Surfaces of implanted medical devices are highly susceptible to biofilm formation. Bacteria in biofilms are embedded in a self-produced extracellular matrix that inhibits the penetration of antibiotics and significantly contributes to the mechanical stability of the colonizing community which leads to an increase in morbidity and mortality rate in clinical settings. Therefore, new antibiofilm approaches and substances are urgently needed. In this paper, we test the efficacy of a broad-range recombinant endolysin of the coliphage LysECD7 against forming and mature biofilms. We used a strong biofilm producer—Klebsiella pneumoniae Ts 141-14 clinical isolate. In vitro investigation of the antibacterial activity was performed using the standard biofilm assay in microtiter plates. We optimized the implantable diffusion chamber approach in order to reach strong biofilm formation in vivo avoiding severe consequences of the pathogen for the animals and to obtain a well-reproducible model of implant-associated infection. Endolysin LysECD7 significantly reduced the biofilm formation and was capable of degrading the preformed biofilm in vitro. The animal trials on the preformed biofilms confirmed these results. Overall, our results show that LysECD7 is a promising substance against clinically relevant biofilms.

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We studied the effect of phenotropil (25 mg/kg intraperitoneally, 5 days) on the immune and psychoemotional state of Wistar rats with LPS-induced immune stress. Hyperactivity of the immune system in animals after treatment with Pseudomonas aeruginosa LPS (100 μg/kg intraperitoneally, 3 days) manifested in a significant increase in the delayed-type hypersensitivity index, antibody titer in the reaction of passive hemagglutination, and phagocytic activity of peripheral blood neutrophils. Locomotor, orientation, and exploratory activities were reduced, while anxiety increased in animals with immune stress. Phenotropil exhibited the psychoimmunomodulatory effect under these conditions, which manifested in prevention of anxiety and fear response, increase in horizontal locomotion and exploratory behavior, and improvement of immunoreactivity.

¹ Астраханский государственный медицинский университет (АГМУ) Россия, 414000, Астраханская область, г. Астрахань, ул. Бакинская, д. 121 2 Институт молекулярной генетики Российской академии наук (ИМГ РАН) Россия, 123182, Москва, площадь академика И.В. Курчатова, д. 2 Цель исследования: изучение стресс-протекторного и иммуномодулирующего действия Семакса в условиях информационного стресса.Материалы и методы. Исследование, посвященное изучению стресс-протекторного и иммунокорригирующего действия Семакса (Met-Glu-His-Phe-Pro-Gly-Pro) в условиях экспериментального информационного стресса, выполнено на белых нелинейных крысах-самцах. Формирование стресс-реакции в условиях информационного воздействия подтверждали наличием «стрессорной триады», включающей гипертрофию надпочечников, снижение числа эозинофилов в периферической крови и наличие эрозивно-язвенного поражения слизистой оболочки желудка. Кроме этого, для оценки реактивности организма рассчитывали индекс напряженности адаптации по Л.Х. Гаркави -как показатель сбалансированности ответной реакции клеток крови на стрессогенный фактор. Функциональную активность иммунной системы лабораторных животных оценивали на основании стандартных иммунофармакологических тестов: реакции гиперчувствительности замедленного типа (РГЗТ), реакции прямой гемагглютинации (РПГА), латексного теста по изучению фагоцитарной активности нейтрофилов периферической крови, оценки изменений лейкоцитарной формулы.Результаты. Установлено, что в условиях информационного стресса изменения иммунного реагирования имеют разнонаправленный характер, что подтверждает теорию «иммунного дисбаланса» при действии стрессирующих факторов. В результате изучения влияния Семакса в условиях информационного стресса было установлено, что препарат проявил себя как эффективный стресс-протектор и иммунокорректор, снижая стресс-реактивные проявления, восстанавливая клеточную и гуморальную реакции иммуногенеза, а также фагоцитарную активность нейтрофилов.Заключение. Данное исследование расширяет базы научных изысканий в области иммунореагирования в условиях стресс-индуцированных состояний, с целью последующей разработки фармакологической стратегии коррекции выявленных нарушений посредством веществ нейропептидной структуры.Ключевые слова: информационный стресс; Семакс; реакция гиперчувствительности замедленного типа (РГЗТ); реакция прямой гемагглютинации (РПГА); фагоцитарный индекс (ФИ); фагоцитарное число (ФЧ).

Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

Синтезированы новые конденсированные пиримидиновые соединения, имеющие бензаннелированную хиназолиновую структуру с различными функциональными заместителями в положении N3 пиримидиновой системы: 2-метил-3-(2-фенил-2-оксоэтил)хиназолин-4(3H)-он; 3-(2-трет-бутил-2-оксоэтил)хиназолин-4(3H)-он; 3-[2-(1-нафтил)-2-оксоэтил]-6-бромхиназолин-4(3H)-он; 3-(2-изопропилокси-2-оксоэтил)хиназолин-4(3H)-он; 3-[2-[(4,6-диметилпиримидин-2-ил)амино]-2-оксоэтил]хиназолин-4(3H)-он. Установлено, что новые производные хиназолина оказывают корригирующее влияние на процессы пролиферации в иммунокомпетентных органах, восстанавливая количество спленоцитов и тимоцитов на фоне циклофосфановой иммунодепрессии у мышей линии СВА обоего пола 3 – 4-месячного возраста.

— In this study we have investigated the effects of melanocortins (group analogs of neuropeptides) on the psychoemotional state of rats under conditions of experimental social stress. The study was carried out on male rats which were injected intraperitoneally for 20 days with the neuropeptide drugs Semax and ACTH(6-9)-ProGly-Pro at a dose of 100 μg/kg/day starting from the 1st day of stress exposure. The psychoemotional state of the animals was evaluated by means of the behavioral test of elevated cruciform maze. It was found that intraperitoneal administration of neuropeptides (Semax, ACTH(6-9)- Pro-Gly-Pro) helps to reduce high anxiety levels in animals both with aggressive and submissive types of behavior under conditions of experimental social stress via their psychomodulatory effects.

The review deals with modern ideas of neuroimmunoendocrine regulation of physiological and pathophysiological processes in skin. The present data are provided which indicate to composite mechanisms of intercellular interactions in complex regulating systems (nervous, immune, endocrine) acting at the level of skin in normal conditions, as well during the posttraumatic period. We describe different modes for participation of endocrine and nervous systems in immunologically induced skin inflammation. The data are provided confirming localization of adrenergic receptors on membranes of immunocompetent cells and leukocytes, on regulatory effects of hypothalamus upon immune functions, about multidirectional actions upon inflammation of sympathetic and parasympathetic nervous system etc.There are sufficient data on promotion of pathophysiological changes and reconstitution processes in the skin due to effects of local immune cells and bioactive substances expressed by them. The course of skin wound regeneration depend on the type of damage, degree and a phase of healing process. Posttraumatic reparative potential of skin is often limited by the infectious processes initiated by local microflora, products of cell disintegration and necrotic tissues. The cause-effect relationship is proven by arising inflammation which is implemented by inclusion of immune protection responses. The increased necrotic area and suppuration of the wound occurs die to inhibition of system of the phagocytizing macrophages. However, activation of this system brings about formation of the connective tissue capsule around the inflammation focus within early terms.We also discuss the issues of reparative skin regeneration which of great medico-social value, in connection with considerable prevalence of traumatic events and their social consequences, followed by expressed cosmetic defects. Evolving neurocognitive problems lead to decreased quality of the patient’s life, development of social disadaptation and further deprivation. The role of nervous system and psychological frustration in genesis of skin manifestations requires future development of the modern scientific direction, i.e., psychodermatology.Understanding of molecular mechanisms regulating the neuroimmunocutaneous interactions offers new prospectives in treatment of some skin diseases, as well as activation of the damaged skin recovery. According to the data presented in the review article, one may conclude on relevance of further studies on reparative potential of skin under interactions of homeostatic regulatory systems.