Altered serum levels of neuronal proteins and antibodies to them in occupational diseases of the nervous system.

Aclinical and immunological examination of men with occupational pathology, including vibration disease (VD), occupational sensorineural hearing loss (SHL), and chronic mercury intoxication (CMI), was carried out. The comparison group consisted of men comparable in age and total work experience. Serum concentrations of neurotrophins (S100ß, MBP, BDNF) and antibodies (ABs) to S100ß and MBP proteins were determined by enzyme-linked immunosorbent assay. An increase in the level of the S100ß protein was shown in CMI, VD, and a tendency for its increase was found in SHL. In parallel, an increase in AB to the S100ß protein in VD and SHL and a decrease in AB in CMI were noted. A comparative assessment of MBP levels indicated a pronounced increase in its serum concentrations in patients with CMI and VD versus the comparison group. At the same time, an increase in the level of serum ABs to MBP in individuals with VD and SHL, and a decrease in patients with CMI were noted. In patients with CMI, a significant decrease in the BDNF concentration was found, while in SHL and VD, no statistically significant differences were found in comparison with the comparison group. The results obtained confirm importance of assessing serum concentrations of neurotrophic proteins and ABs to them in the case of occupational damage to the nervous system caused by exposure to physical and chemical factors.

[Assessment of the population and subpopulation composition of lymphocytes and their relationship in patients with sensorineural hearing loss]. / Otsenka populyatsionnogo i subpopulyatsionnogo sostava limfotsitov i ikh vzaimootnosheniya u patsientov s neirosensornoi tugoukhost'yu.

Study of the role of the phenotypic composition of lymphocytes, shifts in which can cause the development of various pathological processes, including sensorineural hearing loss, is an important area of modern research. Purpose of the study. To study the population and subpopulation composition of lymphocytes and their intercellular cooperation in persons with occupational sensorineural hearing loss. MATERIAL AND METHODS: Phenotyping of blood lymphocytes (CD3+, CD4+, CD8+, CD9+, CD16+, CD20+, CD21+, CD23+, CD25+, CD95+) was performed by indirect immunofluorescence. RESULTS: Individuals with sensorineural hearing loss were found to have hyperactivation in both T- and B-cell links immunity. CONCLUSIONS: The revealed changes indicate a violation of immunoregulation through factors of intercellular cooperation, and the established relationships between populations and subpopulations of lymphocytes indicate increased activity components of the immune system, their important role in the implementation of the immune response in persons with sensorineural hearing loss.

[Comparative characteristics of cytokine and IgE levels in patients with bronchial asthma of professional and non-professional genesis]. / Sravnitel'naia kharakteristika tsitokinov i IgE u patsientov s bronkhial'noi astmoi professional'nogo i neprofessional'nogo geneza.

A comparative evaluation of serum concentrations of cytokines and IgE production in patients with occupational bronchial asthma (BA) caused by exposure to the toxic-dust factor of the aluminum industry and patients with asthma of unprofessional genesis was carried out. A more pronounced pro-inflammatory response has been found in patients with occupational BA characterized by hyperproduction of IL-1b, IL-8. While for persons with non-professional asthma, a decrease in IL-1b, IL-5, IL-10 is characteristic. The common pattern of the detected changes in the patients of both groups consists in an increase in the production of IgE (6 times in patients with occupational BA and 8.9 times with non-occupational asthma) and a decrease in serum concentrations of TNF-a. Various cytokine manifestations in occupational and unprofessional BA may be associated with different etiopathogenetic mechanisms of disturbance of intra-immune regulation, and also confirms the professional conditionality of the revealed changes in patients with BA who work in the aluminum industry.

[Role ofneuroautoimmune integration in pathogenesis of vibration disease].

Clinical immunologic and electroneuromyographic examination covered patients with vibration disease. Registered- demyelination disorders on lower and upper limbs in vibration disease patients were associated with neurochemical changes in special neural structures (OBM, S-100 protein, DNA, AH-R, DA-R, Ser-R, GAMK-R). Direct proof of demyelination disorders in vibration disease patients are reliable correlation between levels of antibodies to OBM and conduction velocity in distal part of median nerve, in ulnar nerve from elbow bend and lower third of arm, and ulnar residual latency. Diagnosed relations between levels of antibodies to regulatory proteins in nervous tissue (antibodies to OBM and to S-100 protein), neurotransmitters (antibodies to AH-R, DA-R, Ser-R, GAMK-R) and functional parameters of nervous system prove important role of autoimmune reactions in vibration disease pathogenesis.

[Mechanisms underlying changes in state of central nervous system pathways under exposure to metallic mercury].

The authors revealed mercury role in pathologic changes of central mechanisms underlying cerebral circulation in metabolic circle, associated with changes in central afferent pathways in thalamic region. Relationship was established between intensity of the diagnosed affect and changes in levels of antibodies to proteins S-100, general myeline protein, myeline-associated glycoprotein - that can indicate general neurodegeneration process. Antibodies level can serve as a marker of demyelination intensity in central pathways under exposure to neurotoxicants.

[The pre-nosologic diagnostic of vibration disease.]

The vibration disease occupies one of leading places among occupational diseases. To decrease vibration pathology and to diminish number of cases of disability an early pre-clinical detection of harmful effect of vibration on organism of worker is needed. The purpose of study is to develop mode of diagnostic of early indications of health disorders of working individuals under local vibration impact. The immune enzyme technique was applied to immunologically examine 40 males workers in contact with local vibration. In workers with pre-clinical indications of health disorders due to effect of vibration alterations were established concerning content of immunoglobulins and cytokines characterized by lowering of concentrations of IgA, IgM, TNFα and also increasing of production of pro-inflammatory cytokine IL-1ß and anti-inflammatory cytokine IL-4. The increasing of serum concentrations of neuro-specific protein S-100ß is established. The proposed mode permits detecting early indications of health disorders in workers contacting with local vibration in condition of applying minimal number of the most informative diagnostic indices that promotes decreasing of volume of clinical analyses.

[Variability of some humoral immunity parameters in workers ofvarious industries in East Siberia].

Based on examination of workers exposed to various occupational factors in major industrial enterprises, the authors present results of comparative evaluation of some humoral immunity parameters. According to the study, Ig A, M and G are possible as available indicators in evaluation of functional resources being major risk factors for occupational health. Timely diagnosis and analysis of risk factors help to improve methodology of work groups certification in industrial enterprises, specification of innovation diagnostic tools and rehabilitation of working population.

[The evaluation of immunoregulatory markers in the course of neurointoxication by mercury over the post-exposure period].

There was executed the examination of patients with occupational chronic mercury intoxication in the post-exposure period after the exposure to metallic mercury vapor. 47 persons with an established diagnosis of chronic mercury intoxication (HMI) passed the laboratory and immunological examination in the period of exposure to metallic mercury vapor in a production environment. The average age of men accounted for 49.2±1.2 years. The experience of work in hazardous working conditions amounted of 21.65±1.61 years (1 observation). All these same cases were observed in the institute clinic again after 5 years (2 observation) and 10 years (3 observation). A control group of healthy men consisted of 47 cases included persons of representative both age and general work experience, without a professional route of contact with hazardous substances. The level of such cytokines as IL-1ß, IL-2, IL-4, IL-6, TNF-a, INF-y and neurotropic IgG class antibodies directed to proteins of the nervous tissue (NF-200, GFAP, MBP, B-dependent Ca-channel, Glu-R, DA-R, R-GABA, Ser-R, R-Chol, DNA, B2GP) in serum were determined by enzyme linked immunosorbent assay. There was established the gain in the imbalance of inflammatory mediators and production ofneural antibodies in dynamics after the termination of the production in conditions of metallic mercury vapors. Revealed features of the regulatory relationship between the level of cytokines and the severity of the autoimmune process were shown to contribute to the maintenance and progression of neurodegenerative processes. There was recommended the identification of immunoregulatory markers (IL-1ß, IL-4, TNF-a, NF-AT to 200, GFAP, S-100) as an additional criteria for the diagnosis of health disorders in operating and monitoring the course of the progredient professional mercury intoxication.

[The Impact of Industrial Vibration on Level of Antibodies to Regulatory Proteins of Nervous Tissue.]

The characteristic peculiarities in changing the levels of autoantibodies (AB) to the regulatory proteins of the nervous tissue have been revealed in the workers with a long-term working period and in the patients with Vibration-induced disease (VID). The levels of AB to MPM, Ser-R and ß2GP were higher than the border of physiological level and the levels of AB to proteins GFAP and S-100 were lower than a physiological level in the workers with a long-term working period and in the patients with VID. Thereto, the higher levels of AB to GAMK-R were revealed in the patients with VID 2 times as often and 4 times as often compared with the workers with a long-term working period. The changes in the content of AB to the regulatory proteins of the nervous tissue may, most probably, testify the sano- and pathogenesis changes in the functions of the immune system. The changes in the content of AB in the workers with a long-term working period without signs of health disorders due to exposure to vibration have allowed to state the starting changes and the already manifested pathological processes of a definite localization in the nervous tissue stipulated with a long-term exposure to vibration in the patients with VID.

[FEATURES OF CHANGES IN THE IMMUNE REACTIVITY IN EMPLOYEES IN MODERN PRODUCTION OF SULPHATE CELLULOSE].

There are reported changes in the indices of the immunoreactivity of the body in employees in modern productions of sulphate cellulose in dependence on the specificity of exposing factors of the production environment. At that the main adverse factor affecting the state of the immune reactivity of workers was found to be is air pollution of the working area with methyl-sulfur compounds in the pulping process, with chlorine and chlorine dioxide--in the process of bleaching, lime and limestone dust--in the process of caustic regeneration. There were shown differences in the character and severity of the immune response to the impact of different chemical compounds. The exertion of protective immune mechanisms is most pronounced in workers employed in the process of boiling and bleaching, in whom there were revealed significant changes in humoral compartment of immunity (pronounced inhibition of the IgA synthesis, which plays an important role in the state of broncho-pulmonary immunity). At the same time, the inhibition of the functional activity of phagocytic neutrophils was the most significant in workers who was experienced to the exposure to lime and limestone dust, testifying about the depression of nonspecific mechanisms of anti-infectious protection. The revealed changes in the immune system are the basis for the formation in workers certain health disorders, mainly with broncho-pulmonary pathology.

[ASSESSMENT OF THE CYTOKINE STATUS IN EMPLOYEES IN CONDITIONS OF CHRONIC EXPOSURE TO VINYL CHLORIDE].

In the article there are presented the results of the evaluation of cytokine profile in males working in the production of vinyl chloride (trained workers without signs of disorders of the neuropsychic status and persons with early signs of neurointoxication with vinyl chloride, characterized by asthenic (emotional lability) disorder with the autonomic dysfunction). There are established differences of pro- and anti-inflammatory responses in workers in dependence on the severity of disorders of the neuropsychic status. The most pronounced imbalance of cytokines was in workers with initial manifestations of neurointoxication with vinyl chloride. The increase in the concentration of pro-inflammatory cytokines (IL-1ß, IL-8, TNF-α) in trained employees without signs of disorders of the neuropsychic status is the one of the early and sensitive indices characterizing the formation ofthe body's resistance to exposure of adverse factors of production.

[On theory of sensory conflict under exposure to physical factors: main principles and concepts of formation].

The article presents results of longstanding studies on influence of occupational physical factors on workers health. Experimental and nature studies helped to justify basic concepts of sensory conflict theory, a trigger of occupational disease formation. Patients having occupational disease present disorders of cortex-subcortex relationships on diencephal level, central and peripheral regulatory mechanisms, central sensory mechanisms participation in pathologic processes development, changes in vegetative regulation on cerebral level, demyelination and axon demyelination changes in peripheral nerves of upper and lower limbs. Findings are also changes in central nervous, peripheral nervous systems, endocrine, immune systems, severe emotional negative strain and high level of nervous system excitation, perivascular edema in brain cortex of experimental animals. Based on key principles of the theory, the authors specified and tested new methods of treatment and prevention of occupational diseases caused by physical factors, aimed to unblock the sensory conflict.

[Diagnostic value of neuronal auto-antibodies and neurodegeneration of central conduction tracts in exposure to metallic mercury vapors].

Stationary medical examination covered chemical production workers (47 individuals) with long length of service, exposed to metallic mercury vapors, and patients in remote stage of chronic mercury intoxication (51 individuals). The examination included registration of somatosensory evoked potentials and levels of neuronal antibodies. Analysis of results helped to reveal relationship between intensity of structural disorders involving central afferent conduction tracts and changes in levels of auto-antibodies to S-100 proteins, general myelin protein, myelin-associated glycoprotein--that can indicate general neurodegeneration process in central structures. Level of neuronal antibodies can serve as a unique marker of demyelination intensity of central conduction tracts under exposure to neurotoxic chemicals and considerably decrease cost of examination during regular medical checkup.

[Neuroimmune endocrine relationships under exposure to local vibration in workers].

The studies prove that local vibration in workers alters parameters of immune, nervous, endocrine systems interconnected and demonstrating pathologic process degree. Findings are that workers with long length of service, having no health disorders, increased CNTF level is associated with high TSH, increased IgG level is connected with ACTH growth. In vibration disease, increase of neurospecific protein S-100ß is associatedwith lower level of T4. Increase of anti-inflammatory IL-4 is accompanied by high level of T3--that can prove disbalance in main regulatory systems (immune, nervous, endocrine).

[Occupational neurointoxications: patterns and mechanisms of formation].

The article covers results of long-standing study of clinical features of occupational neurointoxications in late period, and mechanisms underlying nervous system disorders in individuals working under long exposure to neurotoxic chemicals and in late period of occupational intoxications. With modern neurophysiologic, neuropsychologic, immunologic and biochemical diagnostic methods, the authors specified early manifestations of occupational disorders. Translation patterns of neurointoxications are specified.

[The role of neurotrophic factors in formation of vibration disease].

The authors studied serum levels of neurotrophic factors (brain-derived neurotrophic factor BDNF and ciliary neurotrophic factor CNTF) in workers exposed to vibration (workers with long length of service and without health disorders caused by vibration, patients with occupational limbs polyneuropathy, and vibration disease patients). Findings are that occupational vibration induces increased BDNF and CNTF serum levels in all groups examined. Increased levels of neurotrophic factors at early stages of pathologic process indicate their protective action, action of compensatory protective mechanisms. However, high levels of BDNF and CNTF in vibration disease may point to neurodestructive processes in nervous system.

[The antibodies to neurohormonal anti-genes as a criterion of early diagnostic and neurointoxication in workers of chemical enterprises].

The examination was applied to enterprise workers laboring in conditions of vinyl chloride (79 patients), caustic soda (24 patients) and 10 patients with professional chronic mercury intoxication. The differences are established concerning manifestation of autoimmune reactions of personnel working in conditions of chronic effecting of vinyl chloride distinct of parameters characterizing autoimmune reactions of personnel working under impact of another neuro-toxicants (vapors of metallic mercury). The increasing of auto-antibodies to MAG was detected in healthy personnel and increasing of concentrations of auto-antibodies to protein S-100 and DNA was detected in personnel with initial manifestations of neuro-intoxication. These occurrences testify availability, of different mechanisms underlying formation of neurological disorders. The study data confirms involvement of auto-antibodies to neuronal antigens into derangement of neural activity in personnel working in conditions of effect of vinyl chloride and vapors of metallic mercury. Hence, the new possibilities are opened in studying pathogenesis of occupational neuro-intoxications. The detection of auto-antibodies to proteins of neural tissue can be recommended as a criterion of early identification of damage of neural system in personnel working in conditions of chemical industry.

[Detection of disordered immune responses to the chronic effects of vinyl chloride in the organism (clinical and experimental study)].

This paper considers the features of disorders of immunity in chronic exposure to vinyl chloride at work and in experimental animals. It is shown that one of the earliest and most sensitive indicators of the formation of the resistance of the organism employed in the manufacture of vinyl chloride, are: IgM, IL-1beta, TNF-alpha, autoantibodies to neurospecific proteins (S-100, Vd-Ca channels and DNA).

[Topical problems of occupational allergic diseases nowadays].

The article covers materials on occupational allergic diseases prevalence in variable economic branches of Baikal area, if compared to the values in Russian Federation in general. The authors defined major etiologic factors resulting in allergic diseases, demonstrated that immune suppression is a major concept in occupational skin and respiratory system diseases, revealed immune response peculiarities in accordance with acting occupational allergen type.

[Toxic encephalopathies in distant post-contact period of occupational neurointoxications (clinical and experimental studies)].

The article covers results of long-standing research on clinical peculiarities and course of toxic encephalopathy in distant period of occupational neurointoxications, on main concepts and pathogenetic steps of formation and progress of toxic encephalopathy. Through investigation covered firemen after exposure to complex of toxic chemicals and patients in post-contact period of chronic mercury intoxication. Modelling of chronic inhalation of metallic mercury vapors was performed.