Репозиторий Университета

© 2019, Mary Ann Liebert, Inc., publishers 2019. The purpose of our work was to study late cardiac complications after treatment for Hodgkin's lymphoma (HL) in children and adolescents. Methods: Sixty-seven patients were examined in the long term (>5 years) after chemoradiotherapy for HL according to two different programs of treatment (groups I and II). Mean total doses of radiotherapy (RT) to the mediastinum were 37.2 and 28.9 Gy, respectively. The status of the heart was assessed at the mean age of 22.7 years with electrocardiography (ECG) and echocardiography (EchoCG). Mean terms of follow-up were 16.4 and 9.5 years for group I and group II, respectively. Results: Incidence of ECG changes was equal between the groups (88% and 90%). The prevalence of signs of valvular calcifications and fibrosis was 70.9% after mediastinal doses ≥30 Gy, and 16.6% after lower doses (p = 0.002). Those changes led to considerable valvular dysfunction in four patients. EchoCG signs of pulmonary hypertension were seen in 33.3% patients of group I versus 4.8% in group II (p = 0.047). Pericardial effusion was observed in 7.4% and 5.1%, respectively (p = 1.0). Left ventricular ejection fraction decreased slightly only in two patients (one in each group). Conclusions: The RT mediastinal dose level is the important risk factor of late heart complications. Nevertheless, the differences in the rate and severity of those complications between the groups should be viewed with caution because of differences in the age at baseline and in follow-up terms. The survivors of HL should undergo life-long regular examinations of the heart status.

© 2018; Pediatria Ltd. All rights reserved. Congenital uropathies (CU) are anomalies associated with impaired patency of the upper and lower urinary tract and include congenital hydronephrosis, megaureter, primary vesicoureteral reflux (VUR), infravesical obstruction with prevalence in the pediatric population up to 1,4-2,8%. The most dangerous complication of CU is the development of kidney fibrosis in 30-60% of children combined with a persistent urinary system infection (USI). The lack of effective methods for early diagnosis and evaluation of renal parenchyma fibrosis treatment efficacy dictates the need for further search for molecular indicators of kidney injury. The article describes the study of inflammation biomarkers (interleukin 6 (IL6), inertleukin 8 (IL8), interleukin 10 (IL10)) and fibrosis (monocyte chemoattractant protein 1 (MCP1), transforming growth factor Β1 (TGFΒ1), vasculoendothelial growth factor (VEGF)) in urine in children with CU for diagnosis, monitoring and predicting the course of pathology. The study included 255 patients with various variants of CU (congenital hydronephrosis - 75, VUR - 169, infravesical obstruction - 11). The mean age of the patients was 4,3±3,2 years. The comparison group included 20 almost healthy children stratified by sex and age without USI. Biomarkers were determined by the method of enzyme immunoassay (ELISA) in the dynamics of pathology. All patients had an increase in urinary levels of proinflammatory cytokines (IL6, 8), even without clinical picture of USI. The increase in the concentration of MCP1 and TGFΒ1 in the urine is proportional to the degree and duration of VUR before its treatment, their content increased after 6 months after the correction of VUR and indicated the persistence of latent pyelonephritis and fibrosis progression. Molecular diagnosis of inflammation and fibrosis markers n the urine is a promising noninvasive method for assessing the pathological process in kidneys, the effectiveness and adequacy of the treatment.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Neonatal sepsis is one of the major causes of mortality and morbidity in newborns, greatly associated with severe acute kidney injury (AKI) and failure. Handling of newborns with kidney damage can be significantly different compared to adults, and it is necessary to consider the individuality of an organism’s response to systemic inflammation. In this study, we used lipopolysaccharide (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells damage in neonatal and adult rats. We found LPS-associated oxidative stress was more severe in adults compared to neonates, as judged by levels of carbonylated proteins and products of lipids peroxidation. In both models, LPS-mediated septic simulation caused apoptosis of kidney cells, albeit to a different degree. Elevated levels of proliferating cell nuclear antigen (PCNA) in the kidney dropped after LPS administration in neonates but increased in adults. Renal fibrosis, as estimated by smooth muscle actin levels, was significantly higher in adult kidneys, whereas these changes were less profound in LPS-treated neonatal kidneys. We concluded that in LPS-mediated AKI model, renal cells of neonatal rats were more tolerant to oxidative stress and suffered less from long-term pathological consequences, such as fibrosis. In addition, we assume that by some features LPS administration simulates the conditions of accelerated aging.

© 2018 John Wiley  &  Sons Australia, Ltd This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. Since the 1990s, when it was demonstrated by Hammel and others that liver fibrosis is reversible, researchers and physicians actively search for new antifibrotic therapies. In recent years, knowledge of liver fibrosis pathophysiology has greatly advanced and new cellular and molecular mechanisms were described. The cells that determine extracellular matrix components distribution are myofibroblasts, but their origin is diverse. They can be activated hepatic stellate cells (HSCs), portal fibroblasts (PF), or circulating mesenchymal stem cells of the bone marrow. Among large number of substrates to inhibit activation, to inhibit proliferation of myofibroblasts, and to induce their apoptosis we, chose curcumin and gliotoxin. Primarily, in the current work, we optimized the explantation culture method for isolation of hepatic myofibroblasts and received two different cultures—myofibroblasts of HSC and PF origin. Exposition of 50 μM curcumin and 0.1 μM gliotoxin was the most optimal; we observed suppression of hepatic myofibroblast activation and inhibition of their proliferation. These results extend the current knowledge of the cells within the liver fibrogenic populations and prove inhibitory influence of biologically active substances (curcumin and gliotoxin) on portal myofibroblasts.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The review discusses the issue of reflux nephropathy for specialists of the system of higher medical education: the article provides the definition, characterizes the epidemiology, risk factors for disease development in children with vesicoureteral reflux, causes and molecular mechanisms of renal fibrosis formation and progression in reflux nephropathy, markers for diagnosing and predicting the disease course.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. The lecture discusses the issue of reflux nephropathy for specialists of the system of higher medical education: the article provides the definition, characterizes the epidemiology, risk factors for disease development in children with vesicoureteral reflux, causes and molecular mechanisms of renal fibrosis formation and progression in reflux nephropathy, and markers for diagnosing and predicting the disease course. In order to control the retention of the lecture material, the text includes case problems and multiple-choice tests.

© 2018 National Research University Higher School of Economics. All rights reserved. Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is defined as an acute clinically significant respiratory deterioration characterized by evidence of new, widespread alveolar abnormalities, such as diffuse bilateral ground-glass opacification and/or consolidation, and the absence of other obvious clinical causes like fluid overload, left heart failure, or pulmonary embolism, etc. AE-IPF is subcategorized as “triggered” (where specific causes are identified, for example, infections, surgery procedures, drug toxicity, etc.) or “idiopathic” (where no specific causes are identified). In randomized trials, the annual incidence of AE-IPF is about 8%, in retrospective studies it reaches 19%. Severe forms of IPF are an important risk factor for the development of AE-IPF. In-hospital mortality from AE-IPF is more than 50%, and the average survival of patients with AE-IPF is 1-4 months. Currently, there remain no proven, effective therapies for AE-IPF. In real clinical practice patients with AE-IPF still receive high doses of systemic corticosteroids and antibiotics. Antifibrotic therapy can reduce the risk of exacerbations; it has been shown that therapy with nintedanib leads to a reduction in the number of confirmed/suspected AE-IPF by 68%. It is necessary to further study the potential methods of prevention and therapy of AE-IPF in future clinical trials.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The main reason of surgical treatment failure in cases of chronic dacryocystitis concurrent with nasolacrimal duct obliteration is scarring of the newly created ostium. This outcome is caused by the continued activity of myofibroblasts that leads to the formation of a rough scar. Mitomycin C is currently considered to be the most preferred anti-fibrotic drug. Nonetheless, contradictory evidence of the drug efficiency stimulates further research for finding alternative anti-fibro-tic therapeutics. Recently, several advances were made in developing new anti-fibrotic drugs, including monoclonal antibodies, small RNA molecules, and other gene therapy formulations, nanoparticles and small-molecule therapeutics. This review article aims to provide up-to-date information on the efficacy of mentioned agents and on prospects of their use in dacryology.

© 2018 Media Sphera Publishing Group. All rights reserved. The results of a clinical study showing the importance of surfactant proteins A and D in assessing the activity and progression of idiopathic pulmonary fibrosis and chronic lung sarcoidosis are presented. Aim. To study the clinical significance of SP-A, SP-D in assessing the activity of idiopathic pulmonary fibrosis and sarcoidosis. We examined 81 patients with morphologically confirmed diagnoses of idiopathic pulmonary fibrosis (ILF) and sarcoidosis, a control group of 20 healthy individuals. The MSCT of the thoracic organs of the chest was performed, the diffusivity of the lungs was examined, oxygen saturation was determined. In the serum, the surfactant proteins SP-A and SP-D were determined by the enzyme-linked immunosorbent assay. Results. A significant increase in SP-A and SP-D (p<0.05) was observed in patients compared with patients in the control group, a direct correlation was found with signs of activity: SP-A with alveolitis (p<0.05), SP- D with progressive fibrosis (p<0.05), inverse correlation of surfactant proteins with respiratory function indices (p<0.05). Conclusion. Serological parameters of SP-A and SP-D reflect the activity of alveolitis and the progression of pulmonary fibrosis in patients with ILF and sarcoidosis.

© 2018 Medical Education. All Rights Reserved. Chronic rhinosinusitis with nasal polyps (CRS NP) is the most prevalent ear, nose, and throat (ENT) disorder in cystic fibrosis (CF) patients. CRS NP can occur in CF children at the age of ≥ 8 months and becomes the chronic disease. Tenacious secret and bacterial infection cause obstruction, edema and hypoxia of paranasal sinuses and contribute to significant morbidity in CF patients. The active monitoring and treatment of CRS NP aimed at improvement of the aeration of paranasal sinuses, mucociliary clearance, and the control of chronic upper airway infection are necessary. Functional Endoscopic Sinus Surgery (FESS) may be the method of choice if surgical treatment is considered. FESS facilitates paranasal sinuses drainage. Due to recurrent course of CRS NP in most CF patients, lifelong follow-up by an ENT specialist and postoperative management using topical steroids and/or antibiotics are required.

© 2018 Media Sphera Publishing Group. All rights reserved. Primary sarcomas of the pericardium are extremely rare malignant tumors of the heart. The incidence of sarcoma increases after radiation therapy in the field of breast. The specific features of this case report are the difficulties in diagnostics of undifferentiated spindle-cell sarcoma of the pericardium and the connection between the disease and the radiation therapy for Hodgkin's lymphoma.

© 2018 All-Russian Public Organization Antihypertensive League. All Rights Reserved. objective. To investigate the serum levels of galectin-3 in patients with metabolic syndrome (MS) and in patients with combination of MS and left ventricular hypertrophy (LVH), as well as to define the role of this marker of fibrosis in MS. design and methods. The study included 43 patients with MS (33 patients had LVH), and 33 patients of comparable age without MS (LVH was diagnosed in 10). The level of serum galectin-3 was determined by enzyme immunoassay kits Platinum ELISA. Results. The average level of galectin-3 in the MS group was significantly higher (1,89 ± 1,71 ng/ml), compared to the group without MS (1,03 ± 0,22 ng/ml, p = 0,006). The study showed a positive correlation between the level of galectin-3 and LVH (r = 0,323, p = 0,004). The mean value of galectin-3 in patients with no evidence of LVH was 1,2 ± 0,76 ng/ml, in patients with LVH — 2,1 ± 2,02 ng/ml. conclusions. In patients with MS the level of galectin-3 was higher than in patients without MS, and in patients with MS and concomitant LVH it was higher than in patients without LVH. In patients with MS and LVH increased galectin-3 levels may indicate the severity of myocardial fibrosis and help for prognosis evaluation.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. To evaluate the role of N-terminal procollagen type III propeptide (P3NP) as a proposed marker of myocardial fibrosis in type 2 diabetes (DM2) patients. Material and methods. In the study, 2 groups of patients participated: with DM2 and non-DM2 (both n=32). All patients underwent clinical and laboratory assessment, including P3NP, electrocardiography, echocardiography. Statistics was done with Mann-Whitney criteria and Spearman correlation. Results. The level P3NP is significantly higher in DM2 patients (р<0,00001). In DM2 patients, the level of P3NP significantly correlates with increased myocardial mass of the left ventricle (р=0,00026) and myocardial mass index of the left ventricle (р=0,03685). Conclusion. Echo- and electrocardiographic signs characteristic for myocardial fibrosis (mass increase, voltage decline) in DM2 patients are concomitant with the increase of P3NP. Significant correlation of P3NP and the size of myocardium makes it to propose P3NP as one of possible markers of myocardial fibrosis in DM2 persons.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis. Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations. Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the non-inclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method. Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521-1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545-1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545-1546del, p.Y515∗ was more often found in children of the Chechen nation-odds ratio (OR) 139 (95% confidence interval 15-1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0-15.0), 4.4 (95% CI 1.8-11.1), and 351 (95% CI 17.5-7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found. Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.