Investigation of irisin's role in pubertal onset physiology in female rats.

OBJECTIVE: The timing of pubertal development is closely related to metabolic status and energy reserves. It is thought that irisin, which is involved in the regulation of energy metabolism and is shown to be present in the hypothalamo-pituitary-gonadal (HPG) axis, may play a role in this process. In our study, we aimed to investigate the effect of irisin administration on pubertal development and HPG axis in rats. DESIGN-METHODS: 36 female rats were included in the study were divided into 3 groups: 100 ng/kg/day irisin treatment group (irisin-100), 50 ng/kg/day irisin treatment group (irisin-50), and control group. On the 38th day, serum samples were taken to determine levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and irisin. Brain hypothalamus samples were taken to determine levels of pulsatile gonadotropin-releasing hormone (GnRH), kisspeptin, neurokinin-B, dynorphin (Dyn), and makorin ring finger protein-3 (MKRN3). RESULTS: Vaginal opening and estrus were seen firstly in the irisin-100 group. At the end of the study, the highest rate of vaginal patency was found in the irisin-100 group. Hypothalamic protein expression levels of GnRH, NKB and Kiss1 in homogenates; serum FSH, LH, and estradiol levels were the highest in the irisin-100 group, followed by the irisin-50 and control groups, respectively. Ovarian sizes were significantly greater in the irisin-100 group compared to the other groups. The hypothalamic protein expression levels of MKRN3 and Dyn were the lowest in the irisin-100 group. CONCLUSIONS: In this experimental study, irisin triggered the onset of puberty in a dose-dependent manner. Irisin administration caused the excitatory system to dominate in the hypothalamic GnRH pulse generator.

Association of Myeloperoxidase Gene Polymorphism With Iron Deficiency Anemia in Turkish Children.

This study was performed to investigate the gene polymorphisms of the myeloperoxidase (MPO) enzyme and to determine whether MPO gene polymorphisms influence the response to iron therapy in pediatric patients with iron deficiency anemia (IDA). In this case-control study, 50 Turkish children with IDA and 50 healthy controls were enrolled. Three MPO gene alleles were selected for genotyping in the study: GG, AG, and AA. The relationships of alleles with IDA were analyzed and compared in patients and controls. Pretreatment and posttreatment laboratory parameters and gene polymorphisms were compared in the patient group. There was a significant difference between patients with IDA and controls regarding genotype frequencies of the AA, GG, and AG alleles (P=0.005). However, the AG allele was found to be associated with variations in hemoglobin, red blood cell, hematocrit, mean corpuscular volumes, and mean corpuscular Hb concentrations levels. The frequency of AA, GG, and AG alleles of the MPO gene was potentially associated with changes in iron metabolism and the AG allele led to variations in various hemogram parameters.

Assessment of motor development using the Alberta Infant Motor Scale in full-term infants.

The Alberta Infant Motor Scale (AIMS) is a well-known, norm-referenced scale that evaluates the gross motor development of children from birth to 18 months. The aim of the study was to compare the Canadian norms with the AIMS scores of a Turkish sample of infants, and to investigate whether the current reference values of the AIMS are representative for Turkish full-term infants. The study was conducted with 411 Turkish infants of both sexes (195 girls and 216 boys), born with gestational age 38 weeks and older, weighing ≥2500 g at birth. Motor performance of all the cases at different ages were assessed with the AIMS which was used by a physiotherapist. The mean AIMS scores of Turkish infants were compared with the norm values of the original AIMS established in a Canadian sample of infants. The results showed no statistically significant differences between the AIMS scores of Turkish and Canadian infants during the first 18 months of life except at 0- < 1 and 2- < 3 months of age. The AIMS scores were significantly lower in Turkish infants than in Canadian infants at 0- < 1 (p=0.025) and 2- < 3 (p=0.042) months of age. In conclusion, the AIMS can be used in Turkish children to assess gross motor development, especially after 4 months of age. However, this paper was presented as a preliminary study to compare AIMS results between Turkish and Canadian infants, and further studies are needed to realize the Turkish validation of AIMS.

Serum catalase, thiol and myeloperoxidase levels in children passively exposed to cigarette smoke.

BACKGROUND: Free radicals found in cigarette smoke can harm all tissues and cellular structures in the human body. Passive smoking increases free radical production, leads to the depletion of antioxidants and increases oxidative stress which causes lipid peroxidation. Many studies have been conducted to determine the effects of passive smoking on antioxidant enzymes and lipid levels in adults, but pediatric studies on this topic are few. In our study, we compared the levels of antioxidants, oxidants, total and LDL cholesterol in children exposed to passive cigarette smoking with a healthy control group that was not exposed to passive smoking. METHODS: A total of 41 children (4-17 years of age, 24 girls and 17 boys) exposed to passive smoking and 18 healthy girls and 12 healthy boys were included in this study. Secondhand smoking was confirmed via measurement of the cotinine/creatinine ratio. Various sociodemographic characteristics of patients were recorded. The levels of catalase, thiol, myeloperoxidase were measured to determine the antioxidant and oxidant levels in children, while the levels of total cholesterol and LDL cholesterol were measured to determine the alterations in lipid profile. RESULTS: The groups were similar in regard to demographic characteristics. Myeloperoxidase levels were significantly higher in the passive cigarette smoking group compared to the non-exposure group; however, catalase and thiol levels were similar. In regard to lipid profile, the levels of total cholesterol and LDL cholesterol were also similar in those with and without exposure to passive smoking. CONCLUSIONS: Our findings suggest that the effects of passive smoking initially influence oxidants (MPO), but not antioxidants (thiol and catalase). However, it is apparent that passive smoking adversely affects oxidative balance in children and this may lead to the development of various diseases which could cause significant morbidity and mortality.

Risk factors for childhood obesity: Do the birth weight, type of delivery, and mother's overweight have an implication on current weight status?

BACKGROUND: The aim of this study was to identify risk factors, including the type of delivery, breastfeeding and its duration, birth weight, the timing of solid food introduction, the mother's education level at birth, and smoking status during pregnancy, that are associated with obesity in children living in Istanbul. METHODS: This study involving 4990 healthy children aged 2-14 years, at an outpatient clinic in a tertiary care hospital from June 2012 to July 2014. RESULTS: The overall rates of overweight and obesity in children were 13.1% and 7.8%, respectively. Results demonstrated that 44.5% of children were delivered by caesarean section. In all age groups, 7.8% of children delivered by caesarean section were obese compared with 7.9% of children born vaginally. No significant association between caesarean section delivery and obesity in childhood was found in our study [odds ratio (OR)=0.98, 95% confidence interval (CI)=0.64-2.87, P=0.454]. There was also no association between duration of breastfeeding and the introduction of solid foods before 4 months or after 6 months of age and childhood obesity (OR=0.95, 95% CI=0.69-1.3, P=0.771; OR=0.99, 95% CI=0.64-1.53, P=0.261). Regression analyses revealed that children with birth weights greater than 3801 g or those with maternal body mass index (BMI) equal to or greater than 30 had an increased risk of being obese or overweight (OR=1.78, 95% CI=1.19-2.65; OR=3.95, 95% CI=1.94-5.81). CONCLUSIONS: This study demonstrated that increased birth weight and maternal BMI are significant risk factors for obesity in children living in Istanbul, Turkey. No relation between caesarean section delivery and childhood obesity was found in this study.

Serum oxidative stress parameters and paraoxonase-1 in children and adolescents exposed to passive smoking.

BACKGROUND: Exposure to secondhand smoke is too common in many countries. The mechanism of the detrimental effects of passive smoking on childhood health, however, is poorly described. The purpose of this study was therefore to examine the effect of passive smoking on total antioxidant status (TAS), total oxidant status (TOS), and paraoxonase-1 in children compared with healthy non-passive smokers. METHODS: This study included 40 children and adolescents passively exposed to cigarette smoke (as verified on urine cotinines) and 40 age- and gender-matched healthy controls not regularly exposed to cigarette smoke. TAS, TOS, and paraoxonase-1 were all measured, and the oxidative stress index (OSI) calculated for each child to determine the degree of oxidative stress. RESULTS: Age and gender distribution were not statistically different between the two groups (P = 0.619 and 0.712, respectively). Urine cotinine/creatinine was significantly higher in the passive smoking group (127.89 ± 57.14 ng/mL) compared with the controls (5.05 ± 16.66 ng/mL; P < 0.001). TAS was not different between the two groups (P = 0.767), but TOS and OSI were significantly higher for the passive smoke-exposed children (P < 0.001), and serum paraoxonase-1 was significantly lower than in the controls (P = 0.047). CONCLUSIONS: Secondhand smoke exposure is associated with increased oxidative stress and decreased paraoxonase-1 without any change in antioxidant status.

Cathelicidin (LL-37) and human ß2-defensin levels of children with post-infectious bronchiolitis obliterans.

INTRODUCTION: The antimicrobial peptides (AMPs) human ß-defensins and cathelicidin (LL-37) are key factors in innate and adaptive immune responses of the respiratory tract and play an important role in many respiratory diseases. No data are available in the literature about the levels of these AMPs in paediatric patients with post-infectious bronchiolitis obliterans (BO). This study aimed to determine human ß-defensin 2 (hBD2) and LL-37 levels and compare between post-infectious BO patients and the control group. METHOD: The patients diagnosed with post-infectious BO between September 2012 and 2013 and age- and-gender matched healthy controls were enrolled in this multi-center study. Serum hBD2 and LL37 levels were determined with the enzyme-linked immunosorbent assay method. RESULTS: Sixty-three post-infectious BO patients and 65 healthy children (median age 73 ± 55 and 78.74 ± 36.32 months, respectively) were enrolled in the study. The mean of hBD2 levels in patients and the control group were 1.06 ± 0.24 and 0.67 ± 0.72 ng/mL, respectively (P < 0.001). The mean of LL-37 levels in patients and the control group were 72.13 ± 29.06 and 50.10 ± 21.98 ng/mL, respectively (P < 0.001). No correlation was found between these AMPs levels and chronological age, age at the time of diagnosis, gender, Z-scores of weight and length, hospitalization numbers, the disease history before diagnosis and 25-OH D vitamin levels. CONCLUSION: This is the first study to demonstrate the higher levels of serum hBD2 and LL-37 levels in paediatric post-infectious BO patients. These AMPs may have important roles in the immune systems and pathogenesis of these patients.

Oxidative Stress Status in Childhood Obesity: A Potential Risk Predictor.

BACKGROUND Childhood obesity characterized by excessive fat in the body is one of the most serious health problems worldwide due to the social, medical, and physiological complications. Obesity and associated diseases are triggering factors for oxidative stress and inflammation. The aim of this study was to explore the possible association between childhood obesity and inflammatory and oxidative status. MATERIAL AND METHODS Thirty-seven obese children and 37 healthy controls selected from among children admitted to BLIND University Paediatrics Department were included in the study. Anthropometric measurements were performed using standard methods. Glucose, lipid parameters, CRP, insulin, total oxidant status (TOS), total anti-oxidant status (TAS) levels, and total thiol levels (TTL) were measured in serum. HOMA index (HOMA-IR) were calculated. The differences between the groups were evaluated statistically using the Mann-Whitney U test. RESULTS Body mass index was significantly higher in the obese group (median: 28.31(p<0.001). Glucose metabolism, insulin, and HOMA-IR levels were significantly higher in the obese group (both p<0.001). Total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels were significantly higher in the obese group (p<0.001). TAS (med: 2.5 µmol Trolox eq/L (1.7-3.3)) and TOS (med: 49.1 µmol H2O2 eq/L (34.5-78.8)) levels and TTL (med: 0.22 mmol/L (0.16-0.26)) were significantly higher in the obese group (p=0.001). CRP levels showed positive correlation with TOS and negative correlation with TTL levels (p=0.005, r=0.473; p=0.01, r=-0.417; respectively). TTL levels exhibited negative correlation with TOS levels (p=0.03, r=-0.347). CONCLUSIONS In conclusion, obese children were exposed to more oxidative burden than children with normal weight. Increased systemic oxidative stress induced by childhood obesity can cause development of obesity-related complications and diseases. Widely focussed studies are required on the use of oxidative parameters as early prognostic parameters in detection of obesity-related complications.

Renal tubular function and urinary N-acetyl-ß-d-glucosaminidase and kidney injury molecule-1 levels in asthmatic children.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways which results in chronic hypoxia. Chronic hypoxia and inflammation can affect renal tubular function. OBJECTIVES: The aim of this study was to investigate renal tubular function and early kidney injury molecules such as urinary N-acetyl-betaglucosaminidase (NAG) and kidney injury molecule-1 (KIM-1) excretion in children with asthma. METHODS: Enrolled in the study were 73 children diagnosed with asthma and 65 healthy age- and gender-matched control subjects. Urine pH, sodium, phosphorus, potassium, microalbumin, creatinine, NAG, KIM-1, and serum creatinine, sodium, phosphorus were evaluated. The diagnosis of asthma and classification of mild or moderate were done according to the Global Initiative for Asthma guidelines. RESULTS: Serum sodium, phosphorus, creatinine, and urinary microalbumin were within normal levels in the both groups. Urinary pH, sodium, potassium, phosphorus, microalbumin, and KIM-1 excretions were similar between the control and study groups. Tubular phosphorus reabsorption was within normal limits in two groups. Urine NAG was elevated in the study group (P = 0.001). Urinary KIM-1 and NAG levels were positively correlated (r = 0.837; P = 0.001). When children with mild and moderate asthma were compared, all of the parameters were similar (P >0.05). CONCLUSIONS: This study showed that chronic asthma can lead to subtle renal impacts. We suggest that in children with asthma, urinary NAG level is a more valuable parameter to show degree of renal tubular injury than markers such as microalbumin and KIM-1. Chronic hypoxy and inflammation probably contributes to these subclinical renal effects.

The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis.

Polymorphisms in the vitamin D receptor (VDR) gene have recently been reported to be associated with urinary calculi in pediatric and adult cases, but no studies have looked at the youngest period of life. The purpose of this study was to investigate the role of VDR gene polymorphisms in infantile urolithiasis in a Turkish population. We compared a study group of 104 infants (55 girls and 49 boys, mean age 6.94 ± 3.81 months) with a control group of 96 infants (51 girls and 45 boys, mean age 7.51 ± 3.23) to evaluate their demographics and metabolic risk factors. PCR-based restriction analysis of the polymorphisms on the VDR gene (BsmI and TaqI) showed statistically significant differences between study and control groups (p = 0.001 and 0.043, respectively). In addition, the prevalence of the BsmI genotype was significantly different between the hypercalciuric and normocalciuric stone formers (p = 0.007). Allelic frequencies were similar between the urolithiasis and control groups (p > 0.05). The B allele of BsmI and the A allele of ApaI were more prevalent in the hypercalciuric stone formers than in the normocalciuric stone formers (p = 0.018 vs.0.036, respectively). These results suggest that the BsmI and TaqI VDR genotypes could be candidate genes leading to infantile urolithiasis.

The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche.

BACKGROUND: Bisphenol A (BPA) is known as an endocrine disruptor and it is supposed to have a role on the development of central precocious puberty (CPP). Kisspeptin, a hypothalamic peptide, is a neuromodulator of gonadotropin releasing hormone and it has an important role on regulation of the onset of puberty. The BPA levels in girls with CPP and premature thelarche (PT) and its relation with kisspeptin levels were investigated. METHODS: Twenty-eight girls with CPP, 28 girls with PT and 22 prepubertal girls as a control group were enrolled to the study. Urinary BPA and serum kisspeptin levels were compared in the groups. Bivariate correlations were performed to evaluate the relations of BPA with kisspeptin and estradiol. RESULTS: There was no statistical difference between groups regarding BPA levels. Serum kisspeptin levels were higher in CPP group than controls [306.56 (interquartile range (IQR), 175.63-504.66) vs. 157.62 (IQR, 55.61-285.00) p: 0.008]. There were no correlations between BPA and kisspeptin levels (r: 0.088, p: 0.391) and between BPA and estradiol (r: -0.171, p: 0.144). CONCLUSIONS: The BPA levels did not differentiate between groups and it seems that the exposed amount of BPA in daily life did not affect kisspeptin levels in girls with CPP and PT.

Evaluation of 563 children with chronic cough accompanied by a new clinical algorithm.

BACKGROUND: This study aims to evaluate the children with chronic cough and to analyze their etiological factors according to the age groups. METHOD: Five hundred sixty-three children with chronic cough were included. The last diagnosis were established and were also emphasized according to the age groups. RESULTS: The mean age was 5.4 ± 3.8 years (2-months-17-years) and 52 % of them were male. The most common final diagnosis from all the participants were: asthma (24.9 %), asthma-like symptoms (19 %), protracted bacterial bronchitis (PBB) (11.9 %), and upper airway cough syndrome (9.1 %). However, psychogenic cough was the second most common diagnosis in the subjects over 6 years of age. CONCLUSION: Asthma and asthma-like symptoms were the most common diagnosis in children. Different age groups in children may have a different order of frequencies. Psychogenic cough should be thought of in the common causes especially in older children.

DNA damage and oxidative status in PFAPA syndrome.

OBJECTIVE: PFAPA syndrome is a clinical entity of unknown etiology which presents with periodic episodes of fever, aphthous stomatitis, tonsillitis or pharyngitis, and cervical adenitis. In this study we investigated DNA damage and the oxidative stress parameters in patients diagnosed with PFAPA, to elucidate the underlying pathophysiological mechanism of this syndrome. METHODS: Thirty-one patients diagnosed with PFAPA (Group 1), 22 patients diagnosed with normal tonsillitis or pharyngitis (Group 2), and 20 healthy volunteers (Group 3) were included in our study. Heparinized peripheral blood samples were drawn from all patients and volunteers. DNA damage was assessed by single cell alkaline electrophoresis assay in peripheral mononuclear leukocytes. Plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined by using a novel automated measurement method, and oxidative stress index (OSI) was calculated. RESULTS: DNA damage in the mononuclear leukocytes of Group 1 was significantly higher than that of Group 2 and Group 3. The oxidative stress parameters revealed that the TOS and OSI values of Group 1 were significantly higher than those of Group 2 and Group 3. TAS values of Group 1 were significantly lower than those of Group 2 and Group 3. Correlation analysis of Group 1 demonstrated a significant correlation between TOS, one of the oxidative stress parameters, and DNA damage. Correlations between DNA damage and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were also significant. CONCLUSION: Our study indicated that both the inflammatory and the oxidative stress parameters were significantly increased in patients with PFAPA syndrome, accompanied by a significant positive correlation between DNA damage and oxidative stress.

A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.

Relationship Between Functional Exercise Capacity and Lung Functions in Obese Chidren.

OBJECTIVE: Cardiovascular, respiratory and musculoskeletal system disorders which may affect the functional exercise capacity are common in obese patients. We aimed to investigate the functional exercise capacity and its relationship with functional pulmonary capacity in obese children. METHODS: A total of 74 obese and 36 healthy children as a control group were enrolled in the study. Pulmonary functions and functional exercise capacity were measured by spirometry and six-minute walk test (6 MWT), respectively. RESULTS: The distances covered during the 6 MWT in obese and control groups were 570.9 ± 67.5 and 607.8 ± 72.5 meters, respectively (p=0.010). In spirometric pulmonary function tests (PFTs), forced expiratory volume in 1 sec (FEV1) and forced mid-expiratory flows (25-75) were lower in the obese group (p=0.048 and p=0.047, respectively), whereas forced vital capacity (FVC), the FEV1/FVC ratio and peak expiratory flow were not statistically different between the obese and control groups. Multiple regression analysis revealed that among all parameters of anthropometric measures and PFTs, only body mass index standard deviation score (BMI-SDS) was the independent factor influencing 6 MWT. CONCLUSION: Functional exercise and lung capacities of obese children were diminished as compared to those of non-obese children. The most important factor influencing functional exercise capacity was BMI-SDS.

Vitamin D-containing supplements for children between 1-3 years of age: are they essential for bone health?

OBJECTIVE: We aim to evaluate how vitamin D-containing supplements affect the vitamin D status of children 1-3 years old and to assess the variation of the vitamin D concentrations across different seasons. METHODS-MATERIAL: This retrospective study included a review of medical reports of 1035 patients (aged 1-3 years) who presented to our hospital between October 2011 and October 2013. The children were divided into 3 groups: Group 1: those supplemented with vitamin D3 (400 IU/day), Group 2: those supplemented with multivitamins, which included 200-400 IU/day of vitamin D2 or D3, and Group 3, the controls: those not supplemented with vitamin D. The groups were compared as to their biochemical findings and variation of vitamin D status with over four seasons. RESULTS: Gender distribution was not statistically different between the three groups (p=0.38). The children who had taken vitamin D-containing supplements had significantly higher vitamin D levels compared with the children who were given no vitamin D supplementation (p<0.001). Children with no vitamin D supplementation had significantly lower calcium and phosphorus levels compared with Groups 1 and 2. Vitamin D levels were affected by vitamin D supplementation (f=16.125, p<0.001) but not by season (f=0.699, p=0.650). CONCLUSION: The children aged 1-3 years who did not receive vitamin D-containing supplements had insufficient vitamin D and low levels of calcium and phosphorus. Vitamin D levels were affected by vitamin D supplementation but not by season.

Determination of early urinary renal injury markers in obese children.

BACKGROUND: Obesity is an important health issue, the prevalence of which is increasing in childhood. The aim of this study was to examine urinary renal injury markers in order to determine the renal effect of obesity and its comorbidities in a pediatric population. METHODS: Eighty-four obese children and 64 healthy control subjects were enrolled in the study. We checked their urine using N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and microalbumin as renal injury markers. Associations of renal damage markers with hypertension, an impaired glucose tolerance test, and insulin resistance were assessed. RESULTS: Obese individuals had higher urinary NAG and KIM-1 values compared to those of healthy controls (p = 0.027, p = 0.026). There was no difference in urinary NGAL between obese and lean subjects (p = 0.885). Urinary renal injury markers were not statistically different in the obese group when checked for impaired glucose tolerance, insulin resistance, and hypertension (p > 0.05). CONCLUSIONS: This study shows that urinary NAG and KIM-1 could be used as a screening method for detection of early renal damage in obese children.