[Sympathetic Nervous System Activation in Pathogenesis of Development of Essential Hypertension and Its Role in Target-Organs Damage in Young and Middle Aged Adults: the Cardioprotective Capabilities of Bisoprolol].

The article discusses various mechanisms of developmentt and progression of arterial hypertension in young and middle aged adults. It emphasizes the predominant role of hypersympathicotonia in the development of the disease in this category of patients. Various mechanisms are considered, by means of which the increase of activity of the sympathetic nervous system leads to elevation of arterial pressure and potentiates early damage of target organs, first of all, damage of the heart. The data of numerous studies demonstrating pronounced cardioprotective effects of a highly selective representative of the class of ß-blockers bisoprolol in young and middle aged hypertensive patients are presented.

IMMUNOGENIC PROPERTIES OF RECOMBINANT MOZAIC PROTEINS BASED ON ANTIGENS NS4A AND NS4B OF HEPATITIS C VIRUS.

The aim of the study was to investigate immunogenic properties of mosaic recombinant proteins constructed on the data of hepatitis C virus NS4A and NS4B antigens. Four mosaic recombinant proteins, containing the T and B epitopes of the NS4A and NS4B antigens, were created by genetic engineering methods in the E. coli system. To enhance the immune response they were linked in different variations to the nucleotide sequences of murine interleukin-2 (IL-2), the Neisseria meningiditis lipopeptide, and the T helper epitope of the core protein of hepatitis C virus. The immunogenic properties of these recombinant proteins were analyzed by immunoblotting, ELISA and ELISpot using sera from immunized mice and patients infected with hepatitis C virus. Recombinant proteins specifically reacted with the sera of immunized mice and infected patients in immunoblotting. According to the ELISA data, the predominant formation of antibodies to NS4B was observed when mice were immunized with the recombinant proteins containing both antigens. Analysis of gamma-interferon production by T-lymphocytes upon contact with activated dendritic cells showed in ELISpot that the maximum production of this cytokine was detected when adjuvant components were located at the N- and C-ends of the recombinant protein. The highest level of gamma-interferon production during stimulation with this drug was detected in lymphocytes from the bone marrow and lymph nodes. The recombinant protein containing the T and B epitopes of NS4A and NS4B, murine IL-2 and the lipopeptide Neisseria meningiditis had the greatest immunostimulate effect among the four constructions. This recombinant protein formed nanoparticles of 100-120 nm in size.

Investigation of the effects of GABA receptor agonists in the differentiation of human induced pluripotent stem cells into dopaminergic neurons.

The influence of GABA receptor agonists on the terminal differentiation in vitro of dopaminergic (DA) neurons derived from IPS cells was investigated. GABA-A agonist muscimol induced transient elevation of intracellular Ca2+ level ([Ca2+] i ) in the investigated cells at days 5 to 21 of differentiation. Differentiation of cells in the presence of muscimol reduced tyrosine hydroxylase expression. Thus, the presence of active GABA-A receptors, associated with phenotype determination via Ca2+-signalling was demonstrated in differentiating human DA neurons.

[Renoprotecion With Metabolic Syndrome: the Possibility of Receptor Agonist Imidazoline Moxonidine].

The article is devoted to the of prevalence, diagnosis, and prognostic significance of renal damage in metabolic syndrome. The pathogenetic mechanisms of development and progression of chronic kidney disease in individuals with obesity, including the role of increased activity of the sympathetic nervous system is discussed. Approaches to the choice of antihypertensive drugs with an emphasis on metabolic and renal protection properties are given. The advantages of imidazoline receptors in neuroprotective of moxonidine in patients with arterial hypertension, metabolic syndrome, and diabetes mellitus is discussed in detail. number of mechanisms of renal protection actions of the agonists of imidazoline receptors is described.

[The Results of Long-Term Observation of Patients Who Participated in the ADVANCE Trial].

We present in this article data on the prevalence and risk of complications in patients with diabetes and hypertension. From the standpoint of current guidelines on the management of arterial hypertension we consider problems of target blood pressure levels and choice of antihypertensive drugs in patients with diabetes, including those with diabetic nephropathy. We also present results of long-term observation of participants of the ADVANCE trial that have shown that reduction of mortality achieved because of antihypertensive therapy in the randomized study persisted throughout follow-up. Discussion of possible mechanisms of this phenomenon and the advantages of fixed perindopril/indapamide combination is presented as well.

[Hormonal and Metabolic Differences in Patients With Coronary Artery Disease].

OBJECTIVE: To prove the involvement of the autonomic nervous system in the formation of thrombotic status of the patients. 24 patients with myocardial infarction were enrolled in the study. Catecholamines levels were compared duing pain episodes and at rest. Patients were divided in to 2 groups according to the level of norepinephrine during the pain episode: Group 1-12 persons with the level of norepinephrine more than 500 pg/ml, and group 2-12 persons with a level below 500 pg/ml. Patients in group 1 the level of beta thromboglobulin and thromboxane were elevated, as well as there are changes of cAMP and cGMP, indicating increased thrombogenic activity. Particular attention was paid to the 8 patients in Group 1, in which the level of norepinephrine is maintained above 500 pg/ml both during pain and at rest (disseminated intravascular coagulation).

[Value of Fatty acids in formation of thrombotic status in patients with ischemic heart disease].

Interrelation between fatty acids and platelet aggregation has been a subject of interest for cardiologists in the terms of thrombogenic status. In order to study this problem we observed 42 patients with ischemic heart disease and 30 healthy persons. In patients we found elevation of arachidonic acid and lowering of docosahexaenic acid levels. Hypoxemic assay revealed in these patients lowering of prostacyclin and antithrombin III levels. In the pathogenesis of disturbances of platelet aggregation in patients with ischemic heart disease alteration of structure of platelets with increased quantity of phosphatidyl ethanolamine and corresponding change of thrombocyte asymmetry resulted in conformational reorganization of proteins and lipids.

[Blood viscosity in patients with ischemic heart disease].

AIM: To elucidate relation of blood viscosity to development of a hypoxic state of microcirculation in patients with ischemic heart disease (IHD). MATERIAL AND METHODS: We examined 42 patients with postmyocardial infarction cardiosclerosis and 30 healthy persons (control group). Measurements were made by rotatory viscometer at shear rates 1 - 10 s(-1). RESULTS: In patients with IHD we found increased blood viscosity and lowering of blood fluidity limit. Pathogenesis of increased blood viscosity in patients with IHD involves elevated blood fibrinogen, enhanced aggregation ability of erythrocytes, and accelerated formation of fine and large erythrocyte aggregates.

[Dynamics of morphological structures of platelets in patients with ischemic heart disease in dependence on blood levels of fatty acids].

Levels of fatty acids in platelets of ischemic heart disease (IHD) patients (n = 39) has been compared with those in healthy subjects (n = 12). Increased content of arachidonic acid and thromboxane A2 in platelets of IHD patients forms thrombogenic picture of IHD. High level of fibrinogen and decrease in heparin and antithrombin III in IHD patients facilitates formation of blood clots. Morphological examination of platelets in IHD patients has demonstrated an increase of levels of discocytes and spherocytes as well as appearance of small and large platelet-erythrocyte aggregates promoting blood slot formation.

[Pathogenesis of myocardial hypoxia in patients with metabolic syndrome].

Aims of the study were to determine main pathophysiologic mechanisms of decreased exercise tolerance in patients with metabolic syndrome (MS); to prove the state of hypoxemia by ergospirometry in patients with MS; to reveal with the help of echocardiography lowering of functional activity of the myocardium in MS; to confirm by electron microscopic techniques the presence of perivascular and interstitial fibrosis and fatty infiltration of the myocardium in patients with MS. In the study we have observed 39 patients with MS and 12 healthy individuals. We have noted the decrease of peak oxygen consumption and carbon dioxide excretion during the ergospirometry at anaerobic threshold in patients with MS. Echocardiographic examination has proven the reduction of left ventricular ejection fraction and cardiac contractile performance. The electron microscopic techniques have shown diffuse-focal interstitial fibrosis, hypertrophy of myocardial cells and fatty infiltration of the myocardium.

[Hormonal desintegration in metabolic syndrome].

The aim of the study is to reveal hormonal disintegration in patients with metabolic syndrome (MS). The examination of 27 healthy persons and 38 patients with metabolic syndrome was performed with assistance of Clamp-test and computer tomography. The dynamics of insulin, leptin, cortisol, testosterone and estradiol levels was studied. Influence of hyperinsulinemia and insulin resistance, leptin and cortisol levels fluctuation on MS development is shown. Probable mechanisms of hormonal interaction being in the base of the pathological process are proposed. Influence of sensitivity to insulin on the activity of sympathetic nervous system and increase of arterial pressure is demonstrated.

[A case of pancreatic glucagonoma].

Neuroendocrine tumor consisting of pancreatic alpha-cells -- glucagonoma -- is a very rare finding (one case per two million people a year). This functionally active, usually malignant tumor has typical clinical manifestations. Glucagonoma syndrome is a disease that has an original clinical picture that includes necrolytic migrating erythema with secondary bullous dermatitis, glucose tolerance disorder or diabetes mellitus, weight loss, anemia, hypoaminoacidemia, venous thrombosis, and alimentary and mental disturbances. By the time diagnosis is made, 60 to 70% of glucagonomas already give metastases, and even small glucagonomas should be considered tumors with unknown malignant potential or malignant tumors. Glucagonomas grow slowly, and patients live long (the survival median is approximately 15 years). The authors describe their own observation.

[Clinical value of detection of insulin resistance in woman with metabolic syndrome].

Hyperinsulinemic and euglycemic clamp studies were done in 17 women selected from 64 postmenopausal female patients aged 46-67 years with clinical picture of metabolic syndrome, and in 7 control women. Clamp test made it possible to follow dynamics of insulin and other hormones in the process of regulation of glucose level. This method allowed to prove quantitatively the presence of resistance to insulin and hormonal disintegration in patients with metabolic syndrome. Elevation of activity of sympathoadrenal system plays an important role in the pathogenesis of hypertension in metabolic syndrome at the account of augmented sensitivity of receptor apparatus. Lowering of somatotropic hormone level in patients with metabolic syndrome is associated with disturbed somatotropic function of the hypophysis which regulates blood pressure.

[Efficacy and safety of different beta-blockers in patients with isolated systolic hypertension associated with diabetes mellitus and obstructive pulmonary diseases]. / Effektivnost' i bezopasnost' razlichnykh beta-blokatorov u patsientov s izolirovannoi sistolicheskoi gipertoniei i soputstvuiushchimi sakharnym diabetom i obstruktivnymi bolezniami legkikh.

AIM: To compare efficacy and safety of atenolol, methoprolol and bisoprolol, as the most usable beta-blockers, in patients with isolated systolic arterial hypertension (ISAH) and concomitant diabetes mellitus (DM) and/or chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Forty tow patients with ISAH and coronary heart disease, 30 patients with these diseases associated with DM and 32 patients with associated COPD were randomized into three groups. Group 1 received atenolol in a dose 25 mg twice a day, group 2--metoprolol tartrate in a dose 25-50 mg twice a day, group 3--bisoprolol in a single dose 5-10 mg/day. All the patients were examined before the treatment and in 8 weeks. Arterial pressure was assessed at 24-h monitoring (ABPM-04 unit, Mediteck, Hungary) and quality of life (QL) was estimated by DISS Disability Scale. In addition, blood glucose was measured in patients with concomitant DM, external respiration function (ERF) was studied before and after the treatment in patients with concomitant COPD. RESULTS: In all ISAH patients there was a significant fall of systolic arterial pressure and heart rate. 2 hours after intake of atenolol and methoprolol blood glucose lowered significantly in diabetics as well as peak volume expiration velocity in patients with COPD. In the bisoprolol group ERF and blood glucose in DM and COPD patients remained unchanged. Atenolol deteriorated QL by the "job" and "social life" scales, methoprolol--by the scale "job" while bisoprolol improved the above parameters. CONCLUSION: The results of bisoprolol treatment are better than those of methoprolol and atenolol treatment of hypertensive patients with concomitant DM and COPD.