[Deceleration of cataract development in rats under the action of N-acetylcarnosine and D-pantethine mixture].

The effect of a mixture of N-acetylcarnosine and D-pantethine (1 : 1, m/m) on UV-A induced cataract in rats was studied. It is shown that instillation of a 5% mixture into the eyes or intraperitoneal injections (25 or 150 mg/kg) inhibit the formation of cataracts, starting from 82nd day of the experiment (p < 0.03), after which the protective effect of the mixture significantly increases (p = 0.0003). UV-A irradiation significantly (p < 0.01) increased the content of water-insoluble proteins in the lens. The use of the mixture of N-Acetylcarnosine and D-pantethine prevented (p < 0.001) an increase in the content of water-insoluble proteins caused by UV-A irradiation. Gel permeation chromatography data showed that, in the control group, water insoluble proteins consist of 3 fractions (40 kDa, 100 - 200 kDa, and1000 kDa). UV-A irradiation reduced the amount of protein in fraction 1 and increases the amount of protein in the fractions 2 and 3. The use of the mixture of N-acetylcarnosine and D-pantethine reduced the effects of UV-A light. The authors attribute the effect of the N-acetylcarnosine and D-pantethine mixture to their chaperone-like properties.

[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.

[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.

[Study of soluble proteins of mouse crystalline lenses (normal and in cataract)]. / Issledovanie rastvorimykh belkov khrustalikov myshei v norme i pri katarakte.

The water-soluble proteins from mice lenses (normal and cataract lenses) were investigated by methods of absorption spectrophotometry and kinetics of UV-induced radical decay. General characteristic of internal structure of extraction proteins was investigated by recombination kinetic method. It was shown that concentration of water-soluble proteins lowered ten times in lenses of mature cataract, i. e. 90% protein molecules were connected in lenses of mature cataract.

[The action of émoksipin on the basal activity of cyclic nucleotide phosphodiesterase and on the late receptor potential of the isolated retina]. / Deistvie émoksipina na bazal'nuiu aktivnost' fosfodiésterazy tsiklicheskikh nukleotidov i pozdnii retseptornyi potentsial isolirovannoi setchatki.

The influence of emoxypin (derivate of 3-hydroxypyridine) upon the late receptor potential (LRP) and activity of the cyclic 3',5'-nucleotide phosphodiesterase (PDE) have been investigated. The inhibition of PDE and increase of the amplitude of LPR have been shown. The curve (RP as a function of the stimulus light intensity) was moved towards the lesser lighting and the time of the achievement of the maximum was increased. Thus, emoxypin produces an effect on the LRP like classical inhibitors of PDE. It is suggested that increase of the functional activity of the retinae upon the influence of emoxypin in caused by the influence of the one towards the system of the cyclic nucleotides.

[Inhibition of cyclic nucleotide phosphodiesterase from the rod outer segments of the frog retina by 3-hydroxypyridine]. / Ingibirovanie fosfodiésterazy tsiklicheskikh nukleotidov iz naruzhnykh segmentov palochek setchatki liagushki 3-oksipiridinami.

The influence of 8 analogues of 3-hydroxypyridine upon the phosphodiesterase of rod outer segments of frog retinae has been investigated. It has been shown that the analogues of 3-hydroxypyridine inhibit the enzeme reversely and noncompetitively in case of hydrolysis towards the cAMP and cGMP. The natural analogues of 3-hydroxypyridine (pyridoxol, pyridoxale, pyridoxale-phosphate) do not exert the inhibiting effect. It is suggested that the inhibition of phosphodiesterase from rod outer segments of retinae is caused by the interaction of 3-hydroxypyridines with the hydrophobic microenvironment of the active site of the enzyme.

[The chemical nature of the fluorescing products accumulating in the lipids of the crystalline lenses of mice with hereditary cataract]. / Khimicheskaia priroda fliuorestsiruiushchikh produktov, nakaplivaiushchikhsia v lipidakh khrustalikov myshei s nasledstvennoi kataraktoi.

The content of diene conjugates (lipid hydroperoxides) was shown to be significantly higher in lipids extracted from the lenses of mice with hereditary cataract than in the controls. The same holds true for characteristics of fluorescence of the end-product of lipid peroxidation. Two (low- and high-molecular weight) peaks were detected in chromatographic lipid profile of cataract lenses measured by fluorescence on Sephadex LH-20 column, whereas only one (high-molecular weight) peak was found in lipids from normal lenses. It was established that high-molecular weight fluorescent fractions corresponded to lipid components of lipofuscin-like pigments. NMR and mass spectrometry of low-molecular weight fractions suggested that they contained predominantly products of free radical oxidation of long chain polyunsaturated fatty acids (C22:6).

[Changes in the cyclic nucleotide level and the inhibition of human thrombocyte aggregation in 3-hydroxypyridine exposure]. / Izmenenie urovnia tsiklicheskikh nukleotidov i tormozhenie agregatsii trombotsitov cheloveka pri deistvii 3-oksipiridinov.

The effect of six 3-oxypiridine derivatives (at a concentration of 10(-3) and 5 X 10(-3) M) on cyclic nucleotide level in human platelets and platelet aggregation was studied. Five 3-oxypiridine derivatives were shown to depress platelet aggregation, four of them causing the increase in cAMP platelet level. The correlation between antiaggregation activity of 3-oxypiridine derivatives and their ability to rise cyclic nucleotide level in human platelets is discussed.

[Inhibition of platelet aggregation and cyclic nucleotide phosphodiesterase (specifically cyclAMP) by 3-hydroxypyridine derivatives]. / Tormozhenie agregatsii i ingibirovanie fosfodiésterazy tsiklicheskikh nukleotidov (spetsifichnoi dlia tsAMF) trombotsitov proizvodnymi 3-oksipiridina.

The effects of 3-hydroxypyridine (3-HP) derivatives on platelet aggregation and platelet phosphodiesterase (PDE) of cyclic nucleotides (cAMP-dependent) were studied. It was shown that some derivatives of 3-HP inhibit platelet aggregation (the most pronounced effect was exerted by 2-benzyl-3- oxypyridine ). Several derivatives o 3-HP given in a concentration 10(-3) M were discovered to inhibit PDE by 40 to 75%. No correlation was found between the efficacy of 3-HP as antiaggregation agents and PDE inhibitors.