[Interaction of epinephrine and ADP in regulation of platelet function in chronic cerebral ischemia ].

The purpose is devoted to test of hypothesis that patients with chronic cerebral ischemia (CCI) have decreased secretion of platelet ADP as the reason of platelet aggregation restriction in response to stimulation of adrenaline. Methods. We used platelet-rich plasma which was separated by centrifugation from peripheral blood of 55 patients with a diagnosis of CCI of stage 1-2. Platelets aggregation was studied on aggregometer Chrono - Log (USA). ADP and Epinephrine were used for platelet stimulation at effective concentration (EC50). Modulatory role of ADP subthreshold doses (0.5 mM) in platelet activation was analyzed with its addition to a suspension of platelets stimulated by agonists (EC50). Results. In 35 patients (group 1) with platelet hyperreactivity to ADP (EC50) response of platelets to Epinephrine was heterogeneous: in 17 cases (48.6%) there was high response (50%) and in 18 cases (51.4%) there was low platelet response to Epinephrine. 20 patients (group 2) had hyporesponsiveness of platelets upon stimulation by both agonists. It was established that the low initial response of platelets to Epinephrinе in vitro might be due to reduced secretion of ADP, i.e. limited adaptive response since administration of ADP subthreshold doses enhances adrenoreactivity of platelets. If pathochemical violations underlying the formation of platelet disadaptation are reversible, it is possible to recover the reaction of platelets to Epinephrine. Conclusion. In reducing the functional response of platelets to Epinephrinе key issue is establishing the reversibility of violations of platelets adaptive response of platelets.

[Molecular mechanisms of individual platelet reactivity in hematuria secondary to lithotripsy].

AIM: To investigate the mechanisms of individual platelet reactivity to ADP and adrenaline associated with the variability of hematuria after lithotripsy in patients with chronic obstructive pyelonephritis (COPN). MATERIALS AND METHODS: The study included 41 COPN patients admitted to the Department of Urology for lithotripsy (LT). The contact ultrasonic LT was performed using the Karl Storz Calcuson Ultrasonic Lithotripsy System. Postoperative hematuria was assessed by microscopic red blood cell count. Platelets were separated from the citrated peripheral blood by centrifugation. Platelet aggregation was measured by Chrono-log aggregometer using agonists (ADP, adrenaline) at a concentration of EC50 and EU10. RESULTS: There were three types of platelet functional response to ADP and adrenaline after LT (increased, unchanged and decreased aggregation), but the predominant type of individual response was increased platelet aggregation. Testing 24 hours after LT revealed 7 platelet phenotypes differing in functional activity of 2-adrenoceptor agonist and purine receptors (R2Y1 and R2Y12). Normal purine receptor activity was associated with the ability of platelets to respond to adrenaline by increasing the functional activity aimed at limiting hematuria. Reduced platelet response to ADP after LT reaching the level of hyporesponsiveness may be viewed as a predictor of severe hematuria after surgery. CONCLUSION: Individual platelet reactivity, manifested by the interaction of ADP and adrenaline agonist, determines the effectiveness of the increase in pro-aggregation capacity of platelets in developing postoperative hematuria.

[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.

[Interaction of the Humoral Agonist During the Platelets Activation in Patients with Chronic Cerebral Ischemia].

OBJECTIVE: The aim of the study was to determine the effect of the standard drug therapy of 95 patients with chronic cerebral ischemia (CCI) on the functional status of platelets as possible participants of microcirculation of the brain. METHODS: Platelets were isolated from peripheral blood by centrifugation and examined at 24 hours after initiation of standard medical therapy including aspirin (100 mg). The cells were stimulated in vitro using adenosine diphosphate (ADP), epinephrine, platelet activating factor (PAF) and serotonin in an effective concentration (EC50) inducing in healthy individuals platelet aggregation in the range of 50 ± 5%. A study of platelet aggregation was carried out on aggregometer Chrono-Log (USA). RESULTS: Research included 95 patients with CCI 1-2 Stage--82 patients taking antiplatelet and antihypertensive drugs before hospitalization (main group), 13--did not receive these drugs during 7 days prior to hospitalization (comparison group). After start conservative treatment, only ADP induced platelet aggregation, which was similar (p > 0.05) with values in healthy individuals. The pharmacological inhibition of the functional activity of platelets other investigated agonists reproduced hyporesponsiveness of platelets. Against this background, in 34 (41.5%) patients at 24 hours after initiation of therapy occurred potentiation effects of PAF and epinephrine in the test in vitro; whereas the summation of the effects of serotonin and epinephrine on platelets was detected in 12 (14.6%) patients. The basis of this phenomenon may be strengthening effect of ADP secreted from dense-granules, additional stimulation by Gi-protein signaling system by epinephrine and Gq-protein by the action of PAF and serotonin. CONCLUSION: Response to the combined action of platelet agonists may be predictor of the risk of thrombogenesis at CCI.

[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.

[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.

[Age-related features of peripheral blood cell adaptive reaction in women with chronic obstructive pyelonephritis].

The aim of the study was to evaluate the adaptive changes of peripheral blood cells of recurrence inflammation in aged women with chronic obstructive pyelonephritis (COPN). An analysis of clinical and laboratory data was carried out on 50 women who were distributed into two age periods: under 55 years (the comparison group) and over 65 years. In women of 65+, during recurrence of COPN, the degree of leukocyte increase, neutrophils, monocytes and erythrocyte sedimentation rate (ESR) reached 90,1, 20,8, 71,4 and 31,6%, whereas lymphocyte count was less by 2,8 times in comparison with remission. In women under 55 years (in recurrence of COPN), degree of leukocyte increase was 87% (p<0,001), neutrophils--4, 8% (p<0,05), monocytes--in 2,04 times (p<0,001), ESR was less in 3,1 times (p<0,001) and lymphocyte count was less than 19,5% (p>0,05). The manifestation of neutrophilocytosis and lymphocytopenia might be due to age-related features of adaptive reaction in peripheral blood cells during the COPN recurrence.