[Clinical guidelines «Obesity in children¼].

Childhood obesity is an urgent problem of pediatric endocrinology due to the widespread occurrence, the development of metabolic complications and their steady tracking into adulthood. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of obesity, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

[Clinical guidelines «Precocious puberty¼].

The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target indicators of final growth and prevent social deprivation. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of рrecocious puberty, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

[The social anamnesis, conditions of life and life-style of pregnant women with syphilitic infection].

The article presents the results of analysis of characteristics of social behavior, life conditions and life-style of pregnant women with syphilitic infection. The sampling included 647 female pregnant patients actually ill with syphilis or having this disease in the past that were accepted to maternity houses of Krasnoyarsk in 2004-2014. The three groups of women with syphilitic infection were organized on the basis of remoteness of diagnosis of disease and results of complex of serological reactions during pregnancy. The presented data testify late diagnostic of mentioned pathology and significant percentage of hidden forms of infection course. The characteristics of "social portrait" of women with syphilitic infection during pregnancy are early beginning of sexual life (prior to 18 years in every 5-6 woman), predominantly school education and specialized secondary education, belonging to working specialties, availability of harmful habits and chronic diseases (about 50%) non-registered marriage. The study established no reliable facts of non-adapted social behavior of pregnant women with syphilis.

[Hypoglycemia in neonates: a review of the literature and a case report].

Hypoglycemia in the neonatal period is one of the urgent problems of pediatric endocrinology. The main factors that lead to disruption of carbohydrate homeostasis are generally known, but the issues of neonatal hypoglycemia continue to be actively studied. In the last few years, the effect of low blood glucose on brain neurons has been studied, the issues of glycemia monitoring in the first days of life have been outlined, and strategies for managing newborns with hypoglycemic syndrome are being discussed.

[Development of blood-brain barrier under the modulation of HIF activity in astroglialand neuronal cells in vitro]. / Osobennosti formirovaniia gematoéntsefalicheskogo bar'era pri moduliatsii aktivnosti HIF v kletkakh astroglial'noi i neironal'noi prirody in vitro.

Barriergenesis is the process of maturation of the primary vascular network of the brain responsible for the establishment of the blood-brain barrier. It represents a combination of factors that, on the one hand, contribute to the process of migration and tubulogenesis of endothelial cells (angiogenesis), on the other hand, contribute to the formation of new connections between endothelial cells and other elements of the neurovascular unit. Astrocytes play a key role in barriergenesis, however, mechanisms of their action are still poorly examined. We have studied the effects of HIF-1 modulators acting on the cells of non-endothelial origin (neurons and astrocytes) on the development of the blood-brain barrier in vitro. Application of FM19G11 regulating expression of HIF-1 activity and GSI-1 suppressing gamma-secretase and/or proteasomal activity resulted in the elevated expression of thrombospondins and matrix metalloproteinases in the developing blood-brain barrier. However, it caused the opposite effect on VEGF expression thus promoting barrier maturation in vitro.

Expression of Glutamate and Glutamine Transporter Proteins in Neurovascular Unit Cells In Vitro.

Glutamine transporter protein SLC1A5 and glutamate transporter protein EAAT2 responsible for cell-cell communication and energetic coupling were studied using in vitro model of multicellular neurovascular unit consisting of astrocytes, neurons, and endotheliocytes under standard conditions and during chemical hypoxia in vitro. Hypoxic damage to the neurovascular unit cells increased the number of SLC1A5-expressing cells and reduced the number of EAAT2-expressing astrocytes. Metabolic uncoupling in the neurovascular unit cells under hypoxic conditions resulted from abnormal expression of glutamine and glutamate transporter proteins, which is indicative of impaired glutamine and glutamate transport.

[CURRENT OPPORTUNITIES IN THE IDENTIFICATION OF NOVEL MOLECULAR TARGETS FOR PHARMACOLOGICAL CORRECTION OF BLOOD-BRAIN BARRIER PERMEABILITY].

Review covers current achievements in the methodology of target discovery and validation for the development of drugs restoring structural and functional integrity of the blood-brain barrier (BBB) in cases of brain injury and neuroinflammation. Some new targets (in the context of BBB permeability) are discussed, which are involved in the regulation of signal transduction involving HIF-1, JNK, NF-κB, Rac, 1 etc., expression of tight-junction proteins, and activity of enzymes producing molecules with pro-inflammatory effects in the BBB cells.

Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study.

Acute respiratory infections (ARI) still represent a big challenge for paediatricians, especially in those children defined as "ailed" as they are more susceptible to such kinds of disease. In this paediatric population, the immune system is still under-developed with an evident alteration in cytokine levels. A clinical study was carried out in 5 sites in Russia with the intention to enroll children particularly susceptible to contract respiratory infections (defined as "ailing"), assigning them to a treatment group with pidotimod in comparison with a control group, treating them for 30 days and observing the reduction in the number of ARI episodes throughout the follow-up period (6 months). Moreover, changes in serum immunological markers were evaluated at baseline and 30 days after treatment discontinuation. One hundred and fifty-seven ailing children were enrolled and assigned to two arms: a main pidotimod treatment group or a control group. The percentage of incidence of ARIs in the observation period at three different time points was statistically significant (p < 0.05). At the end of the follow-up period (after 6 months), ARIs had developed in 72 children (92.3%) in the main group and in 79 patients (100%) in the control group. Concerning changes of the immunological markers, the treatment group showed a better profile of normalization compared to the control group. The 30-day pidotimod therapy course led to improvement/reduction in the rate of acute respiratory infection recurrence in ailing children within a 3-month period, with a quick elimination of symptoms and signs of infection and, as a result, a faster recovery. The normalisation of the content of the pro-inflammatory cytokine interleukin-8 confirmed the immune-modulatory effect of the investigational drug, underlying its prophylactic effect.

[Current concepts of perinatal ischemic injury in the brain neurovascular unit: molecular targets for neuroprotection].

Perinatal hypoxic-ischemic brain injury is a relevant medical and social problem. Among many pathological processes in the neonatal period perinatal hypoxic-ischemic injury is a major cause of further hemorrhage, necrotic and atrophic changes in the brain. This review presents recent data on the basic mechanisms of the hypoxic-ischemic brain injury along the concept of neurovascular unit (neurons, astrocytes, endothelial cells, pericytes) with the focus on alterations in cell-to-cell communication. Pathological changes caused by ischemia-hypoxia are considered within two phases of injury (ischemic phase and reperfusion phase). The review highlights changes in each individual component of the neurovascular unit and their interactions. Molecular targets for pharmacological improvement of intercellular communication within neurovascular unit as a therapeutic strategy in perinatal brain injury are discussed.

[NAD+-converting enzymes in neuronal and glial cells: CD38 as a novel target for neuroprotection].

The review contains current data on molecular mechanisms which control NAD+ homeostasis in brain cells. It also deals with the role of NAD+-converting enzymes in regulation of functional activity, viability and intercellular communication of neuronal and glial cells. Special attention is paid to involvement of CD38 into regulation of NAD+ levels in brain cells in normal and pathological conditions.

Perinatal hypoxic and ischemic damage to the central nervous system causes changes in the expression of connexin 43 and CD38 and ADP-ribosyl cyclase activity in brain cells.

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.

[The component composition of the body in children with progressive obesity].

The aim of the investigation was to determine the major components of body mass in obese children. Two hundred and thirty-four children aged 8-16 years, including 181 healthy children and 53 obese children, were examined. The components of body mass in obese children were comparatively analyzed, by taking into account gender, age, and the disease seventy, which Indicated that the adipose tissue was the major component of the body, greatly dominating over muscular and bony components with its increase in progressive disease (up to 280 and 448% of the normal values in second- and third-degree obesity, respectively). The absolute content of fat as the body's major component in overweight children has no great gender differences. In children, obesity progression is accompanied by a statistically significant reduction in absolute body mass and in the proportion of an osseal component in younger age (8-10 years) groups.

Prevalence of type 2 diabetes in northern populations of Siberia.

In the first part of the study the prevalence and incidence of diagnosed Type 2 diabetes among adult rural populations of southern, central and northern areas of the Krasnoyarsk region of Siberia is compared. The six-year mean incidence of diabetes in the southern area was 0.86 per 1000 (95% CI: 0.66-1.06), in the central area this incidence was 0.79 (0.57-1.01). In contrast, in the northern area the mean Type 2 incidence among indigenous population was 0.16 per 1000 (0-0.43) and among aliens it was 0.38 (0.22-0.54). The age-standardised Type 2 diabetes prevalence in the population of southern and central areas were 10.23 (9.55-10.-92) and 10.77 (9.99-11.55), respectively. In the northern area among aliens it was 8.98 (8.18-9.78) and among indigenous peoples only 2.54 per 1000 (1.46-3.62). The second part of this study consists of a population based survey to determine the prevalence rate of Type 2 diabetes among 596 Evenks and 306 alien inhabitants in Evenkia (82% eligible participants of Baikit district). No cases of glucose intolerance were found among Evenks in this study and one case of Type 2 diabetes was confirmed among aliens (prevalence rate 3.27 per 1000). These data indicate that Type 2 diabetes is still rare among northern indigenous populations of Siberia and that diabetes in northern alien populations is less prevalent than among peoples of central and southern areas of Siberia.