[In vitro lipid-lowering and fibrinolytic effects of regulatory leucine-containing glyprolines in human blood].

The lipid-lowering, fibrinolytic, and anticoagulant effects of leucine-containing glyprolines, Pro-Gly-Pro-Leu and Leu-Pro-Gly-Pro, were studied in vitro in the blood of patients with disorders of lipid metabolism. The lipid-lowering impact of glyprolines and their ability to reduce the polymerization and to increase the depolymerization of fibrin in human blood were found. Possible mechanisms of lipolytic action of peptides by means of modulation of the lipid-dependent phospholipase A2 were proposed.

[Proignostic Factors of Cardiovascular Complications After Ischemic Stroke].

We included into prospective cohort observational study 148 patients with ischemic stroke aged 60 [52; 68] years. Duration of a prospective follow-up was 35 [28; 40] months. Cardiovascular events (CVE) registered during follow-up were recurrent stroke, transient ischemic attack, myocardial infarction, unstable angina, congestive heart failure, including acute decompensation of chronic heart failure requiring hospitalization, cardiovascular death. During follow-up 37 patients (25%) had 50 CVE. On multivariate regression analysis, independent predictors of CVE after ischemic stroke were: age over 67 years, presence of chronic ischemic heart disease, high grade ventricular arrhythmias, standard deviation of cardiointervals (SDNN) less than 71 ms, absence of thiazide diuretics in the basic antihypertensive therapy.

[Prognostic Factors of Cardiovascular Complications After Ischemic Stroke].

We included into prospective cohort observational study 148 patients with ischemic stroke aged 60 [52; 68] years. Duration of a prospective follow-up was 35 [28; 40] months. Cardiovascular events (CVE) registered during follow-up were recurrent stroke, transient ischemic attack, myocardial infarction, unstable angina, congestive heart failure, including acute decompensation of chronic heart failure requiring hospitalization, cardiovascular death. During follow-up 37 patients (25%) had 50 CVE. On multivariate regression analysis, independent predictors of CVE after ischemic stroke were: age over 67 years, presence of chronic ischemic heart disease, high grade ventricular arrhythmias, standard deviation of cardiointervals (SDNN) less than 71 ms, absence of thiazide diuretics in the basic antihypertensive therapy.

[Circulating in blood plasma cell-free DNA in the pathogenesis of ischemic stroke: the role of the transcribed region of ribosomal repeat].

It has been established that DNA, in addition to its basic functions (storage and realization of genetic information), also carries CpG-rich sequences having immunopotentiating properties. In this study we investigated the dynamics of the quantitative and qualitative characteristics of cell-free DNA (cfDNA) circulating in blood plasma of patients with acute ischemic stroke compared with the biomechanics of their blood samples flow, cerebral infarct volume and dynamics of neurological disorders. The results obtained revealed a new drag-reducing function of the circulating cfDNA and its important role in a regulation of blood flow hydrodynamic resistance in conditions of disturbed cerebral circulation. Moreover, our results showed a dependence of cerebral infarct volume and clinical picture dynamics on the plasma concentration of transcribed region of ribosomal repeat CpG-rich sequences (rDNA). It was established a new function of rDNA fragments circulating in the total pool cfDNK, i.e., generation of the intercommunication between blood and brain cells to induce neuroprotection in ischemic stroke.

[Stroke: the review of the problem (15 years after)].

The critical review of the key achievements in ischemic and hemorrhagic stroke of the past 15 years is presented in the article including stroke epidemiology and classification, experimental models, treatment of malignant edema after stroke, thrombolytic therapy, surgical treatment of intracranial hematomas, surgery on extracranial arteries, polyorganic insufficiency syndrome, secondary prevention of cardioembolic stroke, neuroprotection and early rehabilitation.

[Neurology at the border of centuries: achievements and prospects].

A significant role of neurology for medicine and society is caused by severity of clinical presentations and consequences of the nervous system diseases, as well as by huge economic burden related to neurological pathology. The paper presents a review of the current state and prospects for the development of socially most important fields of modern neurology, among which one can list studies of cerebrovascular, neurodegenerative, demyelinating and hereditary disorders, discovery of molecular mechanisms of their pathogenesis, and improvement of the methods of treatment, neurorehabilitation and prophylaxis on the basis of new medical technologies. An essential link between clinical and basic research in expanding the existing knowledge about the structure/functions of the brain in normal conditions and different-type pathological processes is stressed.

[Cardioneurology: the up-to-date key positions and the future prospects].

The up-to-date key positions and the future prospects of cardioneurology were analyzed. The wide range of questions of cardioneurology was represented and the necessity of the interdisciplinary approach to the diagnostics, treating and prevention of the cerebrovascular diseases were proved. It was pointed that the studied problems are the priority directions in angioneurology and have great social and clinical importance.

[Resistance to antiplatelet drugs in patients with cerebrovascular disorders].

This review concerns clinical and laboratory resistance to antiplatelet drugs (aspirin and clopidogrel) in patients with cerebrovascular disorders. Results of certain clinical trials showed that laboratory resistance to antiaggregants is associated with recurrent thromboembolic vascular events. The commonest causes of aspirin resistance are production of arachidonic acid metabolites via the lipoxygenase pathway, poor compliance with the treatment, polymorphism of the genes encoding for cyclooxygenase and glycoprotein (GP) IIb/IIIa, endothelial dysfunction. The causes of clopidogrel resistance include inadequate doses of the drug, its low absorption, poor compliance with the treatment, polymorphism of ADP receptors, GP IIb/IIIa and cytochrome P450 genes, acute coronary syndrome and stroke, metabolic syndrome. Therapeutic efficacy of antiaggregants can be improved by increasing their doses, using membranotropic agents, correcting endothelial dysfunction, etc. Because the apparent variability of antiplatelet drug resistance is currently due to the use of different test-systems by different authors, the evaluation of individual sensitivity to a given drug showing laboratory resistance and the choice of alternative therapy are thus far possible only in the framework of clinical studies. Large-scale prospective multicenter trials of antiplatelet drug resistance are needed along with research for better understanding mechanisms of individual platelet sensitivity and resistance to antiaggregants and developing efficacious methods for their correction.

[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.

[The complex energy correction of chronic brain ischemia].

Considerable disturbance of all quality of life domains that worsens social adaptation and daily living and results in an asthenic-neurotic syndrome, along with neurologic and mnestic-intellectual disturbances, was revealed in patients with chronic brain ischemia (stages I, II, III). Based on the results of the double blind placebo-controlled trial, the high clinical efficacy of cytoflavin in patients with chronic brain ischemia has been shown. The treatment with cytoflavin decreases the severity of subjective symptoms and complaints thus increasing the working ability of patients, improves balance and gait, decreases the severity of asthenic and neurotic syndromes, improves cognitive and memory functions (information storage, reasoning and attention), positively effects on quality of sleep and all aspects of quality of life, in particular, on physical activity, self-rating of health and viability as well as social activity, mental health and emotional lability.

[Results of proximal vertebral arteries endovascular interventions].

OBJECTIVE: To evaluate immediate and long-term clinical and ultrasound efficacy of proximal vertebral arteries stenting. We studied 74 subjects (age 61+/-10 years) who underwent transluminal balloon angioplasty with stenting of vertebral arteries (77 vessels). Technical success (i.e., residual stenosis < 20%) was achieved in 95% patients. No events (acute stroke, myocardial infarction, or death) were recorded during the procedure or in early postoperative period. Clinical improvement was seen in 81% patients presented with symptoms of vetebrobasilar insufficiency at the baseline (n = 52). Sixty six patients (89%) were followed up in the late postoperative period (6 to 54 months after the intervention). No events of acute stroke were recorded in the vertebrobasilar circulation. Relapse of vertebrobasilar symptoms after temporary improvement was seen in 13% patients. Stent restenosis/occlusion was diagnosed in 36% patients although no relationship was revealed between the alteration of stent patency and relapse of clinical symptoms. Restenosis correlated with initial stenosis of > or = 70% (p < 0.05) and type of stent material. Use of cobalt chromium stents was associated with 2-fold decrease of restenosis rate vs non cobalt chromium stents (24% vs 50%, respectively, p < 0.05). Therefore, stenting of proximal vertebral arteries yields good technical and clinical results. High restenosis rate is a major problem of endovascular treatment of atherosclerosis and needs further evaluation.

[Therapeutic efficiency of cytoflavine solution for infusion in emergency conditions].

The author reports results of clinical assessment of cytoflavin for injections in the treatment of different pathological condition including critical ones. It was shown that therapy reduces mortality among patients with acute disturbances of cerebral circulation to 4.8-9.6% compared with 11.7-17.1% in controls. Positive dynamic of neurologic status was documented in 79% of the patients with dyscirculatory encephalopathy versus 25% in control. Duration of comatose state decreased 1,7-fold, length of stay in resuscitation and intensive therapy wards 1.8-fold, and frequency of internal complications secondary to the effect of neurotropic poisons 2-fold. Cytoflavin corrected the level of metalloproteides and stabilized antioxidative potential of sera and cerebrospinal liquid in patient with meningitis including that of zoonotic etiology. In the period of post-narcosis rehabilitation cytoflavin restored conscience in 77% of the patients within 20 min. The drug also inhibited pathological alcohol addiction within 5 days after the onset of therapy as apparent from the improvement of intellectual-mnestic status and activization of attention. The frequency of infectious complications in patients with acute surgical abdominal pathology decreased by 5.1% and lethality by 3.6% compared with placebo group. Cytoflavin exhibited cardioprotective action in patients with myocardial infarction, during cardiosurgical intervention, and chronic brucellosis. It had hepatoprotective effect in iatrogenic hepatic conditions as well as ophthalmo- and oto-protective activity.

[Efficacy of cytoflavin in the treatment of chronic cerebral ischemia].

The author presents results of multicentre randomized studies of therapeutic efficiency of cytoflavin tablets in patients with chronic cerebral ischemia including asthenovegetative syndrome. Cytoflavin was shown to reduce clinical manifestations of asthenia, anxiety, depression, cognitive and emotional disorders and simultaneously improve quality of life. The efficiency of cytoflavin is confirmed by improved physical and psychic state of the patients, their enhanced social activity.

[Impact of antihypertensive therapy on clinical status and quality of life in patients with initial manifestations of hypertensive encephalopathy].

AIM: To study the clinical and instrumental characteristics of hypertensive encephalopathy (HE) in early stages, as well as the time course of their changes during long-term antihypertensive therapy (AHT). SUBJECTS AND METHODS: Prior to and after 9-month AHT, 57 patients aged 50-70 years who had uncomplicated grades 1-2 arterial hypertension (AH) with grades I-II HE underwent comprehensive examination comprising the studies of cognitive functions, quality of life (QL), hemorheology, and hemostasis, duplex scanning of great and intracerebral vessels, echocardiography, 24-hour blood pressure monitoring, magnetic resonance imaging. RESULTS: Early-stage HE was characterized by more cerebral complaints, higher rates of hypertensive crises, a greater degree of psychoautonomic syndrome, and worse QL. Focal brain lesions were detected in 74%; left ventricular hypertrophy (LVH) was diagnosed in 61% of cases. All the patients were observed to have cognitive dysfunctions. AHT (amlodipine, lisinopril) produced a good antihypertensive effect and substantial improvements of the patients' cognitive functions, health status, and QL. LVH regression was achieved. CONCLUSION: HE is a clinical manifestation of damage to the brain as the principal target organ in AH and should be therefore kept in mind in estimating the cardiovascular risk. The diagnosis of HE requires the use of tests to evaluate cognitive functions.

[Comparative clinical and anatomic characteristic of patients with patent foramen ovale in cryptogenic and noncryptogenic stroke].

In order to study anatomical and functional characteristics of patent foramen ovale (PFO) in patients with cryptogenic stroke and with other stroke subtypes we examined 56 stroke patients (male--35, female--21, age 46.7 +/- 16.5 years) with PFO and ischemic stroke. Diagnosis of PFO was made by transesophageal echocardiography (TEE), contrast transcranial Doppler monitoring (C-TCD), contrast transthoracic echocardiography (C-TTE). Group 1 was made up of patients with definite stroke cause (cardioembolic, lacunar, atherotrombotic) (n=40), and group 2--of patients with cryptogenic stroke (n=16). Patients in group 2 were younger than patients in group 1 (38.7 +/- 13.4 and 50.4 +/- 16.5 years, p < 0.05) and had slight neurological symptoms. These patients also more frequently had avalvular, or "window-like" anatomic types of PFO (2 [13%] and 4 [27%] patients, respectively), combination of large anatomic size (3 mm and larger) and functional level of PFO (3 degree of the right-to-left shunt by C-TCD) (p < 0.05).

Carnosine as a natural antioxidant and geroprotector: from molecular mechanisms to clinical trials.

Carnosine is a neuroprotective dipeptide consisting of beta-alanine and L-histidine. It demonstrates a number of useful features, including stimulation of brain and muscle microcirculation and a rejuvenating effect on cultured cells. Its activity is based on its antioxidant and antiglycating action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing neurodegeneration and accumulation of senile features. Recently, carnosine was successfully used to treat patients after brain stroke or patients with Parkinson disease. We conclude that carnosine can be recommended for patients under oxidative stress as a natural remedy having high efficiency and no side effects.

[Pathogenetic significance of patent foramen ovale in patients with the determined cause of ischemic insult].

The prevalence of open oval window (OOW) in patients with different types of ischemic insult and the possibility of independent pathogenetic contribution of OOW to brain injury were evaluated by examining 85 patients (mean age 53 +/- 14 yr) with cardioembolic (CES), lacunar (LS), and other subtypes of ischemic insult. CT and MRT of the head, duplex scanning of head arteries, contrast transcranial monitoring middle cerebral arteries, standard and contrast transthoracic and transoesophageal echocardiography revealed OOW in 40% of the patients. It had small anatomic and functional size and a tunnel-like shape. The presence of an interatrial shunt was unrelated to the degree of neurologic deficit, the size and location of brain injuries, the number of ischemic foci. It is concluded that OOW has no pathogenetic significance of its own and makes no contribution to brain injury in stroke-affected patients.

[Effectiveness of cerebrolysin in hypertensive supratentorial intracranial hemorrhages: results of a randomized triple blind placebo-controled study].

Cerebrolysin was administered to 38 patients with small hypertensive supratentorial intracranial hemorrhages. Cerebrolysin was used intravenous in drops in dosage of 30 ml during 14 days. High effectiveness and good tolerability of the treatment was shown. In the end of treatment, groups receiving cerebrolysin or placebo were statistically significant differed by the total NIHSS score, Bartel index and the Rankin's modified scale. Moreover, a trend to the decrease of intracranial hemorrhage volume was observed in patients treated with cerebrolysin.

[Cerebral circulation in chronic hypertensive encephalopathy].

Cerebral blood supply was studied in 123 patients with stage III hypertensive encephalopathy (HE) in the absence of occlusion of main head arteries. Duplex scanning was used to measure blood flow rate in common carotid (CCA), vertebral (VA) and medial cerebral (MCA) arteries. Cortical cerebral blood flow (CBF) was measured by single-photon emission CT using 99mTc- ceretec. Normal and stable blood flow in CCA and VA was documented at all HE stages whereas it decreased in MCA of patients with HE II-III. Cortical CBF in frontal and parietal segments in HE II-II was higher than in HE I (p < 0.05). These findings suggest impaired subcortical perfusion and correlation of the discrepancy between cortical and subcortical blood supply with the severity of HE. Leukoaraosis is an indicator of hypoperfusion.

Gene therapy of amyotrophic lateral sclerosis.

Two-year experiments were performed to evaluate the neurotrophic effect of hypoxia-inducible factors (vascular endothelial growth factor and angiogenin) expressed in recombinant human adenoviruses in amyotrophic lateral sclerosis. Randomized placebo-controlled trial demonstrated safety and good tolerability of the recombinant antiviral drugs. The life span of patients under conditions of hypoxia increased after treatment with the test drug, which was probably related to improved resistance of motoneurons. The presence of virus-neutralizing antibodies decreases the effectiveness of adenoviral vectors, which necessitates differential approach to the selection of patients and continuous monitoring of gene therapy.