strategy and effective antiplatelet therapy development.

[The impact of antisecretory therapy on gastroduodenal ulcers healing after acute bleeding].

In this paper we compared the efficacy of proton pump inhibitors (PPIs) and H2 receptor antagonists on the morphogenesis of the marginal zone of gastric and duodenal ulcers in 56 patients withacute gastroduodenal bleeding. It is shown that the antisecretory drugs in the treatment of patients with acute ulcerative bleedingnot only affect on the secretory activity of the glands in gastroduodenal zone, but it also modulates inflammatory reparative process and the status of mucous and bicarbonate barrier. A greater anti-inflammatory effect of PPI in comparison with H2-receptor antagonists has been proved. Appointment of PPIs had more pronounced stimulation of angiogenesis and cell proliferation of the surface epithelium.

[Molecular mechanisms of thrombogenesis].

Platelets are the key elements of hemostasis and optimal model for analysis of normal and altered mechanisms of thrombogenesis. Adhesion of platelets is initiated by von Willebrand factor, collagen, fibronectin, thrombospondin and laminin through GP VI, GPIb-V-IX complex, integrine receptors α(2)ß(1), α(IIb)ß, and Fc(γ)-receptors IIA. Their activation is accompanied with signalosome formation, increase of intracellular Ca2+ level, proteins phosphorylation, adhesion and degranulation of platelets. Major stimulators of progression phase are humoral factors and factors accumulated in dense granules of platelets, which include ADP, TA2, epinephrine, serotonin and thrombin. Their action is mediated by stimulation of G-protein coupled receptors: Gq, Gi, Gs, Gz, G12, G13, which can modulate activity of adenilate cyclase, phospholipase C, phosphoinositid-3-kinase, p115-RhoGEF and promote recruitment of platelets in the zone of injury. The phase of stabilization is due to contact-dependent signaling by integrins - predominantly α(IIb)ß(3), which ligand is fibrinogen, inducing reorganization of cytoskeleton in platelets, formation of strong intercellular junctions and retraction of thrombus.

[The role of purine receptors of thrombocytes in regulation of hemostasis].

The article discusses the role of ADP and ATP and their receptors in regulation of functional state of thrombocytes, maintenance of vessel wall homeostasis and coordination of inflammatory reparative process. The thrombocytes carry three modes of purine receptors: P2X1 (cationic channel activated by ATP) P2Y1 and P2Y12 (associated with G-proteins and activated by ADP). The article considers intracellular mechanisms of implementation of effects of ADP and ATP in thrombocytes6 mechanisms of their desensitization, relationship with metabolism of arachidonic acid and tyrosine kinase and role in regulation of intracellular concentration of Ca2+. The data concerning polymorphism of receptors P2Y is presented. The role of this phenomenon in thrombogenesis disorders, development of pathology of cardio-vascular system and resistance to anti-thrombocyte therapy is discussed.

[Interdisciplinary integration as an instrument for development a standard of medical education].

The formation of a competent doctor must be based on teaching standards for each discipline, the development of which is possible only as a result of provision of a real interdepartmental integration. The fundamental subjects must be taught not on the assumption of narrow professional interests, but in accordance with the requirements and demands of the clinical disciplines. The fulfillment of this task requires the development of a single computer base "Standards of Medical Education" and elaboration of the interdisciplinary modules. These must be based on the analysis of the "demand" of clinical Departments for new information blocks, the distribution of these blocks into different parts of the syllabus, their filling with the appropriate content, development of the adequate forms and methods of teaching.

[Blood monocytic L-arginine metabolic changes in diabetic foot syndrome].

An inhibition test was used to study mechanisms responsible for L-arginine metabolic disturbances in the blood monocytes of patients with diabetic foot syndrome (DFS). It showed enhanced baseline iNOS activity and inhibition of the arginase pathway with lower nitrite production in response to the administration of lipopolysaccharide in the monocytes of patients with DFS. Impaired L-arginine metabolism was related to the higher activities of protein kinase C (PKC), phosphodiesterase (PDE), and 5-lipoxygenase (5-LO) along with decreased cyclooxygenase activity and drastic protein kinase A (PKA) inhibition. Within the first week, no changes in the wound process were associated with persistent metabolic disturbances of arachidonic acid and serine-threonine kinases with the higher sensitivity of AT1 receptors. In patients with DFS, the condition for wound process termination was decreased baseline iNOS activity and enhanced arginase-1 activity during PKA stimulation with the lower activity of 5-LO, PDE, and PKS. However, impaired mechanisms in the regulation of monocytic L-arginine metabolism persisted even a month later, which predetermines skin remodeling disturbance and the likelihood of recurrent DFS

[Mathematical modeling of kinetics of the tegumental-socket gastric epithelium].

With the aim of formalization of gastric epithelium kinetics estimation the morphometric analysis of gastric mucosa bioptates was performed in 26 patients without endoscopic signs of stomach pathology. During step estimation of gastric pits at different depth authors analyzed changes of cells size, nucleocytoplasmic ratio, coefficient of nucleus elongation in immature cells of pit bottom (11 zone), differentiating cells in pit intermediate zone (L2), and on mucosa surface (L3 zone). Authors used claster and neuronet analysis (by Statistica and MedStat) to make the mathematical model which permit to determine the proportion of functional zones in normal pit (L--33 +/- 3%; L2--27 +/- 3%; L1--40 +/- 3% of gastric pit depth) and to develop the system of cell standards for each zone. These results can be used to diagnostic of gastric epithelium differentiation changes under pathology and to interpret the barrier properties of gastric epithelium.

[Histophysiology of hair follicles: current concept]. / Sovremennye predstavleniia o gistofiziologii volosianykh follikulov.

Hair follicle histophysiology importance isn't limited by hair role in psychosocial consequences. More scientists consider the hair follicle as an attractive system for studying major biological phenomena because the hair follicle is a regenerating system. In this review we revisit the current information about histophysiology and control of hair follicle cycling. All mature follicles undergo a growth cycle consisting of following phases: growth (anagen), regression (catagen) and rest (telogen). We attempt to integrate the morphology with the physiology and molecular biology. Hair follicles are influenced by environmental, systemic and local factors. The most interesting point of this problem is discussed--an integral regulation of hair follicle cycle by systemic, intertissue and intercellular interactions.

[Morphometric characteristics of the kidney nephrogenic zone in newborn rats]. / Morfometricheskaia kharakteristika nefrogennoi zony pochek novorozhdennykh krysiat.

The aim of this work was to give a quantitative characteristic of nephronogenesis and to select the morphometric criteria, which adequately reflect the dynamics of morphogenetic processes. As the study object, the nephrogenic zone of a newborn rat kidney was used, that was examined in sections stained using histological and histochemical methods. The development of nephron structures and of the stroma was followed, and it was established that grading the degree of differentiation of the structures, comparison the nephrogenic zone, reflects the system of current concepts on the inter-inductive influences, which are realized between the distal portions of collecting ducts and nephrogenic cells, epitheliocytes of developing tubules and stromal cells. The morphometric parameters obtained could be used for interpretation of the data on the velocity of nephron formation and tubulogenesis, as well as on the intensity and quality of vascular glomeruli formation.

[Mechanisms of adrenal embryogenesis]. / Mekhanizmy émbriogeneza nadpochechnikov.

The aim of this vie is to discuss the general principles of prenatal development of adrenal gland. On the basis of spatial-temporal heterogenity of structural particularites of fetal adrenal cortex, spectrum steroidogenic enzymes and secreting hormones expression in adrenocorticocytes, regulation of proliferation and differentiation processes mechanisms, authors discuss adrenal morphogenesis in three periods of gestation. It was noted the close relationship between placenta development and hypothalamo-pituitary-adrenocortical system formation with specification in each gestation period. Adrenal embryogenesis accompanied by remodeling of structural, functional and biochemical properties of parenchimal-stromal elements of fetal organ. Definitive zonation formation determined by morphogens: ACTH, renal and intraadrenal angiotensin II, estrogens, prostaglandines and other. The action of these factors realization is due to immediately and thought growth factor system (IGF-I, IGF-II, EGF, bFGF), working as paracrine amplificators of morphogenetic signals and activators of transcriptional factors--c-fos and c-jun.