[Stimulation of proliferation by carnosine: cellular and transcriptome approaches].

Concentration of endogenous dipeptide carnosine in human muscle tissue reaches tens of millimoles. For more than 100 years of research, a lot of data concerning carnosine functions were accumulated, among which anti-aging effects are regarded most important. Heire, effect of carnosine in cell cultures was studied. It has been found that apart from the known action--an increase of the Hayflick limit and morphological rejuvenation--carnosine stimulates cell division in colony-forming assays and in the course of transition of cells to the quiescent state. The analysis of the transcriptome showed that carnosine-induced changes are mainly related to positive regulation of the cell cycle at all levels, from the onset of the DNA synthesis to chromosome condensation. One can suppose that the revealed stimulation of the cell cycle account for the carnosine-induced rejuvenation processes and a high concentration ofcarnosine in muscle tissue is required for the muscle recovery (regeneration) after excess loads.

[Experimental morphological study of posttraumatic proliferative vitreoretinopathy prevention by cell adhesion peptide Arg-Gly-Asp-Ser]. / Peptid kletochoí adgezii (Arg-Gly-Asp-Ser) v profilaktike posttravmaticheskoí proliferativnoí vitreoretinopatii (éksperimental'no-morfologicheskoe issledovanie).

Proliferative vitreoretinopathy (PVR) was induced in 25 rabbits by injection of autologous adenosine phosphate-activated platelets in the vitreous. Injury to the internal interface retinal membrane as a result of adhesion of aggregated platelets to it, followed by the formation of an epiretinal membrane, underlies the morphogenesis of experimental PVR. Proliferative processes in the retina were paralleled by destructive atrophic changes in it, which might be due to active physiological substances released in the course of aggregation. The development of PVR was inhibited by a synthetic peptide of cell adhesion with Arg-Gly-Asp-Ser amino acid sequence, which was injected simultaneously with autologous activated platelets. Possible receptor mechanisms underlying the phenomenon of inhibition of the proliferative process in the retina of experimental animals are discussed.

[Potentiation by promethazine of hypotensive effects of adrenergic drugs on intraocular pressure]. / Usilenie prometazinom gipotenzivnogo deistviia adrenergicheskikh sredstv na vnutriglaznoe davlenie.

Experiments including previous installations of promethazine (pipolphen) into the conjunctival sac followed by the topical administration of beta-adrenergic blocker timolol or a sympathomimetic drug isoptoepinal (adrenaline) have been performed on 24 rabbits (48 eyes). The substantial changes in the action mode of the mentioned drugs as the enhancement of their hypotensive effect on the intraocular pressure (IOP) have been demonstrated under the performance of the above mentioned procedure. When applied after promethazine instillations, timolol induced significantly increased outflow facility of the aqueous humor that was not usually noted in the cases of timolol topical instillations without a pretreatment of the eye with promethazine. The similar increased hypotensive effect on the IOP was noted for adrenaline when it has been used after promethazine treatment. The possible mechanisms underlying the changes in pharmacological activities of the investigated adrenergic drugs are discussed.

[Diffusion properties of water in the human crystalline lens during cataract development]. / Diffuzionnye svoistva vody v khrustalike cheloveka pri razvitii katarakty.

Normal and cataractal decapsulated lenses of man were studied by NMR method-spin echo to obtain information concerning efficient coefficients of self diffusion, times of spin-spin relaxation of water protons (T2) and water content in the lens (c) at 25 degrees C in the course of cataractogenesis. It has been found that the values T2 and c at 25 degrees C are much higher in the nuclei of completely turbid lenses than in the transparent ones; the self-diffusion coefficients in the turbid lenses were also higher. At -9 degrees C a significant decrease of the content of undestroyed by frost (bound) water was observed at the stage of mature cataract as compared to transparent lenses. It is suggested that the most specific differences between the nuclei of transparent and completely turbid lenses are related to increased diffusion mobility of water molecules, apparently, at the expense of damaged plasmic membranes of the lens fibres noted during cataract development.

[Oligomerization of water soluble proteins of rabbit crystalline lens under the action of diamide]. / Oligomerizatsiia vodorastvorimykh belkov khrustalika krolika pod deistviem diamida.

The study has examined the effects of the SH-oxidizing agent diamide (Diazane dicarboxylic acid bis-(N,N-dimethyl-amide)) on the water-soluble portion of proteins from rabbit lenses. The dialyzed protein extracts were incubated for 1-1.5 hrs with various concentrations of diamide. Treatments were monitored for alterations in sulphydryl contents, gel filtration and gel electrophoresis profiles of proteins. The response to 2 mM diamide treatment for 1 hr consists of rapid oxidation (up to 40%) of protein-bound sulphydryl groups accompanied by an appearance of polypeptides with apparent molecular weights. The protein with molecular weight of 29 kilodaltons was shown to be involved in cross-linking. The linkages in the dialyzed water-soluble lens polypeptide fraction induced by diamide may be reduced by GSH (10 mM) treatment of protein extract. The main target of oxidative insult induced by diamide in the water-soluble proteins of the lens is probably the superficially localized sulphydryl groups of crystallins. Our observations suggest that the described oxidative system of proteins may be a useful tool for cataract research.

[Results of combined use of taufon and timolol in the treatment of patients with open-angle glaucoma]. / Rezul'taty sochetannogo primeneniia taufona i timolola pri lechenii bol'nykh otkrytougol'noi glaukomoi.

The effect of taufon and timolol maleate combination on intraocular pressure and ocular hemodynamics was studied in 44 patients (63 eyes) with primary open-angle glaucoma. Combined administration of these agents elevated almost twofold the fluid discharge efficacy coefficient and normalized Becker's coefficient in 68.6 percent of patients. The patients were followed up for 8 weeks. Taufon addition to timolol modified the action of this latter drug, normalizing the ocular hemodynamics.

[Photo damage to the eye in exposure to the radiation from a Nd:YAG Q-switching laser: the physicochemical structural changes to the crystalline lens and the vitreous body]. / Fotopovrezhdenie glaza pri vozdeistvii izlucheniia Nd:YAG lazera s modulirovannoi dobrotnost'iu: fiziko-khimicheskie strukturnye izmeneniia khrustalika i steklovidnogo tela.

Structural changes in the lens and vitreous body exposed to short-pulse Nd:YAG Q-switching laser were under study. The laser was focussed in the lens nucleus or vitreous center plane. A pulse energy was 7.1-9.3 mJ, with a total of 75-100 pulses. Cataract development was induced via the formation of cavities with the guidance spot focal plane localized in the lens nucleus plane. When the focus was in the vitreous body and the laser operated in a similar energy mode, great numbers of small cavities rapidly formed, this evidencing a shock wave propagation. Specific and structural conformational changes in the lens and vitreous protein molecules were detected by nitrate quenching of the triptophane amino acid residue fluorescence. Laser exposure was found to reduce triptophanile availability for nitrates, this evidencing protein complexes aggregation (collapse); besides, laser exposure essentially increased the amino acid residue quenching constants, which fact pointed to a decreased density of the vitreous collagen and lens crystalline negative charges (increased hydratation). These findings permit a conclusion that the shifts connected with injury to the vitreous body, with macular edema, or with detachment of the retina after exposure to Nd:YAG laser may be due to collapse of the vitreous gel liquified components.

[Extracellular glycoproteins of the ocular trabecular zone in patients with primary open-angle glaucoma]. / Ekstrakletochnye glikoproteiny trabekuliarnoi zony glaz bol'nykh pervichnoi otkrytougol'noi glaukomoi.

The content of fibronectin, an extracellular glycoprotein, in the drainage out-flow system of human eyes was measured by the indirect immunoperoxidase staining technique. The degree of fibronectin accumulation in ocular tissues was evaluated by quantitative morphometric analysis. Fibronectin level in the ocular drainage system of humans grows with ageing and rapidly increases at different stages of primary open-angle glaucoma development. Increased deposit of fibronectin in trabecular tissue, mainly in the inner wall of Schlemm's canal and juxtacanalicular or cribriform part of trabecular meshwork, was demonstrated. A hypothesis explaining the development of the glaucomatous process by an adhesive impairment is proposed.

[Oxidation of pyridine nucleotides in injuries of the cornea]. / Okislenie piridinovykh nukleotidov pri povrezhdenii rogovitsy.

NADH fluorescence may serve a convenient test indicating the tissue redox status. Rabbit cornea has been incubated at ambient temperature in media of different compositions with 5.10(-5) M NADH at pH 7.0-7.3. Oxidation of NADH in the humor-substituting medium for corneal tissue incubation has been monitored by fluorescent analysis (stimulation maximum at a wavelength of 360 nm, emission maximum 460 nm). Characteristic kinetics of changes in the pyridine nucleotide fluorescence consists in its maximum intensity occurring in 10 min of the tissue incubation, followed by the fluorescence intensity reduction by the 20-30th min of the corneal tissue incubation. These changes are explained by a release of substrates, characterized by NADH oxidizing activity, from the corneal tissue, this resulting from injury to the corneal cells with humor-substituting solutions. Carnosine (10 mM) and taurine (0.05% solutions) have been found to protect the corneal tissue from injuries, in contrast to common salines.

[Morphometric analysis of lens opacification]. / Morfometricheskii analiz pomutneniia khrustalika.

A method of classifying cataractous changes in excised human cataracts that was based on separate and independent photographic documentation with subsequent quantitative evaluation of lens opacification has been proposed. The degree of lens clouding was evaluated quantitatively by measuring the optical density index and the area of clouding with certain optical density parameters (equidensities) by use of a texture analyzer system apparatus. This technique made it possible to obtain the contrast image of the lens clouding areas in the frontal projection and to determine their share in the total area of the lens surface. The precise topography of the opacities was established. The data obtained for different clinical types of cataracts help the scientist in his effort to measure clinically or scientifically significant quantitative associations between laboratory measures and cataractous changes.

[Molecular organization of protein-lipid components of the crystalline lens]. / Molekuliarnaia organizatsiia belkovo-lipidnykh komponentov khrustalika glaza.

Lens transparency is primarily a physical phenomenon and is a manifestation of the lens structural organization. Traditionally the lens is considered as a "sac filled with proteins uniformly". Such studies have described overall average properties of the lens but have dealt with neither structural nor functional inhomogeneities in the lens tissue. All morphological, biochemical and physiological processes of the lens are aimed at the maintenance of transparency and refractive index. Minimizing of the lens light scatter is created in the lens by the processes that organize regularity at two structural levels: the fiber cytoplasmic matrix (cytoskeleton and soluble protein) and the fiber cell plasma membrane. Biochemical fractions of the lens are considered that are responsible for the physical basis of lens transparency.

[Spectral characteristics of intraocular lenses and injury to the retina caused by visible light]. / Spektal'nye kharakteristiki intraokuliarnykh linz i povrezhdenie setchatki vidimym svetom.

It has been shown that intraocular lenses (IOL) prepared from polymethylmethacrylate and silicon let pass the light of short-wave visible and long-wave spectrum regions. Unlike natural lens, IOL have no yellowish coloration, which results in the appearance of chromatic aberrations and brightness of IOL during implantation. Mechanisms of damaging effects of visible light on the retina were studied. It has been shown that a week after the rat eyes were illuminated the waves "a" and "b" ERG were inhibited. At the ultrastructural level damage of the cells of the retinal pigment epithelium and of the retinal layers formed by photoreceptor cells took place. Dynamics of the damage of tissue structures of the retina by visible light was investigated. It is suggested that application of colored lenses and prophylaxis by the inhibitors of free radical oxidation will protect the retina from photochemical damage.

[Effect of carnosine on intraocular pressure]. / Vliianie karnozina na vnutriglaznoe davlenie]

It has been demonstrated in experiments on non-anesthetized rabbits that conjunctival injection of carnosine (beta-alanyl 1-histidine) caused a decrease in normal intraocular pressure and reduced prostaglandin-induced ocular hypertension. The rapid onset of the pressure response and the absence of papillary dilation in rabbits treated with carnosine were observed. It is concluded that L-carnosine can be used as a potent drug for the prevention of reactive hypertension syndrome.

The antioxidative properties of carnosine, a natural histidine containing dipeptide.

The experimental results suggest that the antioxidative function of carnosine is one of the most important manifestations of its biological role. The ability of carnosine to interact directly with lipid peroxidation products was demonstrated. The effects of carnosine on partial restoration of lens transparency in dog eyes with senile cataract which is known to be caused by lipid peroxidation were demonstrated "in vitro" and "in vivo".

[Mechanisms of retinal damage in chloroquine retinopathy]. / Mekhanizmy povrezhdeniia setchatki pri khlorokhinovoi retinopatii.

The paper presents the results of comparative electron microscopic, electrophysiological and biochemical studies of chloroquine effect on lipid peroxidation (LPO) both in vitro and in vivo (rabbits and rats). It has been shown that the progress of chloroquine retinopathy was not accompanied by the increment of the initial LPO level, and the use of ionol antioxidant did not protect the retina from the adverse effect of chloroquine. Besides, chloroquine was shown to suppress LPO in vitro. The results obtained substantiate the idea that LPO is not the primary mechanism in chloroquine retinopathy.

[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).