Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration

BACKGROUND: OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance. AIMS: To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502. MATERIAL AND METHODS: The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg. RESULTS: The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled. CONCLUSION: OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance

Environmental monitoring of fish in the Paz watercourse

Appendix 7/15 of the publication "State of the environment in the Norwegian, Finnish and Russian border area 2007" (The Finnish Environment 6/2007)

State of fish populations in small forest lakes in the Norwegian, Finnish and Russian area

Appendix 9/15 of the publication "State of the environment in the Norwegian, Finnish and Russian border area 2007" (The Finnish Environment 6/2007)

Structure- and interaction-based design of anti-SARS-CoV-2 aptamers

Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity by using small-angle X-ray scattering, cytometry, and fluorescence polarization. By using a new iterative design procedure, structure- and interaction-based drug design (SIBDD), a highly specific aptamer to the receptorbinding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variant

Вакцинопрофилактика пневмококковой инфекции у детей

Pneumococcal infection remains one of the leading reasons for infant mortality from vaccine-preventable infections. Today vaccination is the most effective way to prevent diseases caused by antibiotic-resistant pneumococci. In the article, authors present current approaches to vaccinal prevention of pneumococcal diseases. The plan of action for carrying out active immunoprophylaxis of pneumococcal infection is explained in detail for both healthy children and patients from risk groups for severe pneumococcal diseases development. The published work is based on key points of the guidelines of the Ministry of Health of the Russian Federation on vaccinal prevention of pneumococcal infection (developed and approved by the professional association of pediatricians «The Union of Pediatricians of Russia»).Пневмококковая инфекция остается одной из ведущих причин детской смертности от вакциноуправляемых инфекций. Вакцинация на сегодняшний день является наиболее эффективным направлением профилактики заболеваний, вызываемых устойчивыми к антибактериальным препаратам пневмококкам. В статье коллективом авторов представлены актуальные подходы к вакцинопрофилактике болезней пневмококковой этиологии. Подробно разъяснен алгоритм действий при проведении активной иммунопрофилактики пневмококковой инфекции как здоровых детей, так и пациентов из групп риска по развитию тяжелых форм пневмококковых заболеваний. Публикация основана на ключевых позициях методических рекомендаций Министерства здравоохранения РФ по вакцинопрофилактике пневмококковой инфекции (разработанных и утвержденных профессиональной ассоциацией детских врачей «Союз педиатров России»).КОНФЛИКТ ИНТЕРЕСОВАвторы статьи подтвердили отсутствие конфликта интересов, о котором необходимо сообщить

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Clinical and microbiological evaluation of the efficacy of autoprobiotics in the combination treatment of chronic generalized periodontitis

Combination treatment of patients with inflammatory periodontal diseases may be ineffective due to the variability of periodontal pathogens and the polyetiology of the disease. This disadvantage can be overcome by using highly antagonistic, enzymatic, and immunostimulating drugs, in addition to the main treatment. The objective of this study is to evaluate the efficacy of autoprobiotics clinically and microbiologically in the combination treatment of chronic generalized periodontitis. The presented study involved a survey of 37 patients aged 29 to 64 years with mild chronic generalized periodontitis. The patients were divided into three groups. Group I consisted of patients whose combination treatment included an S. salivarius-based autoprobiotic (subgroup 1 - patients who had their periodontal pockets irrigated with an autoprobiotic, subgroup 2 - patients who used oral baths with autoprobiotic). Group II consisted of patients who used a common S. salivarius-based probiotic in combination treatment (subgroup 1 - patients who had their periodontal pockets irrigated with a probiotic, subgroup 2 - patients who used oral baths with a probiotic). The control group consisted of patients with mild chronic generalized periodontitis, whose combination treatment consisted of professional oral hygiene and correction of individual hygiene. Microbiological examination of the content of periodontal pockets was carried out using PCR screening for periodontal pathogens, such as P. gingivalis, T. denticola, T. forsythia, P. intermedia. Based on the clinical and microbiological results of the study, the efficacy of an autoprobiotic and probiotic based on S. salivarius in the combination treatment of mild chronic generalized periodontitis was demonstrated

Structural and electrical properties of Mg–Cu- and Mg–Cu–Li-doped bismuth niobate semiconductors with the pyrochlore structure

This work studies a series of synthesized Bi$_{1.6}$Mg$_{0.8-x}$Cu$_x$Nb$_{1.6}$O$_{7-\delta}$ ($x$ = 0.2, 0.4) semiconductors and their Lidoped compositions. A detailed structure investigation combining high-resolution neutron-, synchrotron-, and X-ray diffraction methods, as well as DFT calculations, revealed the preferential location of Cu and Li atoms at the Bi sites and Mg atoms at the Nb ones. According to high-temperature X-ray diffraction data, a structural modification caused by the activation of oxygen transport occurs at 200°C. The linear thermal expansion coefficient was found to be 3.6–4.6⋅10$^{−6}$ K$^{−1}$ (50–400°C). Magnetic susceptibility measurements allowed us to determine weak antiferromagnetic exchange interactions. The direct band gap was predicted using the DFTHSE03 hybrid functional calculation, and the optical direct band gap was estimated at 2.3–2.4 eV. Impedance spectroscopy and a dc four-probe technique were also employed to examine the samples$^,$ electrical properties. The high mixed electronic-ionic conductivity of the pyrochlores was detected, while the vacancies created by Lidoping in Bi$_{1.5-y}$Li$_y$Mg$_{0,375}$Cu$_{0,375}$Nb$_{1.5}$O$_{7-\delta}$ have been found not to affect the conductivity. Besides, the pyrochlores are chemically compatible with the La$_{0.7}$Sr$_{0.3}$MnO$_3$ perovskite (up to 800°C). These make us believe that the studied Mg–Cu- and Mg–Cu–Li-doped bismuth niobate semiconductors can become the basis for composite electrodes to boost their oxygen conductivity

Effect of Li and Li-RE co-doping on structure, stability, optical and electrical properties of bismuth magnesium niobate pyrochlore

New Bi$_{1.5}$Mg$_{0.9-x}$LixNb$_{1.5}$O$_{7–δ}$ (x = 0.25; 0.40) and Bi$_{1.4}$RE$_{0.1}$Mg$_{0.5}$Li$_{0.4}$Nb$_{1.5}$O$_{7–δ}$ (RE – Eu, Ho, Yb) compounds with the pyrochlore structure were synthesized. The displacements of the A-site atoms (96g) and O' ones (32e) as well as the Li and RE atoms distribution in the A-sites were determined. The dopant distribution was proven by ab initio calculations. The most preferable (Bi$_{1.5}$Li$_{0.5}$)(Nb$_{1.5}$Mg$_{0.5}$)O$_7$ model was predicted with a direct band gap of 3.18 eV corresponding to the experimental Eg for Bi$_{1.5}$Mg$_{0.5}$Li$_{0.4}$Nb$_{1.5}$O$_{7–δ}$. The thermal stability of the compounds in air up to 1100–1220 °C and the reducing atmosphere up to 400 °C was determined. The charge disbalance in the A$_2$O' sublattice and the oxygen vacancies predetermine the dielectric behavior of the ceramics up to 200 °C, the mixed conductivity at high temperatures (T > 200 °C), and the proton transport up to 400 °C