[The antiallergic eye drops "polynadyme": development, experimental and clinical studies].

The antiallergic eye drops "Polynadyme", proposed by the Helmgolz Moscow Research Institute of Eye Diseases, have been prepared by the "Sintez" PJSC (Kurgan). The drops exert a combination of antihistaminic and vasoconstrictive effects and, for better tolerability, contain a low-toxic preserving complex. The drops are polymer-based, which ensures a long action and an artificial tear effect. Preclinical rabbit trials have shown the safety of the "Polynadyme" eye drops, their specific activity in preventing an allergic reaction, and their antiallergic effect on a model of allergic conjunctivitis. Comparative clinical trials covering 150 patients have yielded excellent and good results in 93% of cases. In acute allergic reactions, hyperemia, itch, and burning diminished just 5 minutes after administration. The "Polynadyme" eye drops are effective in treating pollinous conjunctivitis, spring (vernal) keratoconjunctivitis, allergic reactions when wearing contact lenses, the dry eye syndrome, drug-induced and toxicoallergic conjunctivitis, and other ocular allergic reactions.

[Sodium sulfapyridazine in new delayed-action bases for the treatment of bacterial conjunctivitis]. / Sul'fapiridazin-natrii v novykh prolongiruiushchikh osnovakh dlia lecheniia bakterial'nykh kon''iunktivitov.

Possible preparation of 10 per cent sodium sulfapyridazine ophthalmic drops containing aubazidan, a microbial polysaccharide, providing prolongation of the drops action and stability on the storage was studied. The pharmacokinetic studies showed that aubazidan which is a natural polymer provided high prolongation of the sulfapyridazine effect in the tissues of the anterior part of the eye in rabbits. The prolonged effect was similar to the previously observed effect of the solutions containing synthetic polymers such as 1 per cent polyacrylamide and polyvinyl . Satisfactory tolerance by the rabbit eye tissues of 6-fold daily instillations of the 10 per cent sodium sulfapyridazine solution with aubazidan for the observation period of 1 month was stated. When stored in vials the 10 per cent sodium sulfapyridazine ophthalmic drops with 0.5 per cent of aubazidan preserved the stability for 24 months with respect to the colour, transparency, viscosity, pH and drug content. It was demonstrated with using the agar diffusion method and Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Pseudomonas aeruginosa as the test cultures that sodium sulfapyridazine completely preserved its antimicrobial activity in the presence of aubazidan. The data suggested that clinical trials of the 10 per cent sodium sulfapyridazine solution with 0.2-0.5 per cent of aubazidan were promising in prevention and therapy of bacterial conjunctivitis.

[Delayed hypersensitivity to the antigens of the herpes simplex virus and herpetic resistance induced in mice by the administration of xenogeneic lymphocytic ultrafiltrates]. / Giperchuvstvitel'nost' zamedlennogo tipa k antigenam virusa prostogo gerpesa i protivogerpeticheskaia rezistentnost', indutsirovannye u myshei vvedeniem ksenogennykh limfotsitarnykh ul'trafil'tratov.

Experiments on mice have shown that ultrafiltrates, prepared from lymphocytes obtained from the spleen of horses immunized with herpes vaccine and from human tonsils, contain herpes-specific transfer factor inducing delayed hypersensitivity. The antiherpetic resistance of mice has been found to achieve its maximum if herpes simplex antigens are introduced after the injection of the preparation of transfer factor.

[Computer bank of amino-acid sequences of protein hormones. Analysis of evolutionary, conformational and physico-chemical properties of the individual sites of sequences in superfamilies of proinsulin and proglucagon]. / Komp'iuternyi bank aminokislotnykh posledovatel'nostei belkovykh gormonov. Analiz évoliutsionnykh, konformatsionnykh i fiziko- khimicheskikh svoistv otdel'nykh uchastkov posledovatel'nostei v supersemeistvakh proinsulina i progliukagona.

The correspondence schemes for the amino acid sequence families from different animal species for two superfamilies of protein-peptide hormones and their precursors, i.e., proinsulin-IGF-prorelaxin and proglucagon-pro (PHM-VIP)-prosomatocrinin, were constructed. These schemes were used for the local intra- and interfamilial comparison of the sequences; the average profiles of hypothetical secondary structure of individual sites of these sequences according to Chow and Fasman were obtained, and the profiles of their physico-chemical properties (e. g., hydrophobicity and volume of side amino acid radicals) were computed. An analysis of the profiles obtained demonstrated that despite the apparent similarity of the tertiary structure of IGF and relaxin, on the one hand, and of insulin, on the other, the latter is devoid of the insulin-like receptor (effector) site, whereas in the case of IGF, this site is modified by additional links of the peptide chain. Based on the reciprocal comparison of prosomatocrinin with proglucagon and pro (PHM-VIP), it was assumed that the C-terminal fragment of prosomatocrinin separated from somatocrinin by a single arginine residue is a second glucagon-like peptide in the precursor molecule, which apparently possesses a biological activity.

[Computer bank of amino acid sequences of protein hormones. Comparative analysis of the sequences in pro-opio-melanocortin, proenkephalin and prodynorphin: detection of phorphin--the 4th repeating peptide in prodynorphin]. / Komp'iuternyi bank aminokislotnykh posledovatel'nostei belkovykh gormonov. Sravnitel'nyi analiz posledovatel'nostei v gruppe proopiomelanokortina, proénkefalina i prodinorfina: obnaruzhenie forfina--chetvertogo povtoriaiushchegosia peptida v prodinorfine.

Using a BESM-6 computer, a computer system for accumulation and comparative analysis of amino acid sequences (AS) of protein-peptide hormones and their precursors (the so-called computer bank of protein hormone AS) was developed. A Fortran-based program designed for construction of correspondence schemes of AS and their local similarity profiles was elaborated. In combination with the previous programs this system allows a rapid inclusion of the newly deciphered sequences into the corresponding homologous groups, thus complementing the correspondence scheme and specifying the evolution profiles. A comparative analysis of AS in proopiomelanocortin (POMC), proenkephalin (PENK) and prodynorphin (PDIN) revealed evolutionary-conservative and variable sites. The conservative sites of AS are active centers of the hormones. The leu-enkephalin analog, phorphin, the fourth repeating peptide of this precursor, was detected in prodynorphin, which, similar to beta-neo-endorphin, dynorphin and rimorphin may possess a biological activity. The similarity of the effector sites of the melanotropin sequence from POMC to the met-enkephalin sequence from PENK and leu-enkephalin sequence from PDIN as well as to gastrin and cholecystokinin was established. This may suggest that the hormone-receptor complexes in target organs of these hormones are also similar.

[Structural-functional organization of protein hormone molecules]. / Nekotorye aspekty strukturno-funktsional'noi organizatsii molekul belkovykh gormonov.

Our experimental results and literature data based on present-day concepts of molecular evolution of proteins have formed the basis for a hypothesis on the structural-functional organization of protein hormone molecules. This hypothesis postulates the existence of three types of the peptide chain sites, which play different roles in the biological action of hormones, i.e. effector (active), acceptor (binding) and accessory ones. The local similarity spectra have been computed and used for a comparison of the amino acid sequences of related hormones belonging to different groups. The positions of maxima, slopes and minima in these spectra of the molecules of peptide and some protein hormones are correlated with a most probable localization of the effector, acceptor and accessory sites, respectively.

[Nomographic representation of McLachlan's statistics for the analysis of local similarity between amino acid sequence]. / Normograficheskoe predstavlenie statistiki Maklaklana dlia analiza lokal'nogo skhodstva aminokislotnykh posledovatel'nostei.

Using McLachlan's method of probability calculation and amino acid compositions of 108 protein families, the changeability of probability distribution of local similarity of amino acid sequences on the composition of the sequences has been investigated. Probability distributions were shown to have high degrees of constancy and nearly coincide with the distribution corresponding to the composition averaged upon all families. Using this average composition, cumulative probability distributions corresponding to sequence regions compared (of 3, 4, ..., 50 residues long) have been calculated and draws for "unitary", "genetic", "physico-chemical" and "evolutionary" matrices of amino acid similarity. These statistical nomogramms may be employed for quick non-computer evaluation of the significance of local amino acid similarity.

[Construction of optimal alignment of two amino acid sequences: a solution of the problem of unnecessary gaps]. / Ustanovlenie optimal'noi skhemy sootvetstviia dvukh aminokislothykh posledovatel'nostei: reshenie problemy lishnikh probelov.

A computing method for calculation of total similarity of two amino acid sequences depending on the number of gaps introduced into these sequences has been developed. It was based on Needleman--Wunsch--Sankoff's principles. The application of the method to randomized sequences enables us to select the optimal alignment of real sequences, in which the number of gaps is statistically justified. In this paper an example of the application of this approach is described and the statistically optimal alignment of somatotropin and prolactin amino acid sequences with two gaps is suggested.

[An analysis of local similarities in the primary structures of protein hormones]. / Analiz lokal'nogo skhodstva pervichnykh struktur belkovykh gormonov

An analysis of primary structures for local similarities has been performed for a number of protein hormones. The statistical MacLachlan's technique and three matrices of amino acids similarities: in respect to the genetic code (M1), physico-chemical properties (M2), interchangeability of amino acids in homologous proteins (M3) have been used. When comparing prolactin and growth hormones, four zones of high structural similarity have been found. Comparison of beta-subunits of interstitial-cell and thyroid-stimulating hormones has shown two zones of high similarity. Using M3 matrice, non-homogeneity of the self local similarity of structure has been shown for prolactin, growth hormone, beta-lipotropin, proinsulin and parathormone. For the latter three hormones, the high evolutionary conservative regions coincide with the active sites of structure. It is suggested that such regions in the structures of prolactin and growth hormone also provide the active function.