Vol 9, No 4 (2009)

In the article are reflected the basic landmarks of the scientific work of the outstanding scientist academician RAMS В. I. Tkachenko. As a result of the numerous studies, executed under his management, is given experimental substantiation and theoretical generalization of the active role of organ venous vessels in the formation of the venous return of the blood to the heart and in the regulation of the postcapillary resistance, which determines the pressure level in the capillary vascular bed. It is established that the main distinctive special feature of venous vessels in comparison with the arterial is the fact that they have two clearly expressed functions, capacitive and resistive, whereas only resistive function is inherent in arterial vessels. The hypothesis about the multiple-contour regulation of venous vessels, which has the central and peripheral components, which switch on neurohumoral and biophysical mechanisms, is experimentally substantiated, proposed the functional classification of the blood circulatory system instead of the existed anatomical track layout of the blood circulation. Investigations conducted under B.I. Tkachenko management enabled to advance conception of the double adrenergic control of cholinergic neurons in the enteric nervous system.

The method of tissue microarrays (TMA), invented by H. Battifora [1], was developing actively and modernized during last 20 years. Many aspects of this method have been studied: validation of the results of TMA technology to the results of the standard research methods, the expenses of TMA creation, variants of the estimation of the results of TMA research, tissue antigenicity preservation etc [4, 5,17]. Recently research of paraffin tissue banks in the aim of retrospective search for new tumor markers was considered as «a titanic work». Today TMA method makes this work a reality [12]. The authors of the present publication have used TMA method for studying of malignant gynecologic tumors in big cohorts of patients. High-throughput, estimated in practice, an opportunity of the fast standardized analyses of numerous patients for various biomarkers, economy and adequacy of TMA method allow to recommend this method for practical use. Application of TMA method in clinical histology expands the diagnostic opportunities for different kinds of pathology essentially and promotes the foundation of predictive medicine [14]. The speed with which new prognostic factors, defining the modality of therapy, are generated and transferred into clinical practice, demands the new methodological approaches enabling real-time or retrospective estimation of these clinically significant factors in numerous patients. Wide use ofTMA method will become an integrative part of work for scientific and routine clinical research in future.

We have synthesized superparamagnetic iron particles (SIP) and developed direct non-covalent DNA immobilization method for subsequent magnetic field guided targeting of SIP-DNA complex into rodent tissue and tumor cells. In vitro transcription experiments have revealed functional activity of immobilized DNA template - highly efficient synthesis of full-size RNA transcript (1.8 Kb) of cloned XEF gene. Animal experiments have demonstrated external magnetic field-guided delivery of SIP-immobilized expression vector with human PSA cDNA into rodent tissues. RT-PCR data clear indicate that expression of human PSA transgene was restricted by targeted rodent tissues only. We propose that SIP is an useful tool for targeted delivery of therapeutic nucleic acids including DNA-vaccines into normal and tumor tissues.

A method of computer modelling of the facial skeletal structures and normalization of speech and breathe function was worked out. Effective methods of facial structures osteotomy and rational ways of bone segments fixation were proposed. General conclusion of complex reabilitation of 557 patients was made.

Genotyping and molecular typing of microorganisms are principal methodological directions of modern molecular epidemiology. Some results of basic and applied studies of St. Petersburg Pasteur Institute in the field of molecular epidemiology are presented in this article. Different methods were used successfully - complete and limited gene sequencing, restriction fragments length polymorphism (RFLP) analysis, spoligotyping, variable number tandem repeats (VNTR) typing, resistotyping and others. New data on population structure and dominating genotypes of Mycobacterium tuberculosis, Corynebacterium diphtheriae, Helicobacter pylori as well as hepatitis А, В and С viruses, human papilloma viruses that circulate in Russia, in the North-Western Region and in St. Petersburg were obtained. Genetic divergence of rubella virus population and vaccine strains of polioviruses was detected in conditions of routine mass immunizations. Direct evidence of higher efficiency of pathogens genotyping in epidemiological diagnostics was demonstrated in comparison with traditional epidemiological investigations.

Cytokines represent a new regulatory system existing alongside with the neuroendocrine regulation and aimed for the body homeostasis regulation during pathogen invasion and tissue damage. During past three decades genes of major cytokines were cloned and biologically active recombinant analogues were synthesized. Future of the cytokine therapy is connected with the recombinant molecules obtained using modern immunobiotechnology. Several new recombinant cytokine drug forms for clinical use are developed in the State Research Institute of Highly Pure Biopreparations, including that of interferon alpha 2b, mterleukin-1 beta and interleukin-1 receptor antagonist. Among them human recombinant interleukin-1 beta (Betaleukin) is registered for clinical use only in Russia. New IL-1 drug forms include ointments, geles, biodegradable sponges for therapy of Patients with burns, infected wounds, trophic ulcers. Use of IL-1 ointment for trophic ulcers therapy in patients with diabetes e to high healing efficacy and allowed to avoid amputation. Recombinant interferon alpha aerosol drug form is used for the erapy of patients with acute viral respiratory infections including influenza. Aerosolized interferon application decreased ness duration for 2-3 days.This clinical result could give very big economical effect in the whole country. In general topical cytokine application has several advantages including high local drug concentration in the desired organ, and absence of systemic adverse effects. Nowadays cytokines are widely used for the therapy of infectious diseases, immunodeficiency and activ t^ FUrt' 1er development of this therapeutic direction will give new highly effective drugs with enhanced pharmacological

The objective of this study was to develop a new approach in the endovascular treatment of critical limb ischemia based on the combined use of subintimal and intraluminal angioplasty methods. Patients with critical limb ischemia were considered suitable candidates for angioplasty if they did not show irreversible changes of the limb that would require amputation at the shin or thigh level. Between 2004 and 2008, 139 endovascular interventions were carried out in 126 patients. The procedure was technically successful in 90.5% of cases. Such a high frequency of success was achieved due to the use of standards for endovascular treatment. The frequency of major complications did not exceed 7%. The probability of absence of critical limb ischemia recurrence within one year amounted to 65%. A significant part of the patients were regarded as «unsuitable» for surgical treatment due to severe concomitant pathology, "unsatisfactory" state of the distal circulation or the presence of infection on the foot. This, together with the low life expectancy of the patients, shows the obvious advantages of combined subintimal and intraluminal angioplasty over surgical revascularization as a method of critical limb ischemia treatment.

During the analysis of results of research of various biomarkers at 50 patients with stroke, at 40 patients with brain ischemia owing to an atherosclerosis carotid arteries, at 30 patients with epilepsy syndromes, at 20 children born by mothers-addicts, the conclusion about the big clinical importance of such biomarkers, as PARK7 and nucleoside diphosphate kinase A, S-100b, Acetylpolyamine oxidase [AcPAO], S-jet fiber, GluRI an AMPA-receptor, autoantibodies (aAbs) to opiate and glutamate to receptors (type AMPA and glutamate to receptors NMDA, NmDa- autoantibodies, NR1, NR-2A-NR2D and NR3A) which help early diagnostics of pathological process, its degree of expressiveness and dynamics under the influence of therapeutic actions is made. Wide introduction in clinical practice of biomarkers is recommended: NR1, NR-2A-NR2D and NR3A, GluRI an AMPA-receptor. Literary data about genetic and biochemical markers is cited at degenerate diseases of nervous system, at Alzheimer's and Parkinson's diseases.

The pre-operative data of tumor markers, determinated with immunochemical method, studied in 144 colorectal cancer and 60 gastric cancer patients with different stages of tumor. The carcinoembrionic antigen (CEA), carbohydrate antigens CA 19-9 and CA 72-4 are analyzed for gastric cancer. The colorectal cancer patients are analyzed with CEA, CA 19-9 and CA 242.The findings compare with results of postoperative tumor stages. Established that joint increasing of any two tumor markers (CEA, CA 19-9, CA 72-4) are indicate on gastric cancer metastasis with probability 83,3%. The frequency of exposure colorectal cancer metastasis are increasing with number of increased oncomarkers and amount to 90,9% at increase three tumor markers: CEA, CA 19-9 and CA 242. The normal level of all tumor markers in colorectal cancer exclude IV stage of tumor (distant metastases) and with probability 85,7% testify to regional nodes metastases absence.