Purpose: To replicate the finding of the association of five CDKN2B-AS1 gene polymorphisms (rs7865618, rs1063192, rs944800, rs2157719, and rs4977756) with primary open-angle glaucoma (POAG) and to analyze them for possible association with pseudoexfoliation glaucoma (PXFG) in a Caucasian population of Central Russia. Methods: A total of 932 participants of Russian ethnicity (self-reported), including 328 patients with PXFG, 208 patients with POAG (high-tension glaucoma), and 396 controls, were enrolled in the study. The SNPs were analyzed for possible associations using logistic regression. Results: Several haplotypes based on the studied SNPs were associated with POAG (three haplotypes) and PXFG (six haplotypes). Haplotype AAAGG of loci rs1063192-rs7865618-rs2157719-rs944800-rs4977756 conferred the highest risk for both POAG (OR = 3.99, р perm = 0.001) and PXFG (OR = 2.84, р perm = 0.001). Conclusions:The CDKN2B-AS1 gene was associated with an increased risk of both POAG and PXFG in Caucasians of Central Russia. The gene may be related to the development of various types of glaucoma.

A number of novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole derivatives 2 were obtained by alkylation mainly in the 1H-tautomeric form of 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole or its 8,9-dimethyl-substituted analog 4-chlorobenzyl bromide, 4-chloroacetic acid fluoroanilide, and 4-tert-butylphenacyl bromide in neutral medium. Compounds 3 were cyclized and synthesized earlier with 11-phenacyl-substituted diazepino[1,2-a]benzimidazoles upon heating in conc. HBr. The chemical structures of the compounds were clarified by using the 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR) technique. Anxiolytic properties were evaluated using the elevated plus maze (EPM) and open field (OF) tests. The analgesic effect of compounds was estimated with the tail flick (TF) and hot plate (HP) methods. Besides, possible the influence of the test compounds on motor activities of the animals was examined by the Grid, Wire, and Rotarod tests. Compounds 2d and 3b were the most active due to their prominent analgesic and anxiolytic potentials, respectively. The results of the performed in silico analysis showed that the high anxiolytic activity of compound 3b is explained by the combination of a pronounced interaction mainly with the benzodiazepine site of the GABAA receptor with a prominent interaction with both the specific and allosteric sites of the 5-HT2A receptor.

Introduction: The purpose was to study the pharmacokinetic properties of RU-1205 with the previously identified kappa-agonistic and analgesic effects after parenteral administration. Materials and methods: Pharmacokinetic parameters of RU-1205 after intravenous and subcutaneous administration at doses of 10 mg/kg and 50 mg/kg, respectively, were investigated, using the method of high-performance liquid chromatography with measurement of the compound according to a pre-established calibration curve. The indices of the area under the pharmacokinetic curve, clearance, half-life, residence time of the drug molecule in the body, total (apparent) volume of distribution, as well as the indicator of absolute bioavailability for subcutaneous administration were calculated. Tissue distribution and excretion of RU-1205 were also studied. Evaluation of metabolism of RU-1205 was conducted in silico, using the PALLAS 3.00 software, with the use of specific tests with CYP 450 substrates and by studying the ability of RU-1205 to form conjugates with endogenous acids. Results and discussion: It was found that after a single intravenous administration, the investigated substance was determined in the blood for 12 h; the half-life was 8.49 hours. The absolute bioavailability after subcutaneous administration is 57.35%. RU-1205 is eliminated within 3–4 days. The main route of excretion is extrarenal. The biotransformation of the substance probably proceeds mainly with the formation of oxidized forms of the initial molecule according to the reactions of the first phase of metabolic transformation, so the chance to observe phase 2 of the metabolism could be very low. Conclusion: The test substance undergoes a long process of elimination, has the highest tropism to the elimination organs and undergoes active biotransformation processes in the body of animals.

Оригинальная статья Original article Елисеева НВ. Репликативное исследование ассоциаций полиморфных локусов генов … Eliseeva NV. A replicative study of the associations of polymorphic loci … 199 кусы гена LOXL1 -rs893818 и rs4886776 ассоциированы с развитием первичной открытоугольной глаукомы у мужчин Центрального Черноземья РФ. Ключевые слова: первичная открытоугольная глаукома; ассоциации; LOXL1; полиморфизм Для цитирования: Елисеева НВ. Репликативное исследование ассоциаций полиморфных локусов генов LOXL1 и CDKN2B-AS1с развитием первичной открытоугольной глаукомы у мужчин Центрального Черноземья РФ. Научные результаты биомедицинских исследований.

РЕЗЮМЕВ обзоре литературы освещаются этапы развития полногеномных ассоциативных исследований (GWAS) первичной открытоугольной глаукомы (ПОУГ). В настоящее время эта проблема является развивающейся и одной из самых сложных в офтальмологии. Рассмотрены основные GWAS ПОУГ и установленные GWAS-значимые полиморфизмы, ассоциированные с ПОУГ. Освещение темы GWAS ПОУГ будет интересно для офтальмологов, а материалы о GWAS-значимых локусах могут быть использованы как при отборе полиморфизмов при репликативных исследованиях ПОУГ в различных популяциях России, так и для расширения представлений о молекулярно-генетических механизмах развития заболевания.