[The recovery of the function of hyporesponsive platelets during the antiplatelet therapy in patients with chronic cerebral ischemia]. / Vosstanovlenie funktsional'noĭ aktivnosti giporeaktivnykh trombotsitov pri antiagregantnoĭ terapii u patsientov s khronicheskoĭ ishemieĭ golovnogo mozga.

AIM: To establish the ability of recovery of platelet proagregation status in patients with chronic cerebral ischemia receiving standard medical therapy. MATERIAL AND METHODS: Thirty patients were studied. Platelets were isolated from peripheral blood by centrifugation. For in vitro platelet stimulation we used ADP, epinephrine and PAF. Platelet aggregation was recorded on aggregometer. RESULTS AND CONCLUSION: 24 hours after the beginning of standard therapy, the patients had 13 platelet phenotypes related to the functional state of three main receptors (purine receptors P2Y1 and P2Y12, α2-adrenergic receptors, and PAF- receptors. After 9-21 days of treatment (before discharge from the hospital), 15 patients (50%) had platelet phenotypes that did not change, i.e. standard medical therapy did not affect the performance of at least one of the receptor clusters, so the risk for initiation of thrombogenesis still remained. Remaining 15 patients had a phenotype with low platelet reactivity to all three agonists studied - cluster [ADP (↓) epinephrine (↓) PAF (↓)] indicating the achievement of antiplatelet effect. The given phenotype is characterized by summation or potentiation of the effects of agonists - ADP and epinephrine in 6 cases (40%), epinephrine and PAF in 6 (40%), ADP and PAF in 3 (20%), which means that conditions for recovery of functional activity of hyporeactive platelets could be further created.

[The age characteristics of reaction of leukocytes in males under chronic obstructive pyelonephritis].

The leucocytosis and increase of numbers of neutrophils are two indicators commonly applied to evaluate acute inflammatory reaction. At that, the normality reference range is a standard of comparison. Considerably more often occurs the need to evaluate severity of patient condition or expression of inflammation determined by individual reactivity of organism. In this context the reaction of leukocytes was analyzed in 80 males of three age categories: younger than 55 years, 55-65 years and older than 65 years. All participants of study had verified diagnosis of chronic obstructive pyelonephritis. The comparison of leukopoiesis and erythrocyte sedimentation rate at the phase of remission and recurrence of chronic obstructive pyelonephritis of each age category made it possible to single out groups of patients with different reactivity of organism. In perspective, a possibility appears to individualize tactics of conservation therapy under chronic obstructive pyelonephritis and to evaluate its effectiveness.

[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.

[Functional activity of monocytes and mechanisms of iNOS intracellular regulation during wound process].

To investigate the dynamics and mechanisms of iNOS activity during wound process, the peripheral blood monocytes of 22 patients with acute foot wounds were analyzed. The basal and LPS-stimulated nitrites production was estimated at 1, 3-4, 7-10 and 14-18 days of wound process. iNOS activity and its molecular regulation was estimated by the inhibitory analysis. It was shown that since 1 to 3-4 day of wound process the basal and LPS-stimulated activity of iNOS, PDE and 5-LOX were elevated initially and than decreased. The COX and PkC activities increased after 3 days and reached the maximum level at days 7-10. The activity of PkA, which inhibits iNOS, intensively increased form 7-10th to 14-18th days of healing, and was accompanied by arginase-1 stimulation. Thus monitoring of intracellular signaling system can be used for diagnostics and correction of wound healing.

[Modulation of platelet tyrosine phosphatases by arachidonic acid metabolites in diabetes mellitus complicated with acute pyogenic inflammation].

To estimate the ability of intracellular tyrosine phosphatases modulation by arachidonic acid metabolites in patients with diabetes mellitus 2 type during foot wounds healing the inhibitory analysis of platelets aggregation induced by ATP plus inhibitors of tyrosine phosphatases, cyclooxygenases and 5-lipoxygenases was performed in 16 patients during hospitalization, at 3-5, 10-14 and 30 days of therapy. It was shown that foot wound healing in diabetic patients was associated with optimization of proteins tyrosine phosphorylation and cells arachidonic acid metabolism. It means the diagnostic significance of tyrosine phosphorylation and eicosanoids to interpret the result of wound healing at diabetes mellitus.

[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

[Molecular mechanisms of the iNOS regulation disorders in monocytes of patients with diabetic foot syndrome].

The activity of inducible synthase of nitrogen oxide (iNOS) and its modulators in vitro, while stimulation by lipopolysaccharides (LPS), was investigated in 36 patients with diabetic foot syndrome for the objective of complex estimation of monocytic functional state and its role in regulation of the cutaneous wound healing. The monocytic iNOS basal activity raising with simultaneous restriction of answering on LPS was noted. It was accompanied by enhancing of AT1-receptors sensitivity, as well as activity of proteinkinase C (PkC), phosphodiesterase (PHDE) and 5-lipoxigenase (5-LOG) on a background of cyclooxygenase (COG) activity lowering and significant inhibiting of proteinkinase A (PkA). Positive dynamics of the wound process was observed in 10 - 14 days, coexistent with the iNOS basal activity restriction. In the structure of answering on LPS there were noted significant reduction of 5-LOG/COG and PkC/PkA ratio, as well as PHDE activity and the AT1-receptors sensitivity lowering. But, even in case of the wound surface epithelization completion some disorders were saved in 24 - 30 days, causing support of the monocytes iNOS tolerance to LPS.

[Adrenergic reactivity and course of the wound process in diabetes mellitus condition: diagnostic significance and pathogenetic interpretation].

In order to establish interrelationship between the organism adrenoreactivity and the wound process course in presence of diabetes mellitus the dynamics of effective concentration of alpha2-adrenoreceptors agonist (alpha2-AR), causing aggregation of 50% of thrombocytes (EC50) in patients, suffering diabetes mellitus, complicated by purulent-necrotic affection of lower extremities in admission to the hospital and during the period of treatment, was studied. The cutaneous wounds healing was accompanied by the organism adrenoreactivity normalization, in condition of durable unhealing of the wound the alpha2-AR sensitivity tolerance to the therapy performed was noted. It permits to consider the EC50 index as a criterion of severity of dysregulation changes and the therapy efficacy.

[Modulating effects of protein kinase A on intracellular signal systems in the course of skin wound healing in patients with diabetes mellitus].

The purpose of this study was to examine the modulating effects of protein kinase A (PKA) on the performance of signal systems triggered while activating alpha2-adrenoceptors and eNOS in the course of a wound process in patients with type 2 diabetes mellitus. Patients with the diabetic foot were shown to have impaired adrenergic responsiveness, accompanied by reduced eNOS activity and PKA inhibition. The positive therapeutic effect was noted with the increased stimulating effect of the PKA system on PKG on days 3 to 5 and on eNOS on days 10-14 of therapy. The preserving eNOS activity deficit was compensated for by the PKA-induced increase in PKG stimulation. The modulating effects of PKA are a compensatory intracellular mechanism of adaptation when NO production is decreased, which may be used to develop new therapeutic corrections of the dysregeneratory syndrome.

[State of intracellular signaling systems in endothelial dysfunction].

To estimate the state of different parts of intracellular signaling system associated with NO production after a2-adrenoreceptors stimulation under endothelial dysfunction in 22 patients with diabetic foot, the inhibitory analysis of clophelin-induced platelets aggregation modulation by administration of eNOS stimulator (L-arginin) and inhibitor (L-NAME), modulator of Ca-calmoduline (triphtazine), guanilate cyclase stimulator (sodium nitroprusside), inhibitors of phosphodiesterases (theophillinum) and protein kinase A (butamide). It was shown that endothelial dysfunction in patients with diabetic foot is associated with alteration of adrenoreactivity and inhibition of eNOS, guanilate cyclase, protein kinase A and stimulation of phosphodiesterases activity.

[Biogenic amines in rat brain structures in an adjuvant arthritis model]. / Biogennye aminy v strukturakh mozga krys pri modelirovanii ad"iuvantnogo artrita.

The role of changes in biogenic amines neurochemistry in cerebral structures in abnormal immunoreactivity accompanying development of autoimmune disease was investigated in experiments on 24 Wistar male rats. Biogenic amines and their metabolites (dopamine, dioxyphenylacetic acid, serotonin, oxyindolacetic acid) were assays in the sensomotor cortex, hypothalamus and hippocamp by means of high-performance liquid chromatography. Development of adjuvant arthritis was associated with definite neurochemical changes in the brain: inhibition of serotonin metabolism and enhancement of dopaminergic systems in the hypothalamus and sensomotor cortex. Prophylactic administration of oil solution D,L-alpha-tocopherol acetate promoted enhancement of serotonin metabolism in hypothalamic and hippocampal neurons. Bitemporal exposure to UHF electric field aroused stronger effects on the neurochemical metabolism in hypothalamic, hippocampal and sensomotor cortex neurons than TPA. It is concluded that bitemporal exposure to UHF electric field and antioxidant activate central immunoreactivity mechanisms in animals with adjuvant arthritis. Serotonin and dopamine systems in this process are leading.