[Effect of acetylsalicylic acid in complex with lipid nanostructures of various compositions on human platelet aggregation].

The effect of lipid nanocomplexes loaded with acetylsalicylic acid (aspirin) on platelet aggregation in vitro was investigated. The antithrombotic effect of aspirin in complex with liposomes prepared from pig brain glycosphingolipids is not only significantly higher compared to control, but also accompanied by leveling of the development of proaggregant effects. It was shown that ADP-induced platelet aggregation is reduced by the introduction of electrostatic charge in the structure of lipid bilayer of liposomes. The effect achieved for the liposomes possessing a negative charge was more pronounced in comparison to the effect of positively charged liposomes.

[Changes of haemostatic parameters in patients with acute cardioembolic stroke].

Haemostatic parameters: platelet aggregation, hematocrit, fibrinogen, antithrombin III, fibrinolytic activity and euglobulin lysis time, plasminogen, plasminogen activator and anti-activator activity, thrombin- antithrombin and plasmin-antiplasmin complexes and serum von Willebrand factor were studied at the most acute stage of cardioembolic stroke (1-7 days after development of neurological symptoms). State of the vascular wall was assessed using the "cuff"-test. The activation of hemostasis in patients with cardioembolic stroke was characterized by the hypercoagulation and decrease of fibrinolysis and athrombogenic potential of vessel wall properties (antiaggregation, fibrinolytic and anticoagulative). In conclusion, haemostatic disbalance and decreasing of athrombotic potential of the vessel wall may be the indicator of embolism in patients with cardioembolic stroke.

Platelet aggregation and endothelial function in patients with complicated essential hypertension (ischemic stroke) and coronary heart disease.

In patients with complicated essential hypertension (ischemic stroke) and coronary heart disease, inductors of platelet aggregation in various doses induced "paradoxical" changes in platelet aggregation activity reflecting the degree of decompensation under conditions of persistent endothelial dysfunction. Aggregation inductors in low doses were shown to have a greater diagnostic significance. The content of endothelial dysfunction markers in the blood was persistently elevated under these conditions.

[Chronic cerebrovascular diseases, metabolic syndrome and the status of hemorrheological and hemostatic systems].

AIM: to study an association between metabolic syndrome and endothelial dysfunction as a regulator of hemorrheological and hemostatic processes in patients with chronic forms of cerebral circulatory insufficiency. SUBJECTS AND METHODS: Forty-six patients with chronic cerebrovascular diseases (CCVD) were examined; of them 23 patients were diagnosed as having metabolic syndrome (MS). Clinical manifestations and major hemorrheological and hemostatic parameters, such as platelet and erythrocyte aggregation, fibrinogen, hematocrit, von Willebrand factor, antithrombin III, intercellular adhesion molecules (IAM), etc., were estimated. Endothelial dysfunction was studied from the data of cuff test (CT). RESULTS: MS promotes a higher degree of clinical symptomatology in patients with CCVD and more significant impairments in the hemorrheological and hemostatic systems. CT has shown that all the patients have an inadequate endothelial reaction - the antiaggregatory, fibrinolytic, and anticoagulant activities of the endothelium are lowered. There was endothelium-dependent hyperproduction of IAM. CONCLUSION: The found changes suggest that MS has a considerable impact on the formation of a significant procoagulant state of the hemorrheological and hemostatic systems in patients with CCVD.

[Hemorheology and hemostasis in patients suffering from ischemic cerebral stroke and metabolic syndrome].

A high level of mortality and disability makes study of various aspects of ischemic cerebral stroke (ICS) an extremely important problem. Presently, combination of various cardiovascular risk factors significantly increases the probability of such life-threatening conditions as ICS. Such risk factors as arterial hypertension, dyslipoproteinemia, excessive body weight, glucose intolerance or diabetes are often combined, which led to a suggestion to consider them together as one symptom complex, metabolic syndrome (MS). It is evident that MS affects the functioning of different organs and systems, including the systems of hemorheology and hemostasis. These are changes in hemorheological and hemostatic parameters that play a leading (in some cases decisive) role in the development of ICS. The present study found that the presence of MS in ICS patients hindered improvement in hemorheological and hemostatic parameters in the course of the disease. This was manifested by the absence of positive changes in thrombocyte aggregation, as well as fibrinogen level elevation in patients with MS in the course of treatment. Elevated blood level of D-dimers within the whole acute period in most MS patients also reflected more active thrombus formation. The development of ICS is very unfavorable to the condition of vascular wall athrombogenic activity in all patients. At the same time, worsening in all the chains of endothelial wall athrombogenic ability was more prominent in MS patients. Significant influence of MS on the forming of prothrombotic condition, which determines unfavorable clinical course of ICS, was demonstrated.

[Hemorheology and homeostasis in the most acute stage of lacunar stroke].

Eighty patients were studied at the first day of the development of lacunar stroke, the main attention being focused on the particular form of focal pathology--a small deep (lacunar) stroke (SDS). Patients with arterial hypertension and complication free course had higher hemorheologic parameters (blood viscosity, erythrocytes aggregation) and a shift of prostacyclin-thromboxane balance towards preaggregation and decrease of fibrinolysis. These disturbances strengthened during the development of SDS. The endothelium dysfunction, alterations of blood rheologic characteristics due to the formation of aggregants of erythrocytes, decrease of erythrocytes deformation and activation of cell homeostasis play a central role in the development of intracranial arterial occlusion resulted in the SDS development. At the same time, fibrinolysis remains relatively stable.

[Ischemic stroke: hemostasis and factors of cerebral embolism].

Hemorheology and hemostasis in patients with ischemic stroke in comparison to the process of cerebral embolism are considered. Results of transcranial Doppler monitoring of microembolic signals and indices of coagulation and anticoagulation blood systems are analyzed. The changes of both hemorheology and hemostasis in ischemic disturbances of blood circulation are characterized by an increase of coagulation blood activity and suppression of anti-coagulation activity. In ischemic stroke, as compared to transitory ischemic attacks, the markers of thrombinemia were increased significantly that was most pronounced in cases of lacunar and cardioembolic genesis. Cerebral microembolism was associated with imbalance of hemostasis systems. The results of the study may be used in elaboration of recommendations for optimization of therapeutic arrangements in ischemic disturbances of cerebral blood circulation.

[A state of hemorheological system in patients subjected to carotid endarterectomy with atherosclerotic lesion of the major cerebral arteries].

To study the influence of changes in the blood rheological indices and blood coagulation on development, progression and clinical course of restenosis and thrombosis, 62 patients (mean age 63.4 +/- 6.0 years), were followed up for 2-15 years after carotid endarterectomy. Above 50% (maximum 70%) restenosis was observed in 7% cases. No critical postoperative restinosis was observed. In 12% patients, restenosis was accompanied with carotid artery occlusion and hematocrit, with fibrinogen (FG) being significantly increased in the absence of fibrinolytic activity (FL) elevation, indicating hemorheological disorders and homeostasis activation in such patients. Long-term follow-up showed that viscosity blood characteristics were elevated but functional activity of platelets and FA in patients did not differ from those in healthy subjects. At the same time, FG was high and fibrinolysis index was lower than mean statistical value that indicated predominance of blood procoagulation activity.

[The wavelet analysis at heliobiological connections]. / Veivlet-analiz v geliobiotropnykh sviaziakh.

The Wavelet analysis of the time series of the number of insults per day and the variations of heliogeophysical indices was carried out. The patterns of Wavelet coefficients for both processes show a complex nonstationary behavior and the presence of periodic and acyclic constituents on different scales. During heliogeophysipal disturbances, the energy contribution to the processes increases more than threefold compared with the mean value on scales from three to five days.

[Effects of helio-geomagnetic disturbances on the human hemorheological characteristics]. / Vliianie geliogeomagnitnykh vozmushchenii na gemoreologicheskie kharakteristiki liudei.

Effects of geomagnetic disturbances on the rheological characteristics of blood and the homeostasis system were studies in 62 essentially healthy men. Rheological blood parameters, i.e. viscidity, hematocrit, fibrinogen, and erythrocyte and thrombocyte aggregation demonstrated statistically significant responses to alterations in the solar and geomagnetic activities. The authors raise a discussion about mechanisms of the physical processes in the near-Earth space on the blood rheological parameters.

[The follow up of patients with extracranial pathology of the carotid arteries and ischemic disorders of cerebral circulation]. / Katamnez bol'nykh s ékstranial'noi patologiei sonnykh arterii i ishmicheskimi narushaniiami mozgovogo krovoobrashcheniia.

According to the populational studies, about 50% of ischemic disorders of cerebral circulation, both persistent and transient, are induced by thrombotic or embolic complications of atherosclerotic plaques which produce an adverse effect on the large and small caliber arteries; about 20-25% is associated with lesion of the small diameter intracranial vessels, about 20% with embolism from the heart, and the remaining disorders fall within other rare causes. The prevalence of atherosclerotic lesions of the vessels feeding the brain, the severity of their clinical manifestations, insufficient efficacy of conservative therapy and the high risk of surgical treatment remain as before a matter of great medical and social concern. In connection with an appreciable progress of vascular surgery carotid endarterectoray (GEAE) as one of the radical approaches to correction of the pathology of the carotid artery segment is widespread at the large centers of vascular surgery of different countries. However, in spite of the fact that CEAE is an advanced and radical technique of preventive operation, it produces only a local effect on vascular diseases whereas the other, no less important pathogenetic mechanisms leading to disorders of cerebral circulation remain unchanged and demand drug correction to avoid repeated disorders of cerebral circulation. Analysis of the long-tern results evidences a stable and lasting effect of CEAE. The postoperative clinical manifestations can be used as the main criterion for the efficacy of CEAE, especially as compared to the purely conservative therepy. The results of the long-term follow up (over the period as long as 15 years) of a large group of operated patients demonstrate that the majority of them did not show the emergence of the new focal neurologic symptomatology in the ipsilateral hemisphere and only a small percentage of cases developed stroke. The major western statistics provide the analogous results.

[Response of the human body to heliogeophysical disturbanes]. / Reaktsiia organizma cheloveka na geliogeofizicheskie vozmushcheniia.

A correlation between variations in the medical parameters and the heliogeophysical indices describing physical processes during solar storms was established. It was proposed that one of the reasons for the biotropic effects observed is rheological shifts of human blood during enhancement of solar activity. The influence of heliogeophysical disturbances on the rheological properties of blood was investigated.

[Cardiogenic ischemic strokes: pathogenetic aspects]. / Patogeneticheskie aspekty kardiogennykh ishemicheskikh insul'tov.

Eighty-three patients with acute ischemic stroke (56 men and 27 women, mean age 90.1 +/- 10.8 years) were examined in order to elucidate the significance of paroxysmal heart rhythm disorders and silent myocardial ischemia and determine the pattern of hemorheological changes. Traditional clinical instrumental examinations were supplemented by Holter monitoring and measurements of a wide spectrum of hemostatic and hemorheological values. Cardiogenic ischemic strokes were pathogenetically heterogeneous. Holter monitoring helped detect the significance of paroxysmal atrial fibrillation in the pathogenesis of embolic cardiogenic stroke. One of the key factors in development of hemodynamic cardiogenic stroke was transitory bradyarrhythmia and deterioration of left-ventricular contractility. Cardiogenic strokes are associated with hemostatic activation with predominant changes in the plasma hemostasis, which dictates purposeful hemocorrection.

[Use of allikor for the normalization of fibrinolysis and hemostasis in patients with chronic cerebrovascular diseases]. / Ispol'zovanie allikora dlia normalizatsii sistem fibrinoliza i gemostaza u bol'nykh s khronicheskoi tserebrovaskuliarnoi patologiei.

A new form of garlic preparation--long-acting tablets of garlic powder allicor has been studied in patients with cerebral atherosclerosis (CA) complicated by chronic cerebrovascular pathology. A double blind placebo-controlled trial examined allicor effects on hemostasis and fibrinolysis in cross-over groups at two stages. At the first stage patients of group 1 (n = 15) received allicor in a dose 600 mg/day; patients of group 2 (n = 14) were given placebo. At the second stage group 1 received place and group 2 allicor in the same regimen. Before the treatment allicor effects on platelet aggregation and fibrinolysis were studied in vitro (20 patients). Allicor significantly inhibited ADP-induced platelet aggregation in vitro and ex vivo, reduced blood fibrinogen, normalized initially low fibrinolytic activity and fibrinolysis index. Due to the above properties allicor can be used for prevention and treatment of CA complicated by chronic cerebrovascular pathology.

[The changes of lipids, lipoproteins and apolipoproteins in plasma in ischemic stroke]. / Izmenenie soderzhaniia lipidov, lipoproteinov i apolipoproteinov v plazme krovi pri ishemicheskom insul'te.

Contents of lipids (cholesterol CS, triglycerides) as well as levels of CS of lipoproteins of different density and of apolipoproteins A1 and B were measured in blood serum of 31 patients in different periods after of ischemic stroke. The majority of the indices studied were significantly decreased in men in acute periods of the stroke, especially in 8-21 days after the stroke development. Meanwhile, the levels of lipids, CS lipoproteins of both low and very low densities were increased later. Contents of CS of antiatherogenic lipoproteins of high density (HDLP) was low in different periods after the development of disorders of cerebral circulation. This confirms the concept that low level of HDLP is one of the risk factors of ischemic stroke. Decrease of the levels of both lipids and CS of lipoproteins of different density was more pronounced in patients with more severe atherosclerotic damages of the main cerebral arteries. Disorders of metabolism of lipoproteins in ischemic disorders of cerebral circulation are discussed with reference to literary data taking into consideration their heterogeneity. Genetically determined pathology of certain apolipoproteins plays a key role factor in the development of early atherosclerosis and in the elucidation of biochemical markers of the primary damages of cerebral vessels.

[Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant]. / Aksolong: novaia bukkal'naia forma atsetilsalitsilovoi kisloty dlia primeneniia v kachestve antiagreganta.

AIM: Study of the tolerance and pharmacodynamic and pharmacokinetic characteristics of ascolong, a new buccal dosage form of aspirin containing a very low dose of acetylsalicylic acid (ASA): 12.5 mg. MATERIALS AND METHODS: The study was carried out in 43 healthy men (assessment of the drug tolerance) and 19 male patients with coronary disease or cerebrovascular disorders. In 10 patients the antiaggregant efficacy of ascolong administered once or regularly (for 2 weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of each course before and 2, 4, and 24 h after the drug intake. RESULTS: Ascolong containing a very low dose of ASA exerts a reliable antiaggregant effect after a single and regular intake, although this effect is less manifest than after aspirin tablets. Profiles of ASA concentrations in the blood were studied. Transbuccal entry of ASA in systemic circulation decelerated its metabolism into a less active metabolite, salicylic acid, due to which fact the ASA microdose had an expressed antiaggregant effect. The drug was sufficiently well tolerated. CONCLUSION: The new buccal film form of aspirin containing a very low dose of ASA possesses a good antiaggregant effect and is promising in subjects with contraindications to oral intake of aspirin.

[Effect of carnosine and its derivatives on ADP-induced human platelet aggregation]. / Vliianie karnozina i ego proizvodnykh na ADF-indutsiruemuiu agregatsiiu trombotsitov cheloveka.

ADP-induced aggregation of thrombocytes was studied in patients with cerebrovascular impairments as well as after treatment with carnosine and its native derivatives; these drugs proved to be modulators of the cell aggregation. Carnosine decreased the rate of thrombocyte aggregation in patients with high index of aggregation and exhibited the proaggregation activity in patients with low rate of aggregation. The antiaggregation activity of the preparations studied, used at physiological concentrations 3.5 mM, was increased as follows: carnosine (17%) < histidine < acetyl anserine < ophidine < anserine (35%). Application of carnosine and its native derivatives may be promising and effective in correction of thrombocyte functional properties in patients with cerebrovascular impairments.

[Clinical and blood rheologic effects of ticlid in patients with cerebrovascular diseases]. / Klinicheskie i gemoreologicheskie éffekty tiklida u bol'nykh tserebrovaskuliarnymi zabolevaniiami.

Clinical efficacy of tiklid in a dose 500 mg/day and its action on platelet vascular hemostasis were evaluated in 24 patients with cerebrovascular diseases. A 15-day tiklid course promoted a regress in some subjective symptoms (headache, vertigo, walking instability, photopsias, etc.), the objective neurological status being unchanged. Tiklid had a positive influence on some rheological parameters and platelet vascular hemostasis. ADP-induced platelet aggregation, blood fibrinogen levels got reduced. The platelets sensitivity to antiaggregation agent PgI2 in vitro arose. Antiaggregation potential of the vascular wall returned to normal in 33% of patients with initially low or inverse response.

[Status of microcirculation and rheological properties of blood in patients with cerebral circulatory disorders]. / Sostoianie mikrotsirkuliatsii i reologicheskikh svoistv krovi u bol'nykh s distsirkuliatornoi éntsefalopatiei.

Microcirculation and rheological properties of blood were investigated over time on the basis of the findings of biomicroscopy of the bulbar conjunctiva in 61 patients with different stages of circulatory encephalopathy in the presence of arterial hypertension and atherosclerosis. Rheological properties of blood were changed at all stages of disease. Correlations between the ability of erythrocytes to aggregation and the degree of their intravascular aggregation by the findings of biomicroscopy of the bulbar conjunctiva were not found. The importance of investigation of the intravascular aggregation of erythrocytes and theological properties of blood for assessment of the cerebral vascular microcirculation, control of therapy, and verification of some aspects of the mechanism of action of various drugs was shown.