Association of PRDM16 rs12409277 and CtBP2 rs1561589 gene polymorphisms with lipid profile of adolescents.

Introduction: Positive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Our aim was to analyze the association of PRDM16 gene (rs12409277) and CtBP2 gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents. Material and methods: Our study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded. Results: We did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (p = 0.001) and LDL cholesterol (p = 0.008) levels compared to all other groups of genotypes. Conclusions: Our study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.

Effects of carvedilol on left ventricular function and oxidative stress in infants and children with idiopathic dilated cardiomyopathy: a 12-month, two-center, open-label study.

OBJECTIVES: This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. METHODS: Hospitalized children aged 62.5 kg) was associated with significant decreases from baseline in systolic BP (130 [4] vs 123 [3] mm Hg; P<0.05), diastolic BP (85 [4] vs 77 [4] mm Hg; P<0.05), and HR (81 [4] vs 65 [4] bpm; P<0.001) after the first month of addition to standard therapy. At 6 months, there were significant improvements from baseline in EF (37.2% [2.4%] vs 50.2% [2.3%]; P<0.001) and FS (18.37% [2.00%] vs 23.58% [0.90%]; P<0.001). Modified NYHAC class was significantly improved in 80% of children (2.9 vs 2.3; P<0.001) at 12 months. The highest dose of carvedilol (0.8 mg/kg/d in children 62.5 kg) was well tolerated in all 21 children. No serious AEs that necessitated study drug discontinuation (tiredness, headache, vomiting) were observed. At baseline, mean (SE) erythrocyte SOD activity (2781 [116] vs 2406 [102] U/g Hb; P<0.05) and GR activity (5.3 [0.3] vs 3.0 [0.2] micromol nicotinamide adenine dinucleotide phosphate [NADPH]/min/g Hb; P<0.001) were significantly higher in children with DCM who received standard therapy compared with healthy controls.CAT activity (12.7[0.9] vs 18.5 [1.0]U/g Hb; P<0.001) was significantly lower, while GSH-Px was unchanged. At 6 and 12 months of therapy, carvedilol plus standard treatment was associated with significant decreases from baseline in SOD (2516 [126] and 2550 [118], respectively, vs 2781 [116] U/g Hb; both, P<0.001) and GR (4.7 [0.3] and 4.1 [0.2], respectively, vs 5.3 [0.2] micromol NADPH/min/g Hb; P<0.05 and P<0.001) and increased CAT (16.9 [1.0] and 16.4 [0.7], respectively, vs 12.7 [0.9] U/g Hb; both, P<0.001). CONCLUSIONS: These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children 62.5 kg) were found to have significant improvements in LVF and symptoms of HF. Twelve months of carvedilol therapy was associated with antioxidant enzyme activities near those observed in healthy children.

Cardiovascular risk factors and blood pressure in a primary care unit: Yugoslav Study of the Precursors of Atherosclerosis in School Children (YUSAD).

OBJECTIVES: The presence of cardiovascular risk factors in children may be important in the development of atherosclerosis in adulthood. Adequate control of blood pressure is a cornerstone in atherosclerosis prevention. The aim of the Yugoslav Study of the Precursors of Atherosclerosis in School Children (YUSAD) was to identify risk factors for elevated blood pressure in school children. METHODS: The YUSAD study is a multicentre follow-up study comprised of two cross-sectional surveys conducted five years apart. At baseline, 10-year-old children (3226 boys and 3074 girls [n=6300]) were randomly selected during periodical visits to primary health care centres. The risk factors measured were heart rate, weight, body mass index (BMI), waist-to-hip ratio, grade point average and current smoking status. RESULTS: Significant age and sex differences were identified in systolic blood pressure, diastolic blood pressure and all investigated independent variables. In a multivariate analysis, diastolic blood pressure in 10-year-old boys was directly and significantly related to total cholesterol and height, whereas it was inversely related to weight. At follow-up, in the multivariate model, only BMI was a significant predictor of diastolic blood pressure in boys. In girls at baseline in the multivariate regression analysis, the only significant predictor of diastolic blood pressure was total cholesterol. In 15-year-old girls, diastolic blood pressure was significantly and directly related to BMI and heart rate, whereas it was inversely related to weight. For both 10- and 15-year-old male and female participants, none of the variables by multivariate analysis were a significant predictor of systolic blood pressure. CONCLUSIONS: Age, sex, heart rate, cholesterol and weight are the most important predictors of blood pressure in school children.

Effect of posture on heart rate variability spectral measures in children and young adults with heart disease.

BACKGROUND: Reduction of heart rate variability as a consequence of heart disease and postural change has been well documented. However, the data on the effect of postural change in pediatric patients are incomplete and the effect is not fully understood. The aim of the study was to investigate effect of postural change on heart rate variability in relation to the extent of severity of heart disease. METHODS: The dependence of heart rate variability on posture in 41 children and young adults (8-20 years) with heart disease has been investigated and compared with control. Short-term electrocardiograms (ECGs) were assessed in supine rest and active standing, and spectral measures of heart rate variability were determined. RESULTS: Two types of response to the change of supine to standing posture were determined in both healthy and diseased subjects. In majority of subjects, the increased heart rate induced by standing was accompanied by a decrease in high-frequency power. However, in about 30% of all subjects, increased heart rate during standing was accompanied by an increased high-frequency power. Independently of posture and disease, high-frequency and low-frequency power were positively correlated. In subjects characterized by a reduction of heart rate variability in standing, the high-frequency power in both postures is reduced in diseased subjects compared to control. CONCLUSIONS: These results demonstrate that in this age range, the response to posture is not unique because of the difference in high-frequency power, which implies a variety of vagal modulations of heart rate.

Anthropometric and lipid parameters trends in school children: one decade of YUSAD Study.

INTRODUCTION: Athersclerosis is a multifactorial disease that begins in childhood. There are few reports regarding influence of risk factors on the atherosclerotic processes in early period of life and adolescence. OBJECTIVE: The aim of this study was to present and analyze risk factor trends in school children over a 10-year period that were included and followed-up by the Yugoslav Study of Atherosclerosis Precursors in School Children (YUSAD Study). METHODS: There were three examinations of selected population from 13 centres. The first examination was performed when children were 10 years of age (first group; N = 6381 participants), the second examination on the same population when they were 15 years of age (second group; N = 5017) and third when children were 19/20 years of age (third group; N = 1293). Evaluated parameters included: BMI, waist circumference (WaC) and lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride). RESULTS: A significant elevation of values (p < 0.001) of BMI, WaC and triglycerides and a significant decline (p < 0.001) of total cholesterol and LDL cholesterol in boys over 5 and 10-year period was noticed. There was a significant elevation (p < 0.001) of BMI, WaC and HDL values and a significant decline in LDL cholesterol values in girls over the 5 and 10-year period. CONCLUSION: Our results point out that girls between 10 and 19/20 years have a better lipid profile during growth. It should be stressed out that childhood and adolescence can be more beneficial in the observation of risk factor influences on pathological, genetic and clinical levels.

Physical activity evaluation in Yugoslav Study of the Precursors of Atherosclerosis in School Children - YUSAD study.

INTRODUCTION: It is observed that there is a lack of physical activity and exercise in children, stressing higher prevalence of childhood obesity. The purpose of the study was to evaluate duration of physical activity in a child population and correlation of dynamics in physical activity during 5 years of follow-up in the same population. MATERIAL AND METHODS: We evaluated 3243 school children from 12 regional centres across Serbia. The first examination was done when the children were 10 years old (baseline group), while the second examination was done on the same population when children were 15 years old. Physical activity was classified as recreational activity after school. We analysed 3 groups regarding physical activity: a group of children who were physically active less than 1 hour per day (group I), a second group active from 1 hour to < 3 hours per day (group II), and a third group active ≥ 3 hours per day (group III). RESULTS: In our study we have found on examination that the majority of children were physically active between 1 and 3 hours per day. Our results indicate that there is significant movement from groups I and III toward group II on the second examination regarding the proportion in the baseline group. There is a significant increase in the number of children in group I as they get older. CONCLUSIONS: School children in Serbia are physically active predominantly between 1 and 3 hours per day at the age between 10 and 15 years.

[Surgery for coarctation of the aorta in infants younger than three months]. / Hirursko lecenje koarktacije aorte kod odojceta uzrasta do tri meseca.

INTRODUCTION: Recurrent coarctation is a complication which is seen at a consistent rate following repair for coarctation of the aorta in young infants. OBJECTIVE: This retrospective analysis was carried out to compare the results between resection with end-to-end anastomosis (ETE), and resection with extended end-to-end anastomosis (E-ETE), in this age group during late follow-up period. The role of ductus arteriosus is not clearly defined and the second objective of this study was to analyze intimal thickening in aortic coarctation. MATERIAL AND METHODS: From 1999 to 2003, 45 patients less than 3 months of age underwent repair of aortic coarctation. Mean age was 24 days (2-89 days), average weight was 3.5 +/- 0.6 kg (2.4-5.2 kg). The method of repair was ETE in 14 (31.1%) patients, E-ETE in 29 (64.4%) patients and other techniques were applied in 2 cases. Demographic, morphometric, clinical and operative variables were analyzed for correlation with recurrent arch obstruction. In order to characterize the components of intimal thickening in coarctation, narrowed segments of aorta resected from 16 neonates during surgery were examined immunocytochemically and by electron microscopy. For light microscopy, the specimens were dehydrated in graded ethanol (70-100%), cleared in xylol and embedded in paraffin. Immunocytochemical staining was performed in 5 microm sections from formaldehyde-fixed paraffin-embedded blocks, using a labeled streptavidin-biotin method with an LSAB kit (Dako). RESULTS: Early mortality was 6.7% (CI 95%, 2.9%-10.4%). All early deaths (3 patients) occurred in infants with associated ventricular septal defects (p<0.05). The mean follow-up for all patients was 30 +/- 21 months (range 1.5-63 months). During mean follow-up of 2 months, recurrent arch obstruction was diagnosed in 9 patients (21.4%). Two patients with associated complex heart defects died before re-intervention, one had mild gradient on catheterization (20 mm Hg) and one is waiting for catheterization. Five patients were reoperated and the mean time to re-intervention was 4 months (range 2.6-6 months). Kaplan-Meier freedom from recoarctation was 78.1 +/- 6.4% at 5 years in the whole group. Freedom from recoarctation was 60.6 +/- 15.4% at 25 months in ETE group and 86.2 +/- 6.4% at 60 months in E-ETE group (p=0.062). Factors associated with recoarctation, obtained by univariable Cox regression, included abnormal right subclavian artery (p=0.003), hypoplastic proximal transverse aortic arch (Z < or = -2, p=0.025) and weight at operation < or = 3 kg (p=0.02). Abnormal origin of the right subclavian artery was the only independent predictor of recoarctation obtained by multivariable Cox regression analysis. DISCUSSION: All examined specimens had intimal thickening of the posterior aortic wall, with accumulation of smooth muscle cells (SMC) with alpha smooth muscle actin (alpha-SMA) and vimentin-immunoreactivity (but not desmin and MHC) and also expressed PCNA and S-100. In the inner media of the anteromedial wall of the aorta, all specimens had large number of SMC expressing desmin and MHC. SMC in the inner media exhibit contractile phenotype and their origin could be ductal. CONCLUSION: Both procedures are effective for coarctation repair in young infants. Risk of recoarctation is a function of the complex anatomy of the arch, while residual ductal tissue may play a significant role.

[Results of treatment of cyanotic heart defects in children]. / Rezultati lecenja cijanogenih mana srca kod dece.

Cyanotic heart diseases are relatively rare, but they are severe and heterogeneous congenital heart diseases, which require complex surgery. Development of different advanced surgical procedures, such as arterial switch operation (ASO), Fontan and its modifications, Norwood etc. operations, as well as better perioperative care significantly improved survival rate and quality of life of these children. The study group included 308 children treated for cyanotic heart disease in Yugoslavia, in the period January 2000 to July 2004. Some of them (239, 77.6%) were treated at the University Children's Hospital in Belgrade, and others (69, 22.4%) in different institutions abroad. The age of the operated patients varied between 1 day and 19 years (median 12 months). The patients (pts) were divided into four groups, according to the disease and type of the operation. In the whole group of 308 patients treated due to cyanotic heart disease, there were 232 (75.3%) cases with open heart surgery and 76 (24.7%) with closed procedures. The mortality rate was significantly different between disease/operation groups, and age groups. Average mortality rates differed from 11.8% for palliative procedures to 12.5% for complete corrections. Mortality rate and achieved surgical results in treatment of children with cyanotic heart diseases were significantly worse than those published by leading cardiac surgery centers in the world. However, there is a clear tendency in introducing new surgical procedures, lowering the age at which the operation is done and decreasing the mortality rates.