Репозиторий Университета

© 2018 Dynasty Publishing House. All rights reserved. The article presents a clinical case of a patient with genetically confirmed Alagille syndrome (ALGS) with marked delay of physical development that did not correspond to the severity of liver damage. Alagille syndrome (ALGS) is a rare hereditary disease with underlying hypoplasia of the intrahepatic bile ducts manifested by cholestasis syndrome in the first weeks of life. Developmental delay is characteristic for cholestatic diseases of the liver, including ALGS, which is conditioned by impaired absorption of fats and fat-soluble vitamins in the intestines. But growth delay and underweight in this syndrome often do not correlate with the severity of cholestatis syndrome, and causes of their development remain unstudied. Cholestatis syndrome was moderate, and clinical signs of liver cirrhosis were absent. Intense skin itching, greatly disturbing not only the baby's wake period but also sleep, along with marked height and weight deficit were indications for liver transplantation at the age of 4 years, after which a fast normalisation of the parameters of physical development was noted. This clinical case study permits to hypothesize that developmental delay in children with ALGS is conditioned by chronic cholestatic liver damage, irrespective of the severity of its clinical presentation.

© Bionika Media Ltd. Objective. To present an analysis of the data available in the literature on the role of extracellular fetal DNA (fDNA) in predicting the great obstetric syndromes. Material and methods. Literature sources published in databases, such as Pubmed and Scopus, were sought. Results. There is evidence indicating that increased maternal blood DNA levels can be used as a predictive marker for pregnancy complications, such as preeclampsia, preterm birth, and fetal growth retardation. The most likely mechanism for increasing maternal blood fDNA is the strengthening of apoptotic, necrotic, and inflammatory processes in the placenta. However, not all studies confirm that there is a relationship between the development of the great obstetric syndromes and higher fDNA concentrations. Conceivably, the contradictions are due to the use of a number of procedures to determine fDNA, which limit sampling by sex and rhesus factor. Also, there is no consensus on the time when its concentration starts to increase; the influence of confounding factors has not been investigated. Conclusion. Maternal blood extracellular fDNA is a promising marker for predicting the great obstetric syndromes. There is a need for further investigations, by using the procedures that do not limit sampling and by taking into account the factors that influence the maternal blood concentration of extracellular fDNA.

© 2018 Ima-Press Publishing House. All rights reserved. Cognitive impairment (CI) is a basis for the clinical presentation of chronic cerebral ischemia (CCI). However, the role of the mechanisms of inflammation and angiogenesis in the origin of CI is unclear, as is its relationship to the number and localization of foci during a neuroimaging examination. Objective: to investigate the relationship between the presence of CI, focal brain tissue changes, and the plasma and serum levels of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) in patients with CCI. Patients and methods. Examinations were made in 59 patients with CCI and in 20 apparently healthy individuals. The investigators evaluated the cognitive status using the Mini-Mental State Examination (MMSE) and the clock drawing test), performed brain magnetic resonance imaging (MRI), duplex scanning of cerebral vessels, and determined laboratory indicators: the serum levels of MCP-1 and C-reactive protein, and the serum and plasma concentrations of VEGF. Results. The patients with CI were found to have higher values of inflammatory markers, lower serum and plasma concentrations of angiogenic factors, and a greater number of focal changes on MRI than those without CI (5.06±0.23 and 2.36±0.3 scores, respectively; p(0.05). Imbalance of angiogenic and antiangiogenic factors can cause disease progression and moderate vascular CI in patients with CCI.

© 2018, Pediatria Ltd.. All rights reserved.  Objective of the research – to reveal the correlation between neurochemical criteria in the neonatal period and the consequences of severe hypoxic hemorrhagic CNS lesions in children according to catamnesis data. Materials and methods: researchers analyzed 54 cases of newborns of different gestational age (GA) that were in the ICU after birth due to severe condition; all newborns had combined hypoxic hemorrhagic brain lesion detected by neurosonography – periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH) of various severity. Catamnesis follow-up was performed up to 2–2,5 years of age. The control group consisted of 20 newborns, comparable in GA, body weight at birth, with an Apgar score of at least 6 points in the 1st minute of life and without changes in neurosonography. In the neonatal period, serum concentrations of S100, BDNF, VEGF, ALCAM, DR5 were studied in dynamics using the quantitative ELISA (Enzyme Linked Immuno Sorbent Assay) according to a standard protocol. Results: the concentration of factors contributing to destructive changes in tissues (S100, DR5, ALCAM) in the serum, was in inverse correlation with the level of VEGF and BDNF. The latter had a direct correlation relationship. VEGF directly correlated with CNTF by the end of the 2 nd week of life. Results of catamnesis follow-up: 43 children diagnosed with cerebral palsy, 25 with spastic diplegia, 18 with spastic tetraparesis, and 11 without evident motor disorders. In 28 children I–III level of motor disorders was determined according to GMFS, in 26 children – IV–V level. At the age of 2 years, all children underwent MRI of the brain and gliio-atrophic changes were detected. Significant differences in the implementation of neurological consequences were found between the number of children with grade I and II IVH and PVL and III–IV degree IVH and PVL. Conclusion: children with PVL and IVH III–IV degree have a high risk of severe neurological outcomes – spastic tetraparesis, impaired motor activity by GMFS IV–V level, mental retardation and symptomatic epilepsy.

© 2018, SPb RAACI. Periodontal disease, including gum disease, gingivitis, periodontitis and periodontal disease is frequently associated with progressive loss of bone and soft periodontal tissues. Recent studies suggest effectiveness of platelet-derived growth factor, fibroblast growth factor and other growth factors, which may stimulate regeneration of connective and bone tissue. A number of cytokines and growth factors participate in regulation of angiogenesis, but vascular endothelial growth factor (VEGF) is the most powerful agent, acting directly on the vascular endothelium. VEGF detected in saliva and endothelial cells of periodontium. VEGF plays a dominant role both in periodontal health maintenance as well as in chronic inflammatory periodontal disease. The aim of this work was to develop implementation of VEGF in periodontology, and a search for laboratory markers of therapeutic efficiency in periodontitis. We observed 19 patients aged 53-79 years with I-II grade periodontitis. In frames of periodontal therapy, the patients used a drug "Rebon. Gel for Gum" ("GF group", Russia). The drug represents a composition of bioresorbable carbohydrates on the basis of carboxymethylcellulose, forming the cellular basis for similar extraclean matrix. It contains different sodium, potassium, phosphorus, chlorine salts in order to balance the tissue pH, and a complex of glycated recombinant polypeptides identical to cytokines and human growth factors. ELISA method was used in the biological samples for detection of VEGF, human isoform A-165 ("SCI store" Ltd., Russia), and IFNγ (JSC "Vector Best", Russia). All our patients noted a decrease in pain after the treatment, as well as a significant acceleration of healing processes in oral cavity. Observation of the oral cavity state showed good dynamics and acceleration of bone tissue regeneration. After the treatment course, the level of IFNγ increased from 14.48 to 27.45 pg/ml. The difference before and after treatment values was significant (p = 0.022), despite a sufficient range of measured values. VEGF in gingival fluid showed a large scatter of values, from 26 to 279 pg/ml before treatment, and 16 to 198 pg/ml after treatment. Generally, a tendency for VEGF decrease was observed after treatment. To diagnose the current state of the periodontium, an importance of analyses of the gingival sulcus fluid is actual. The developed diagnostic approaches based on measuring the IFNγ, VEGF levels in screening and monitoring regimens help to provide a more effective treatment. Introduction of a complex preparation with growth factors and peptidoglycan-recognizing protein seems to accelerate epithelialization and regeneration of connective and bone tissue.

© 2018, Bionika Media Ltd. All rights reserved. The implementation of the INTERGROWTH-21st fetal growth and newborn size for gestation age standards into clinical practice in Russia were discussed and debated. The INTERGROWTH-21st Project was implemented in more than eight countries from 2009 to 2018. All study protocols and primary findings are available online (intergrowth21. org). Briefly, eight diverse urban populations living in demarcated geographical areas were selected where: environments were free from major known pollutants; altitude was less than 1600 m; most women accessed antenatal and delivery care in institutions; mean birth weight was greater than 3100 g; rates of low birth weight (< 2500 g) were less than 10%, and perinatal mortality was less than 20 per 1000 births. The INTERGROWTH-21st study comes as a high-quality response to the common dilemma of lack of standardization in fetal growth assessment. Its use should be encouraged among Russian specialists in maternal-fetal medicine, obstetricians and radiologists.

© 2018 by the MediaSphere. The materials of the National Consensus reflect the modern domestic and international experience on this issue. Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation. A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child's height is < –2.0 SDS, if the difference between the child's height SDS and child's midparental height SDS exceeds 1.5 SDS and/or a low growth velocity. The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation. The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day. With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum. GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphy-seal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient's desire and his parents / legal representatives satisfied with the achieved result of the final height. Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation. If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.

© 2018 John Wiley  &  Sons Ltd. While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.