[Experimental study of the influence of disturbing factors and chaperone-like drugs on cataractogenesis].

A comparative experimental study of biomicroscopic appearance of lenses in cataracts of different genesis (age-related, ultraviolet and other radiation-induced or combined) has been performed on animals (mice). It is shown that identical lens opacification can be provoked by aging (endogenous factor), as well as ultraviolet and other radiation exposure (exogenous physical factors). The only differential sign is the severity of the damage. These factors can be arranged in the following ascending order by their damaging ability: aging --> ultraviolet --> gamma rays --> gamma rays + ultraviolet. Anti-cataract effect of a chaperone-like combined drug (N-acetylcarnosin and D-pantetin) has been studied in vivo on a "prolonged" model of induced cataract in rats. The use of the combined drug (1:1 mixture of the two peptides) in the form of ocular instillations and intraperitoneal injections helped slowing the progression of the ultraviolet-induced cataract in vivo.

[Experimental study of influence of different damaging factors on lens. Report 2. Features of microscopic lens changes].

Microscopic lens changes are studied in mice (F1C57B1XCBA) depending on age and after ultraviolet (UV), gamma-irradiation and their combination. In all animals compared to young 3-months animals nonspecific changes due to aging were revealed: microvacuoles in cytoplasm of fiber cells, flattening of epithelial cells and nuclei fragmentation, swelling and confluence of cortical layer cells in anterior and posterior subcapsular zones. In epithelial cells the following changes were noted: nuclei polymorphism, cavities in a cell layer formation of multilayered structures of fibroblast-like cells and cell desquamation. Degree of nuclei vacuolization was significantly lower in groups with gamma- and gamma+UV-irradiation but higher in a group of UV exposure. The number of cells per unit area was significantly decreased in a group of gamma-irradiation after 7 and 10 months of exposure. Aging and UV exposure caused decrease of nuclei area, whereas affect of gamma-irradiation depended on proliferative capacity of cells: size of central cells increased and of peripheral cells reduced. Specific changes were not revealed for any of the factors.

[Experimental study of influence of different damaging factors on lens. Report 1. Features of biomicroscopic changes].

Comparative study of lens biomicroscopy in cataract of different etiology (senile, ultraviolet, radioactive and combined ultraviolet- radioactive exposure) is performed in experiment on animals (mice). Lens opacification pattern was showed to be similar in aging as an endogenous factor and ultraviolet (UV) and radioactive exposure as exogenous physical factors. Specificity of these factors is expressed in degree of damage only. Depending on damaging potential the factors may be arranged in a following way (in increasing manner): aging, ultraviolet irradiation, gamma-irradiation, gamma+UV-irradiation.

[Experimental study of influence of different damaging factors on lens. Report 3. Changes of lens protein composition].

Using differential electrophoresis protein composition of lens major proteins in hybrid mice F1 (C57B1XCBA) with cataracts of different etiology (senile, ultraviolet, radioactive and combined ultraviolet-radioactive exposure) was studied Changes that may be specific for cataract caused by aging, ultraviolet and/or gamma-irradiation were not revealed in water-soluble and water-insoluble protein fractions.

[Exogenic proteins in the human exhaled breath condensate].

The analysis of the protein composition of exhaled breath to diagnose diseases of the respiratory system raises a problem of differentiation proteins of expressed in the tissues of the lungs and respiratory tract (endogenous) and got in the respiratory system from the ambient air in the process of respiration (exogenous). In this work an attempt was made to estimate a set of exhaled exogenic proteins by mass spectrometry coupled with nanoflow HPLC. Six-month isolation of healthy donors indoors with air cleaned of dust leads to removal from the spectrum of exhaled proteins of some keratins that are considered therefore to be exogenic. Non-keratin proteins may also circulate between the ambient air and human respiratory ways, but their concentration appears to be significantly lower the keratin concentrations (especially epidermis keratin). Among non-keratins dermcidin seems to be the most significant exogenic protein of exhaled air. The conclusion of the diagnostic value of exhaled proteins can be done only after careful comparison of the results of quantitative and qualitative analysis of their composition in norm and pathology for a statistically significant sample of donors.

[Comparative study of aging, UV treatment, and radiation on cataract formation].

Four randomized groups of male mice F1 (C57Black/CBA) were investigated: a) UV-irraidated (UV-A, 15 min daily during 9 months, dose 5.6 + 1.2 W/m2), b) gamma-rays irradiated (2 Gy), single, c) influence for combination of UV- and gamma-rays treatment, d) aging. The lens opacities were measured on 7th and 10th month. The expert method based on six grade scale was used for cataract measure. On 7th month the median of lens opacities were Aging group = 0; UV-irradiated group = 2.5; gamma-irradiated group = 4.75; gamma- and UV-irradiated group = 6.0. The difference between all groups was significant (p < 0.004, Kruskall-Wallis ANOVA test). The Conover post hock test has shown the significant difference for all comparison pairs (p < 0.002) with the exception of UV-irradiated group, gamma-irradiated group, gamma- and UV-irradiated group. On 10th month the lens opacities were strongly increased: Aging group = 2.5; UV-irradiated group = 5.0; gamma-irradiated group = 6.5; gamma- and UV-irradiated group = 7.5 (median). The difference between groups was significant (p < 0.0001, Kruskall-Wallis ANOVA test). The Conover post hock test has shown the significant difference for all comparison pairs (p <0.003) with the exception ofthe UV-irradiated group and gamma-irradiated group. The formation of the specific lens opacities for any group was not found. Morphology and protein composition have been investigated on 10th month. The results of morphological changes study show destructive and degenerative impairments of capsule, epithelium cells and lens fibers. However, no specific changes related to some particular actions have been found. In addition, there were no specific changes of protein composition of both water-soluble and water-insoluble fractions estimated with Differential Gel Electrophoresis technique. Obtained data mean that aging, UV-treatment, and gamma-radiation causes the similar changes of lens. It was supposed that UV-treatment or/and gamma-radiation act as an aging factor on the lens.

Structural and catalytic polymorphism of human enzymes: Novel potential platforms for biomedical diagnostics.

This review focuses on some intermediate results on the path from the gene and enzyme structure to physiological responses and personalised medicine. Bioinformatics of genetic and protein-structural polymorphisms, theoretical methods of predicting the influence of single amino acid substitutions on the structure and catalytic activity of enzymes are considered. For a large group of enzymes, interrelations between genetic modifications, structural changes of the proteins and the detected physiological and clinical manifestations are discussed. In this respect, highly productive techniques to determine the catalytic activity of an enzyme as well as non-invasive proteomic approaches are of particular interest. A non-invasive proteomic analysis using mass-spectrometric protein identification of human exhaled breath condensate and tear fluids has been chosen.