Presented is a review of the literature on the problem of hypoxic-ischemic perinatal brain damage in the context of alterations of astroglial regulation of neuronal energy metabolism and mechanisms of excitotoxicity. Characteristics of energy metabolism in the developing brain responsible for specificity of its damage in perinatal period, as well as cell and molecular mechanisms of disturbances of neuron-astrocyte coupling controlling regulation of neuroplasticity are discussed.

Представленное клинико-экспериментальное исследование включало диагностику эндотелиальной дисфункции методом ультразвукового исследования диаметра плечевой артерии, а так же по содержанию клеточно-гуморальных маркеров патологии сосудистого русла у пациентов с эссенциальной и рефрактерной артериальной гипертензией. Экспериментальная часть исследования осуществлена на крысах линии SHR путем моделирования дисфункции эндотелия in vivo с помощью сунитиниба. С целью определения возможности улучшения функции эндотелия триметазидином МВ к основной терапии пациентов с артериальной гипертензией был добавлен Предуктал МВ (Сервье, Франция). Крысам SHR перорально вводился триметазидин МВ на фоне терапии противоопухолевым препаратом сунитинибом. Сунитиниб выбран для экспериментального моделирования дисфункции эндотелия в связи с его побочным эффектом повышения уровня артериального давления. Нами выявлено, что триметазидин как при эссенциальной, так и при ятрогенной артериальной гипертензии, снижает содержание маркеров дисфункции эндотелия (sPECAM-1, циркулирующие апоптотические эндотелиальные клетки, циркулирующие эндотелиальные микрочастицы). Улучшение функции эндотелия сопровождается снижением уровня артериального давления на 28 % и более по сравнению с исходным уровнем. Эффективность назначения триметазидина подтверждена УЗИ диаметра плечевой артерии пациентов с эссенциальной и рефрактерной артериальной гипертензией. Механизм влияния триметазидина на эндотелиальные клетки связан со снижением содержания внутриклеточного кальция, свободных радикалов, изменением активности МАПК, а также увеличением концентрации сосудисто-эндотелиального фактора роста в 1,7 раз и более в плазме крови. Миографией брыжеечной артерии крыс SHR, леченных триметазидином и сунитинибом, определено снижение дисфункции эндотелия по сравнению с группой без триметазидина. На основании полученных результатов сделан вывод, что триметазидин может рассматриваться как патогенетическая терапия эндотелиальной дисфункции при эссенциальной и ятрогенной артериальной гипертензии, вызванной сунитинибом.

Agonists of glutamate ionotropic (NMDA) and metabotropic receptors (mGluRI and mGluRIII) had the regulatory effect on ADP-ribosyl cyclase/CD38 activity in cerebellar granular cells of newborn rats. Perinatal hypoxic-ischemic brain injury was followed by dysregulation of this mechanism.

Oxytocin is important for regulating a number of physiological processes. Disruption of the secretion, metabolism or action of oxytocin results in an impairment of reproductive function, social and sexual behaviours, and stress responses. This review discusses current views on the regulation and autoregulation of oxytocin release in the hypothalamic-neurohypophysial system, with special focus on the activity of the CD38/cADP-ribose system as a new component in this regulation. Data from our laboratories indicate that an impairment of this system results in alterations of oxytocin secretion and abnormal social behaviour, thus suggesting new clues that help in our understanding of the pathogenesis of neurodevelopmental disorders.

The aim of this work was to evaluate contribution of released membrane particles (RMP) to the development of systemic inflammatory response (SIR) after aortocoronary bypass grafting (ACBG). The number of RMP carrying surface adhesion molecules, CD62L, CD62P, CD62E, was shown to increase in the early postoperative period in parallel with the enhancement of lymphocyte plasma membrane blebbing and elevation of cytokine levels in peripheral blood. It is concluded that (1) activation of plasma membrane blebbing in peripheral blood cells underlies the appearance of RMP in circulation; (2) increased number of RMP expressing CD62L, CD62P, CD62E is a marker of intercellular communication associated with the development of SIR and suggests new mechanisms of RMP involvement in the reaction of organism to massive surgical injury.

The pathogenesis of neuronal dysfunction was evaluated from the viewpoint of cellular disturbances in NAD(+) metabolism and changes in activity of NAD(+)-utilizing enzymes (e g., ADP-ribosyl cyclase/CD38). S-100B concentration and CD38 expression on peripheral blood lymphocytes were altered in patients after surgery for coronary heart disease with extracorporeal circulation. These changes in patients during the early postoperative period correlated with variations in CD38 expression on neuronal cells from postischemic rats with cognitive dysfunction.

We have analyzed different approaches to diagnostics of autism-spectrum disorders based on identifying the genetic, morphological, neurophysiological, neurochemical, immunological, and metabolic biomarkers as well registration of specific traits revealed by scales and questionnaires. Results of application of Autism Spectrum Quotient (AQ-test) in the population of healthy adults and adults with mental disorders are discussed.

На модели перинатального гипоксически-ишемического повреждения головного мозга крыс обнаружено изменение экспрессии и активности бифункционального фермента CD38 в клетках нейрональной и глиальной природы, определяющее особенности развития реактивного глиоза и реализации функционального сопряжения между АДФ-рибозилциклазой и коннексином 43 в становлении нейрон-глиальных взаимодействий.

We studied changes in the expression and activity of a bifunctional enzyme, CD38, in neurons and glia induced by perinatal hypoxia-ischemia in rats. These changes influenced reactive gliosis and functional coupling between ADP-ribosyl cyclase and connexin 43 in the development of neuron-glia interactions.

The present views of the pathogenesis of neuronal dysfunction in critical conditions are analyzed, by taking into account of impairments of cellular NAD+ metabolism, the activity of NAD+-converting enzymes, including ADP-ribosyl cyclase/CD38, the possibilities of developing new neuroprotective strategies. Key words: neuronal dysfunction, ADP-rybosyl cyclase/CD38, NAD+, critical condition.

The currently available data on the pathogenesis of a systemic inflammatory reaction (SIR) are reviewed in terms of dys-regulation of membrane-cytoskeletal interactions, cellular adhesion, membrane particle release, and development of endothelial dysfunction as a key factor in the genesis of SIR. Key words: systemic inflammatory reaction, membrane particles, blebbing, selectines, cytokines.

Using a model of perinatal hypoxic-ischemic injury of rat brain we have found the patterns of changes in the activity of ADP ribosyl cyclase in brain cells that determine the specific features of programmed cell death and maintenance of the intracellular NAD(+) homeostasis.

На модели перинатального гипоксически-ишемического повреждения головного мозга крыс обнаружены закономерности изменения активности АДФ-рибозилциклазы клеток коры головного мозга, определяющие особенности реализации запрограммированной клеточной гибели и поддержания внутриклеточного гомеостаза НАД+.

Objective: to optimize the diagnosis of a systemic inflammatory reaction (SIR) after aortocoronary bypass surgery (ACBS) under extracorporeal circulation (EC), by examining the reaction of the peripheral blood lymphocytic plasma membrane to surgery. Subjects and methods. Eighty-three patients with coronary heart disease (CHD) who had undergone ACBS were examined. The lymphocytic plasma membrane was studied before and 1, 2, 3, and 7 days after surgery. Lymphocytes were derived on the ficoll-verografin (Pharmacia Chemical, Uppsala, Sweden) density gradient (p=1.077). The isolated cells were investigated by phase contrast microscopy (900X). Results. The patients with CHD were found to have perioperative peripheral lymphocytic plasma membrane changes (blebbing), the genesis of which was determined by impaired membrane-cytoskeleton interactions. More plasma membrane changes occurred throughout the postoperative period, with their maximum being recorded on day 1, which corresponded to the increase peak in the concentrations of interleukin-6 and tumor necrosis factor-а. Conclusion. The follow-up cell membrane changes appearing as peripheral lymphocytic blebbing reflect the development of SIR during ACBS under EC. In patients with CHD, the lymphocytic plasma membrane blebbing is of varying degrees: from early to terminal. The determination of peripheral lymphocytic blebbing allows one not only to record SIR, but also to assess its time course of changes. Key words: lymphocytic blebbing, systemic inflammatory reaction, aortocoronary bypass surgery, extracorporeal circulation.

The expression of connexin 43 and CD38 and ADP ribosyl cyclase activity in brain cells were studied in rats with experimental hypoxic and ischemic damage to the CNS. Changes in the expression and activity of the enzyme were detected over the course of ischemic injury indicating a possible contribution of NAD(+)-converting activity and NAD(+)-transporting processes to the pathogenesis of acute cerebral ischemic injury.

We studied apoptosis and expression of peripheral benzodiazepine receptors in granulosa cells of dominant follicles from women with endocrine sterility. The expression of peripheral benzodiazepine receptors in granulosa cells depends on the degree of granulosa cell apoptosis and type of disorders in follicular steroidogenesis, which suggests the involvement of peripheral benzodiazepine receptors into the regulation of folliculogenesis in health and disease.

Obesity is one of the urgent problems of modern health care. In the 21st century, obesity, one of the most common chronic diseases, takes on the character of a global epidemic, covering almost all countries and peoples of the world. WHO experts suggest that the number of people with obesity by 2005 compared with 2000 will increase by almost 2 times and amount to more than 300 million people. Every year, the situation is getting worse, obesity is getting younger, it becomes a problem not only for adults, but for children and adolescents. Currently, in developed countries, up to 20% of adolescents are overweight, and 15% are obese. In the Russian Federation, 5.5% of children living in rural areas and 8.5% of children in urban areas are obese. Obesity is a social problem, as it leads to early disability and reduces the average life expectancy. Finally, obesity accompanies diseases such as type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, as well as insulin resistance and hyperinsulinemia.

Objective: to study the mechanism that is responsible for impaired neuronal cell electroexcitability and viability, which is associated with modification of ADP-ribosyl cyclase in cerebral ischemic lesion, as well as the possibilities of pathogenet-ically correcting these disorders. Materials and methods. Acute cerebral ischemia was simulated in vivo on noninbred albino male rats, by ligating the right common carotid artery under general anesthesia. y-Interferon was intraperitoneally administered to the mammal in a dose of 5000 IU/kg body weight once daily for 3 days until unilateral extravasal occlusion of the common carotid artery occurred. The activity of ADP-ribosyl cyclase was evaluated by the fluorometric technique. CD38 expression in the brain cells was immunohistohemically detected. The severity of neurological symptoms was evaluated using the international NSS scale for laboratory animals. Cognitive dysfunction was recorded employing the standard test — the Morris water maze. The validity of differences was assessed by Student’s t-test and T-test, by applying STATISTICA version 6.0 (StatSoft-Russia, 1999) and BIOSTATISTICA programs. Results. Progressive neurological and cognitive deficit-induced changes occurred in the activity and expression of ADP-ribosyl cyclase/CD38 in the neuronal and glial cells in the course of brain ischemia. Neuroprotection and prevention of postischemic cognitive dysfunction were achieved by the use of y-interferon as a modifier of the brain cell expression of CD38/ADP-ribosyl cyclase.