Search

This work presents data on the relationship between the oligomeric state and catalytic activity of β-like DNA polymerases isolated from three cancer cell lines upon replacement of magnesium ions with iron. It was shown that the suppression of the catalytic activity of β-like DNA polymerases in the presence of divalent iron ions is related to enzyme oligomerization that can be responsible for the suppression of the magnetic isotope effect.

A new synthesis of N-(5-hydroxynicotinoyl)-L-glutamic acid via a 5-hydroxynicotinic acid imidazolide intermediate has been developed. Its calcium salt (Ampasse) has been synthesized and its structure was studied by X-ray diffraction analysis. The reaction conditions for all stages of the process have been optimized and a method for the purification of the substance has been improved.

The fundamental possibility of obtaining ultrashort (50n-100n) single-stranded polydeoxyribonucleotides by the method of radiation-chemical destruction of total yeast DNA was established and their anticancer activity was shown.

It is shown theoretically that the mechanism of the rapid coagulation of metal nanospheres into a nanowire in a quantum vortex proposed by E. B. Gordon et al. (Low Temp. Phys., 2010, 36, 590) could not be realized, due to the enormous heat release expelling the nanospheres from the vortex. Also, Gordon's hypothesis on nanowire formation in quantum vortices contradicts the observations that nanowires form above the λ-point (where no quantum vortices exist) and on superfluid helium's surface (parallel to it), which is always perpendicular to the quantum vortices. The nanowire formation process in bulk and dropwise liquid helium is described as a special case of aggregation controlled by diffusion in an external electric field. The nanosphere charging occurs due to the thermoelectric emission from their overheating and also laser ablation. The charged nanospheres attract neutral ones to minimize the electrostatic energy and are also attracted to elevations (field concentrators) on the conductive surfaces surrounding the experimental volume. Both processes lead to nanowire formation and drift prevails over diffusion in both cases. The described mechanism leads to the formation of self-similar anisometric structures in agreement with experimental data.

An experimental and computational study of the formation of pure iron nanoparticles, carbon nanoparticles (soot), and binary carbon-coated iron nanoparticles during the pyrolysis of iron pentacarbonyl–argon, ethylene–argon, and iron pentacarbonyl–ethylene–argon mixtures, respectively, behind reflected shock waves is carried out. The shape and size distribution of these nanoparticles are examined on a Zeiss Ultra plus ultrahigh-resolution field-emission scanning electron microscope. The binary iron–carbon particles were also investigated by high-resolution transmission electron microscopy and high-angle annular dark-field imaging (HAADF STEM) on a FEI Osiris transmission electron microscope equipped with a Bruker SuperX detector. Detailed kinetic simulations of the formation of these three types of particles are performed, which predict the concentration, average size, and size distribution of particles.

We investigated chiroptical characteristics of homochiral solutions of biomimetics. Our results experimentally substantiate the role of change in the chirality sign during spontaneous formation of supramolecular helical structures. This self-organization presents evidence of a fundamental synergistic law of change in the chirality sign during the transition to a higher hierarchical level that is valid for modular prebiotic homochiral systems and basic molecular biological systems.

Having investigated chiroptical characteristics of homochiral solutions of biomimetics the rule of changing a chirality sign in spontaneous formation of supramolecular helical structures was experimentally substantiated. This self-organization presents evidence of a fundamental synergetic law of changing the chirality sign during the transition to a higher hierarchical level, being of common for modular prebiotic homochiral systems and basic molecular biological systems.

I.I. Mechnikov's hypothesis that the key to prolongation of life lies in the introduction of useful microflora to the gut was not proved. Any microflora needs nutrition and perceives the human body only as a nutrient substrate. Destruction of the basement membranes, that delimit the contacting with aggressive microbiological environment epithelium from the deeper parts of the body, can lead to chronic inflammatory diseases and aging of the skin as a consequence of the invasion of microorganisms. At the ultrastructural level it has been shown by the example of prostatitis and skin aging changes. Coupled with the penetration of germs flow of immune cells may cause autoimmune reactions due to abrupt changes in the molecular design of the intermembrane transport. Thus, the physiological process of macroorganism aging can be viewed as a consequence of its microbiological destruction.

The safety of a new nootrope and neuroprotector--calcium N-(5-hydroxynicotinoyl)-L-glutamate (ampasse)--has been evaluated. It is shown that ampasse at a dose of 6.7 mg/kg (10 times the maximum therapeutic dose for humans) did not affect the reproductive function in experimental animals and did not produced any embryotoxic and teratogenic effects.

Human papilloma virus was detected by polymerase chain reaction in patients suffering from chronic cystitis with hyperplastic changes in urinary bladder mucosa. In most of the examinees (90%) it was HPV of highly oncogenic type 16. Panavir added to combined treatment of such patients produced a significant positive result in long-term period. Improvement was observed both in subjective assessment and the absence of dysuria episodes.

The pharmacokinetics of N-(5-oxynicotinoyl)-L-glutamate (ONG) was studied in rats (doses, 20, 100 and 500 mg/kg) and rabbits (50 mg/kg) after bolus administration of calcium salt of N-(5-oxynicotinoyl)-L-glutamic acid (Ampasse preparation). The ONG concentration in the blood serum was determined by HPLC assay with fluorimetric detection. The lower limit of accurate detection for ONG was 100 ng/ml. The ONG pharmacokinetics in rats was linear at relatively small doses (20-100 mg/kg) but nonlinear at a large dose (500 mg/kg). The ONG concentration decay had a two-phase character in both rats and rabbits, so that the pharmacokinetic profiles were fitted to a biexponential equation of the two-compartment model. Systemic pharmacokinetic parameters determined in rats and rabbits, respectively, were as follows: total clearance, 18 and 15 ml/(min kg); steady state distribution volume, 330 and 880 ml/kg; mean retention time, 0.3 and 1.0 h; half-life, 0.73 and 2.3 h. Using the allometric approach to the interspecies extrapolation of the pharmacokinetic data, the half-life of ONG in humans is predicted to be 4 h.

Significant and reliable activity of panavir was shown in experiments on mice intramuscularly infected with the rabies virus. The animal protection depended on the dose of panavir and the treatment scheme. The reliable protection (30-45% of the mice, p0.05-0.01) was observed only after the panavir intramuscular injection to the site of the virus inoculation (the infection atrium), but not after the systemic (intraperitoneal) administration. High titers of the virus-neutralizing antibodies (7.92-10.45 IU/ml), comparable to the antibody titers in the combined suspensions of the brain tissues (6.01-10.45% IU/ml), were detected in the combined sera of the survived animals treated with panavir. For the first time a quantitative method for determination of the virus-neutralizing antibody levels in IU/ml was used (the FAVN test, the gold standard for comparative evaluation of the level of the vaccinal and infective antirabies immunity).

Mitogenic properties of panavir, as well as its effect on the grippe virus reproduction in cell systems in vitro and the effect on the survival of mice with the experimental grippe infection were studied. It was shown that panavir had no cytotoxic action whereas it was characterized by pronounced mitogenic activity and subsequently could be considered as a perspective immunomodulator. Under in vitro conditions with the use of relatively high doses for the cell contamination with the grippe virus, panavir lowered the virus production in the cell systems. When the contaminating doses were low, panavir inhibited the virus production detected at the early stages of the infection. In the in vivo studies on mice with the experimental grippe infection panavir showed antigrippe activity against both the romantadine resistant and the remantadine nonresistant populations of the grippe A virus.

The topicality of the human papillomavirus infection problem is due to a worldwide increase in the incidence of its recurrent forms and associated cancer pathology. Infection relapses and their negative impact on the personal and social aspects of life necessitate a search for safe drugs that affect various elements in the pathogenesis of the infection. Material and methods. The study included 92 patients with recurrent anogenital warts. All patients underwent combined therapy, including laser destruction and administration of Panavir suppositories. Results. Application of Panavir rectal suppositories in combination with destruction of anogenital warts provided an increased remission period in 90.22% of the patients. No allergic reactions and side effects were observed. Conclusions. A high clinical efficacy and good tolerability of Panavir suppositories observed in 90.2% of patients make it possible to recommend the combined method for extensive use in the treatment of human papillomavirus infection.

Рецидивы герпетической инфекции, их отрицательное влияние на психосоциальный и психосексуальный аспекты жизни обусловливают необходимость поиска безопасных препаратов, влияющих на различные звенья патогенеза инфекционного процесса. Цель исследования — определить эффективность ректальных суппозиториев Панавир при терапии пациентов с рецидивирующей герпетической инфекцией. Материал и методы. Под наблюдением находились 60 человек с рецидивирующей герпетической инфекцией в возрасте от 22 до 45 лет, с количеством рецидивов от 3 до 5 в год и давностью заболевания от 12 мес до 5 лет. Пациенты были рандомизированы на две группы по 30 человек: в 1-й группе больные получали суппозитории Панавир для лечения рецидивов генитального герпеса, во 2-й — для терапии обострений орофасциального герпеса. Препарат назначали по 200 мг ректально на ночь, через 24 ч (10 свечей на курс). Результаты. В результате проведенной терапии было установлено, что у 9 больных 1-й группы на фоне применения суппозиториев Панавир купирование субъективных симптомов (зуд, жжение, покалывания, боли) произошло через 1—2 дня, на 3-й день — еще у 18 пациентов. Во 2-й группе пациентов с орофасциальным герпесом купирования субъективных симптомов удалось достичь у 11 человек через 2 дня, у 17 — через 3 дня лечения. Результаты анализа динамики кожных проявлений оказались сходными в обеих группах. Заключение. Применение Панавира в форме ректальных суппозиториев как препарата выбора в терапии пациентов с герпетической болезнью обеспечило сокращение длительности рецидивов у 90% исследуемых и увеличение межрецидивного периода у 86—93% больных. Ключевые слова: герпес, рецидивирующее течение, химические аналоги нуклеозидов, Панавир, безопасность, целесообразность и эффективность терапии. Relapses of herpetic infections and their negative effect on the psychosocial and psychosexual aspects of life make one to search for safe drugs that would affect different elements of infection pathogenesis. Objective. To determine the effectiveness of Panavir rectal suppositories in treatment of patients with recurrent herpes. Material and methods. The study included sixty 22—45-yearold patients with recurrent herpes; the relapse rate was 3—5 relapses per year; disease duration ranged from 12 months to 5 years. The patients were randomly divided into two groups with 30 patients per each group. The patients received Panavir suppositories to treat recurrent genital herpes (Group 1) or orofacial herpes (Group 2). 200 mg Panavir was administered rectally every night (10 suppositories per treatment course). Results. The objective symptoms (itching, burning and pin sensation, pain) were eliminated after 1—2 days in 9 group 1 patients; after 3 days, in 18 more patients. In group 2 patients with orofacial herpes, subjective symptoms were eliminated in 11 individuals after 2 days and in 17 individuals after 3 days of therapy. The results of the analysis of the dynamics of skin symptoms were similar for both groups. Conclusion. The use of Panavir rectal suppositories as a drug of choice to treat patients with herpes reduced the relapse duration in 90% of patients and increased the inter-relapse period in 86—93% of patients.