Chitosan as a Modifying Component of Artificial Scaffold for Human Skin Tissue Engineering.

We compared the structure and mechanical properties of scaffolds based on pure collagen, pure chitosan, and a mixture of these polymers. The role of the composition and structure of scaffolds in the maintenance of cell functions (proliferation, differentiation, and migration) was demonstrated in two experimental models: homogeneous tissue analogues (scaffold populated by fibroblasts) and complex skin equivalents (fibroblasts and keratinocytes). In contrast to collagen scaffolds, pure chitosan inhibited the growth of fibroblasts that did not form contacts with chitosan fibers, but formed specific cellular conglomerates, spheroids, and lose their ability to synthesize natural extracellular matrix. However, the use of chitosan as an additive stimulated proliferative activity of fibroblasts on collagen, which can be associated with improvement of mechanical properties of the collagen scaffolds. The effectiveness of chitosan as an additional cross-linking agent also manifested in its ability to improve significantly the resistance of collagen scaffolds to fibroblast contraction in comparison with glutaraldehyde treatment. Polymer scaffolds (without cells) accelerated complete healing of skin wounds in vivo irrespective of their composition healing, pure chitosan sponge being most effective. We concluded that the use of chitosan as the scaffold for skin equivalents populated with skin cells is impractical, whereas it can be an effective modifier of polymer scaffolds.

[Introduction into PPPM: experience of the past and tomorrow's reality].

Health service today is on the verge of broad changes. The intensive practical application of the achievements of genomics, proteomics, metabolomics and bioinformatics has significantly deepened and continues to deepen our view of the pathological processes taking place at a level of biostructures. In the nearest future this progress will give medical practitioners the opportunity to focus on a subclinical stage of the disease, i.e. on the earliest stages of the pathological process. This will require the prediction of disease development risks, subclinical diagnostics with the precise staging of the pathological process, and, finally, the application as early as possible of targeted pharmacotherapeutic methods in order to prevent the manifestation of the disease or its progression into more severe stages. All these principles create the framework of a fundamentally new "3P" strategy in medicine: predictive, preventive and personalized medicine.

[Proteomics as a fundamental tool for subclinical screening, tests verification and assessment of applied therapy].

Proteomics is a science which studies proteins of the body, interactions of proteins and their biological functions. Today, it is an essential partner in establishing preclinical diagnosis protocols. In conjunction with other sciences such as genomics and bioinformatics it will be possible to diagnose diseases on the earliest stages before its clinical onset or to gain the dynamics of pathological processes in the body and response to drug therapy. This article discusses general aspects of proteomics as well as special ones on the basis of models of cardiac diseases and cancer.

[Development of national and international standards of population age distribution for medical statistics, health-demographic analysis and risk assessment].

The current European standard (CES) and the World population age distribution standard is widely used in medical and demographic studies, performed by international (WHO, etc.) and national organizations. The Russian Federal Service of States Statistics (RosStat) uses CES in demographic yearbooks and other publications. The standard is applied in calculation of the standardized mortality rate (SMR) of the population in different countries and territories. Risk assessment is also used CES. In the basis of the standards there has been laid the idea to assess mortality according to uniform standard, so to get possibility to compare the mortality rate of the population in different countries and regions, different genders and different calendar years. Analysis of the results of test calculations of the values of the SMR for the population of Russia and other countries with the use of current standards has revealed serious shortcomings of the latters and set up the task of improving them. A new concept of the development of standards based on the use of the concept of stable equilibrium of the age distribution of the population and survivorship function is proposed.

[Refutation of traditional views of the disease and formation of the scientific basis of pathology (17-19th centuries)].

This paper focuses on the revision of disease concepts that prevailed during the Galenism era and the formation of the scientific basis of pathology at the time of two scientific revolutions of the 17-19th centuries.

[Neuroimmunoendocrine mechanisms of regulation of reproductive function].

Modern molecular biological studies have significantly improved understanding of structural and functional organization of the female reproductive system. The paper gives a brief overview of the literature and own research on verification and expression in the endometrium and placenta of many peptides, biogenic amines, steroids, cytokines and other signalling molecules, which, acting as hormones, enzymes, inhibitors, receptors, growth factors, immunoregulatory agents, transport's and binding proteins, provide the local regulation of intercellular neuroimmunoendocrine relationships that play a key role in the mechanisms of human embryogenesis and reproduction.

[Autoregulative processes and structural principle of functional selective mobilization].

Autoregulative systems are being formed through dynamical changeability of structural components. Initial structural organization determinates possible variants of regulative connections with different probabilities resulting in a more successful formation of one system and retarding in the appearance of another one. It emphasized the domination of structural principle of functional selective mobilization during the creation of physiological, pathological and ambivalent systems (having, accordingly, adaptive, disadaptive and ambivalent significance). That's why result of system activity has not a dominant role in the process of system formation (the result, if it has adaptive significance, only promotes the consolidation of previously formed regulative connections).

[Autoimmunity and autoimmune syndrome: norm and pathology].

Multicomponent analysis of variations of serum marker antibodies is an efficacious tool for preventive (pre-clinical) diagnosis of immune disorders causing serious diseases. Successful development of this method may lead to revision of the approaches accepted in modern medicine and facilitate practical transition to the prognosis-prevention paradigm. The study of antibody spectra reflecting individual genetic and epigenetic features provides a basis for prognostication of health and pathological conditions. We believe that in most cases early diagnosis of reversible pathologic processes their further development can be arrested which provides a real opportunity to preserve health.

[Diagnostic and pathogenetic implications of the site specificity of antibody proteases in multiple sclerosis].

Disseminated sclerosis is currently regarded as a CNS autoimmune disease. One of the mechanisms behind this pathology is antibody (AB) formation. In this context, recent data on AB with proteolytic activity are of importance because they participate in selective proteolysis of myelin proteins in patients with disseminated sclerosis. This paper focuses on AB-proteases associated with disseminated sclerosis and site-specificity of antibody-mediated proteolysis of myelin basic protein. Protocol of serodiagnostic algorithm to be used in clinical practice is described.

[Current protease-antibody-based serodiagnostic tools and their use in the diagnosis of autoimmune thyroid diseases].

The purpose of the investigation was to comparatively study the possible clinicodiagnostic and clinicoprognostic value of thyroglobulin (TG) autoantibodies (anti-TG autoAB) and thyroid peroxidase (TPO) (anti-TPO autoAB) with proteolytic activity (protease-AB) and to develop additional clinicoimmunological criteria for working out a protease-AB-based laboratory serodiagnosis protocol. Sera from 240 patients with autoimmune thyroiditis (AIT), 124 with diffuse toxic goiter (DTG), and 172 with other thyroid diseases were studied. Serum from 40 clinically healthy donors served as a control. Sera were screened for anti-TG and anti-TPO autoAB by enzyme immunoassay and/or radioimmunoassay. Nonspecific proteolytic activity was determined, by incubating a highly purified AB IgG-isotype solution with nonspecific substrate (such as BSA-FITS or thyoredoxine/Trx), followed by the measurement of relative fluorescence shifts at a wavelength of 470 nm. The blood samples taken from patients with AIT or DTG and the highly purified anti-TG or anti-TRO autoAB of IgG isotype were incubated with appropriate human substrates to determine AG-specific proteolytic activity. Proteolysis products were detected by PAAG electrophoresis. An association was found between the rise in the frequency of protease AB, their catalytic activity, a tendency toward autoAB between themselves, and the degree of thyroid tissue degradation in AIT and DTG; some specific features of a serological pattern were noted in diferent dorms of AIT and DTG. For example, the prevailing autoABs have been shown to be TG-specific in AIT and TPO-specific proteases in DTG; also, the detectable catalytic activity of both autoAB in AIT is an order of magnitude higher than that in DTG. No protease ABs have been recorded in other forms of thyroid diseases in which antithyroid autoABs are also frequently detected. The screening procedure for protease AB may be considered as a highly sensitive and specific indicator test in the diagnosis and prediction of AIT and DTG, which allows one to diagnose not only within the framework of major thyroid nosological entities, but much broader, by covering a great variety of syndromal forms of pathology.

[Quantitative immunohistochemistry: optimization of analyzing the expression of signaling molecules in the myometrium].

The paper analyzes in detail various aspects of semiautomatic quantitative analysis of the results of immunohistochemical reaction using the Morphology 5.0 computer program to analyze microscopic images. Various procedures for assessing the extent of expression of nuclear and cytoplastic markers are compared and a rationale is provided to choose the value of the relative area of a microimage. The authors have developed a new method for calculating the optical density of as an indicator of the intensity of expression of the marker under study, which allows one to effectively separate the study staining from the baseline hematoxylin staining.

[Post-infection clinico-immunologic syndrome: fundamentals of etiopathogenesis and immunogenodiagnostic strategy].

Professor Yu.M. Lopukhin, an ardent advocate of translation of scientific achievements into clinical medicine, is a founder of new scientific disciplines including clinical immunology that evolved from the fusion of new knowledge, original clinical thought, high-tech diagnostic and therapeutic modalities. Highly promising investigations into molecular pathogenetic mechanisms of various diseases, their diagnosis, and prevention make up a most important aspect of his scientific work. The progress of chronic recurring infectious diseases (CRID) is closely related to the associated immune disorders, e.g. post-infection clinico-immunologic syndrome (PIKIS) that reflects the character and severity of disturbances of immune homeostasis. This syndrome associated with CRID is as a rule provoked by infectious agents of different nature, immunopathologic processes inherent in individual patients, specific clinical course ofCRID or inadequate application of antimicrobial medicines. Three forms of PIKIS are described in this paper: (1) post-infection secondary immunodeficiency syndrome:, (2) post-infection autoimmune syndrome, (3) combination of the two.

[Regulation of human dendrite cells' physiological functions with the recombinant heat shock protein Hsp70].

Reference literature review. The dendrite cells (DC) are the most important antigen-representing cells of the organism. They are the target for various vaccines, and on the basis of the DC cellular anti-tumour and anti-viral vaccines (DC vaccines) have been developed. At the same time, the DC can be a convenient model for studying activity and action mechanisms of different immune-therapeutic preparations. One of the aspects of the DC use optimization for induction of antigen-specific immune response might involve use of the heat shock proteins (Hsp), the Hsp70 in particular. This protein can be used for administration of protein antigens into the DC and for regulation of the DC activity. Knowledge of the DC physiology and specifics of interrelationship among the Hsp70 and its complexes with the DC antigens of different differentiation degree is an important aspect for implementation of these ideas. Human Hsp70 has been shown both to bring antigens to the DC and to regulate activity of the DC as well as to optimize induction of antigen-specific cellular immune response.

[Antithyroid antibodies of varying specificity in the pathogenesis and diagnosis of autoimmune thyroid diseases].

AIM: To compare the possible pathogenetic and clinicodiagnostic value of antithyroid autoantibodies (autoAB) different in specificity, such as monospecific ones to thyroglobulin and thyroid peroxidase (anti-TG and anti-TPO autoAB) and bispecific ones to thyroglobulin and thyroid peroxidase simultaneously (anti-TGPO autoAB), in patients with autoimmune thyroid diseases. MATERIALS AND METHODS: The sera from 240 patients with autoimmune thyroiditis (AIT) and from 124 with diffuse toxic goiter (DTG) were examined. The sera from 40 healthy donors served as a control. The sera were screened for anti-TG and anti-TPO autoAB, anti-TGPO autoAB, by employing enzyme immunoassay and/or radioimmunoassay. The results were statistically processed using the variation statistics-based programs. RESULTS: The specific features of an autoantigenic component to thyroid tissues were found in the sera of patients with AIT and DTG. An association was established between the progression of disease and the phasic change of autoAB populations or their combinations. CONCLUSION: The procedure for evaluating seropositivity for antithyroid autoAB, which is referred to as non-invasive studies, can be considered as a criterion test in the diagnosis and prediction of the course of AIT and DTG.

[From the history of the 19th century pathology. Pathological anatomy and pathology in the first half of the 19th century].

The paper analyzes the first half of the 19th century collective notions on disease as the event that is alien to the human body (which is embodied as a living being), which occurs and develops in accordance with its own laws differing from the laws of human vital functions; on the causes and essence of diseases and the methods of their study. It also shows a place of human pathology in the structure of medical knowledge of that time and its role in the investigation of diseases.

[Neuroimmunoendocrine mechanisms of aging].

The review discusses in detail the mechanisms of aging from the position of common signaling molecules produced in three regulatory systems: the nervous, endocrine and immune ones. It is shown that the neuroimmunoendocrine hormonal regulation of homeostasis plays the important role in the complex chain of processes that lead to aging of cells, tissues, organs and body as a whole. Particular attention is paid to morpho-functional involution of nervous, endocrine and immune systems, which is accompanied by a breach of elaborate signaling molecules. Detailed analysis and further development of integrated molecular commonality of views on the regulatory systems of both the central and especially local levels, opens vast new opportunities for deepening knowledge of the mechanisms of aging, as well as for the prevention, diagnosis and treatment of diseases associated with aging, in which pathogenesis the discoordination of neuro-immuno-endocrine signaling mechanisms plays an important role.