[Complex study of the rat heart at isoproterenol damage].

Introduction of isoproterenol (an agonist of beta-adrenoreceptors) to rats is one of the widespread experimental models of cardiac failure. It is caused by damage of cardiomyocytes with the subsequent development of substitutive fibrosis. The purpose of the given work was the complex characteristic of cardiac function by means of invasive and noninvasive (echocardiography and impedansometry) methods of research.

[Suppression of vascular endothelium hyperpermeability by cell-permeating peptide inhibitors of myosin light chain kinase].

Novel peptides originating from the peptide inhibitor of myosin light chain kinase, L-PIK (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys), have been studied for ability to attenuate the thrombin-induced hyperpermeability of endothelial cell monolayer in culture. Peptides [NalphaMeArg1]-Lys-Lys-Tyr-Lys-Tyr-Arg-(D)Arg8-Lys and H-Arg(NO2)Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 (designated PIK2 and PIK4, respectively) appeared to be the most effective inhibitors of endothelial cell monolayer hyperpermebility, and surpassed other known peptide inhibitors of myosin light chain kinase derived from original L-PIK. Our results validate PIK2 and PIK4 as the leading molecules for the development of novel drugs intended to counteract pathological hyperpermeability of vascular endothelium.

[Molecular physiology of the endothelium and mechanisms of vascular permeability].

Endothelium of microvessels acts as selective barrier between blood and tissues and regulates transport of substances across vascular wall. In stressful situations permeability of microvessels increases acutely and leads to edema and the loss of organ function. This review describes molecular mechanisms of maintenance, loss and recovery of endothelial barrier as well as modern approaches to pharmacologic correction of vascular hyperpermeability.

[Novel peptide inhibitors of the myosin light chain kinase suppress hyperpermeability of vascular endothelium].

The ability of novel cell-permeating peptide molecules derived from the peptide inhibitor of the myosin light chain kinase (MLCK) L-PIK (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys) to inhibit this kinase in vitro and attenuate the thrombin-induced hyperpermeability of endothelial cell monolayer in culture has been studied. It was found that the compounds [NalphaMeArg1]-L-PIK and [Cit1]-L-PIK possess the inhibitory activity towards MLCK comparable to that of L-PIK and the ability to suppress the hyperpermeability of endothelium, whereas other modifications of L-PIK were less effective. Thus, among de novo synthesized peptides, [NalphaMeArg1]-L-PIK and [Cit1]-L-PIK demonstrate the inhibitory properties of the original peptide L-PIK and additionally surpass it by stability in blood plasma.

[Rho-associated protein kinase is involved in establishing the contractile phenotype of cardiomyocytes].

It has been shown that Y-27632, an inhibitor of Rho-associated kinase, delays sarcomere assembly in rat neonatal cardiomyocytes pretreated with angiotensin II. Y-27632 affects the beat rate of cardiomyocytes; however, this effect is only observed at high cell density and, therefore, seems to be related to the formation of gap junctions between adjacent cardiomyocytes. Consistent with this suggestion, we established that Rho-associated kinase is localized in myofibrillar Z-discs of human myocardium and intercalated discs, the structures enriched in gap junctions.

[Peptide inhibitors of myosin light chain kinase. Development of peptidase resistant analogues].

Myosin light chain kinase (MLCK) is the key regulator of various forms of cell motility including endothelial and epithelial permeability in particular. One of the potential MLCK inhibitors to be used in humans is a membrane permeable peptide H-RKKYKYRRK-NH2 (L-PIK). In present work we used solid phase peptide synthesis and Fmoc-technology to produce five modifications of L-PIK.

[Health status hygienic assessment of primary military education establishment pupils].

During a comprehensive study, the investigators have made a hygienic assessment of an academic process and the actual nutrition of military school pupils, revealed the specific features of functioning of the body's major systems in adolescents at a closed primary military education establishment, studied the body's adaptive reactions to a combination of factors during study, and hygienically evaluated the pupils' health. Their health has been shown to improve at a closed education establishment according to the basic parameters of the body's functional status and nonspecific resistance, physical development. Specific recommendations are proposed to correct daily diets for pupils of primary military education establishments in order to bring the actual nutrition of cadets in compliance with the standard physiological requirements for this group of pupils.

[Myosin phosphorylation as the main way of regulating smooth muscle contractions].

Rho-kinase is a key enzyme of the receptor-dependent signal cascades and is regarded today as the most prospective target for pharmacological therapy of smooth muscle contractility disorders.

[Penetrating peptide inhibitor of the myosin light chain kinase suppresses hyperpermeability of vascular endothelium].

Nonapeptide H-Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 corresponding to a modified sequence of autoinhibitory region of myosin light chain kinase (MLCK) was synthesized from L-amino acids and from D-amino acids. Using nuclear magnetic resonance spectroscopy it has been demonstrated that D-peptide is significantly more stable in human blood plasma than its L-enantiomer. D-peptide accumulated in cultured human umbilical vein endothelial cells suppressed development of hyperpermeability in endothelial monolayer induced by thrombin addition.

[The use of statins, a new approach to the treatment of autoimmune diseases].

HMG-CoA inhibitors (statins) are widely used for the prevention of cardiovascular events and the management of hypercholesterolemia. Recently, multiple cholesterol-independent properties of statins have been discovered. The present review focuses on immunomodulatory and anti-inflammatory effects of statins and their implications for the treatment of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and psoriasis.

[Relationship between blood lipid spectrum and activity of the disease in patients with rheumatoid arthritis].

Patients with rheumatoid arthritis (RA) are at risk of cardiovascular disorders. Pathogenesis of rapidly developing atherosclerosis in RA remains to be elucidated. The aim of this study was to compare cholesterol content in serum lipoprotein subfractions in patients with RA and healthy subjects and to establish relationship between lipid profile variations, severity of the disease, and plasma levels of anti-inflammatory cytokines.

[Replacement renal therapy in complex treatment of severe acute pancreatitis].

The purpose of this study was to retrospectively analyze the efficiency of replacement renal therapy (RRT) in multimodality treatment for severe acute pancreatitis (SAP) concurrent with a systemic inflammatory response and multiple organ failure/dysfunction. The authors analyzed the results of treating 55 patients (14 women and 41 men) aged 22 to 72 years (mean 43.5 +/- 16.

[Mini-invasive technologies for the acute pancreatitis treatment].

Results of treatment of 2415 patients with acute pancreatitis, including 285 cases of the acute necrotizing pancreatitis, are analyzed. The algorithm of diagnostics and treatment of this category of patients is worked out and successfully applied. The comparative results of the acute pancreatitis treatment before (1995-1999) and after (2000-2005) introducing the algorithm to practice are analyzed.

[Hygienic risk factors of congenital malformations].

The frequency of multiple congenital malformations, central nervous system and genital malformations were found to be associated to the magnitude and duration of ecological load. Xenobiotics identified in the ambient air of a large industrial center pose an increased risk for antenatal malformations. The largest number of statistically significant correlation coefficients was established between the study variables at a delay lag of 2 years.

[Molecular mechanisms of cardiomyogenesis and perspectives of cardiomyocyte regeneration in cardiac failure].

This review analyzes the current state in investigations of molecular, genetic and cellular mechanisms of cardiac development as well as perspectives to use this knowledge for treatment of cardiac failure by means of replenishing cardiomyocytes in damaged myocardium.

[The myosin-activating protein kinases in human myocardium: localization and content].

Using the immunofluorescence approach, we have determined that the recently detected protein kinases, among which are RhoA-activated kinase, integrin-linked kinase, zipper interacting protein kinase, and death-associated protein kinase, which are capable of phosphorylating myosin, are localized in the Z-lines sarcomeres of human myocardium. Additionally, we studied the content of integrin-linked and zipper interacting protein kinases in human embryonic myocardium, as well as in normal and hypertrophic adult human heart. The content of these protein kinases in adult normal myocardium increases in comparison with the embryonic heart.

[Simvastatin effects on the disease activity and cholesterol content in blood serum lipoprotein subfractions in patients with rheumatoid arthritis].

Aim: To study activity of rheumatoid arthritis (RA) and cholesterol content in subfractions of blood serum lipoproteins in the course of simvastatin treatment.

Material And Methods: The pilot study enrolled 16 patients with active rheumatoid arthritis (RA) meeting ACR criteria. Any standard anti-RA medication in stable doses was supplemented with simvastatin in a dose 40 mg/day for 12 weeks.

[The wound healing stimulation].

The aim of the study is to work out the method of stimulation of postoperative wound healing after emergency abdominal surgery. Morphologic and morphometric studies showed that serotonin and/or NO-therapy use in the treatment of surgical laparotomic wounds furthers its healing by decreasing distrophic and inflammatory processes and favouring fibroblast proliferation, neoagiogenesis, collagen production etc. Results of 763 patients with laparotomic wounds treated with serotonin, mexidole and NO postoperatively demonstrate faster wound healing and absence of infectious suppurative complications.

Circadian variations in immune values and serum melatonin in asthmatics.

Circadian variations in the immune status and serum melatonin were studied in asthmatics during exacerbation stage before and after treatment. Deviations from the normal (donor) immunogram values at 9.00 and 21.

[Content of myosin-activating protein kinases in myocardium of patients with dilated cardiomyopathy and in the animal heart].

The skeletal myosin light chain kinase (skMLCK) was identified in human and chicken embryo myocardium but not in embryo and adult rat heart using western blotting. The content of skMLCK and myosin-activating protein kinases: RhaA-activated protein kinase (ROCK), integrin-linked protein kinase (ILK), and zipper-interacting protein kinase (ZIPK) was compared in normal human myocardium and the hearts of patients with dilated cardiomyopathy (DCM). It was demonstrated that the content of skMLCK, ROCK and ILK increases in DCM whereas the content of ZIPK decreases.

[KRP/telokin differentially regulates filament assembly and phosphorylation of light chains of non-muscle myosin II in fibroblasts].

Transgenic 3T3 fibroblasts have been generated that express either the wild-type KRP or its truncated mutant lacking the C-terminal domain, which primarily contributes to myosin binding of KRP. It was found that KRP-expressing cells display a significantly increased content of myosin filaments and a reduced level of rMLC phosphorylation, whereas the mock transfected cells or cells expressing the C-terminally truncated KRP do not. Our results suggest that (1) KRP promotes the polymerization of myosin II and reduces the rMLC phosphorylation level in cells, (2) KRP acts through direct binding to myosin II, and (3) transgenic 3T3 fibroblasts stably expressing KRP represent a useful and versatile model to study the role of myosin II filament dynamics in cell motility.

[Expression of contractile and cytoskeletal proteins in myocardium of patients with dilated cardiomyopathy.].

Dilated cardiomyopathy (DCM) is characterized by enlargement and dilation of all heart compartments associated with serious decrease of its contractile function. DCM hallmark is the combination of dystrophic and hypertrophic alterations of cardiomyocytes. Since the power output of cardiac cells is directly related to remodeling of their contractile machinery we investigated expression of selected contractile and cytoskeletal proteins in the left ventricle of DCM patients using immunoblotting.

[Results of Befnorin clinical trails in healthy volunteers].

Clinical trails of Befnorin based on the human recombinant TNF-beta elaborated at the Research Design and Technology Institute of Biologically Active Substances, "Vector" State Research Center of Virology and Biotechnology, were carried out on healthy volunteers in compliance with a decision passed by the Committee of Medical and Immunobiological Preparations, Russia's Health Ministry. Single Befnorin doses of 5-10(4) U, 10(5) U, 5-10(5) U, and 10(6) U were administered as intramuscular injections. Clinical, biochemical and immunological parameters were registered for 7 days after a single dose.