Differences in Bone Metabolism between Children with Prader-Willi Syndrome during Growth Hormone Treatment and Healthy Subjects: A Pilot Study.

Despite therapy with growth hormone (GH) in children with Prader-Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children with PWS undergoing GH therapy and a low-energy dietary intervention. Twenty-four children with PWS and 30 healthy children of the same age were included. Serum concentrations of bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), periostin, osteopontin, osteoprotegerin (OPG), sclerostin, C-terminal telopeptide of type I collagen (CTX-I), and insulin-like growth factor-I (IGF-I) were determined using immunoenzymatic methods. OC levels and the OC/CTX-I ratios were lower in children with PWS than in healthy children (p = 0.011, p = 0.006, respectively). Glu-OC concentrations were lower (p = 0.002), but Gla-OC and periostin concentrations were higher in patients with PWS compared with the controls (p = 0.005, p < 0.001, respectively). The relationships between IGF-I and OC (p = 0.013), Gla-OC (p = 0.042), and the OC/CTX-I ratio (p = 0.017) were significant after adjusting for age in children with PWS. Bone turnover disorders in children with PWS may result from impaired bone formation due to the lower concentrations of OC and the OC/CTX-I ratio. The altered profile of OC forms with elevated periostin concentrations may indicate more intensive carboxylation processes of VKDPs in these patients. The detailed relationships between the GH/IGF-I axis and bone metabolism markers, particularly VKDPs, in children with PWS requires further research.

Are Omentin Rs2274907 and Vaspin Rs2236242 Gene Polymorphisms Related to Body Composition, Lipid Profile and Other Adipokines in Prepubertal Healthy Children?

Purpose/Aim: So far no research concerning the omentin-1 (ITLN1) rs2274907 and vaspin (SERPINA12) rs2236242 polymorphisms has been carried out in a healthy pediatric population. We analyzed associations of these polymorphisms with anthropometric parameters, lipid profile, as well as adiponectin, leptin and soluble leptin receptor (sOB-R) levels in prepubertal healthy children, to search for their possible role in the risk of obesity and obesity-related disorders.Materials and Methods: Frequencies of these polymorphisms were analyzed by the restriction fragment length polymorphism in 89 normal-weight children. The body composition was measured by dual-energy X-ray absorptiometry. Serum levels of adipokines were measured using ELISA methods.Results: We observed differences in values of HDL-cholesterol (p = 0.002) and triglycerides (p = 0.039) in children carrying different genotypes of the ITLN1 rs2274907 polymorphism. In children carrying different genotypes of the SERPINA12 rs2236242 polymorphism differences in BMI (p =0.025) and BMI Z-score (p = 0.01) values were found. Significant relations between anthropometric parameters and levels of HDL-cholesterol and triglycerides were associated with minor alleles of the studied polymorphisms. In addition, leptin/sOB-R ratio was related to HDL-cholesterol (p = 0.004) and triglycerides (p = 0.03) levels in children carrying minor allele of the SERPINA12 rs2236242 SNP.Conclusions: We suggest that both ITLN1 rs2274907 and SERPINA12 rs2236242 polymorphisms influence body composition and lipid profile in prepubertal healthy children. Relations between anthropometric parameters, lipid and adipokine levels may be associated with minor alleles of the studied polymorphisms. The possible role of these polymorphisms in the modulation of the risk of obesity and obesity-related disorders in the later life might be considered.

The effect of weight loss on body composition, serum bone markers, and adipokines in prepubertal obese children after 1-year intervention.

Purpose/Aim: The influence of weight loss on bone turnover and bone quality in childhood remains controversial, but it may implicate interactions between adiposity and bone metabolism. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. MATERIALS AND METHODS: We determined serum leptin, soluble leptin receptor, adiponectin, bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), sclerostin, body composition, and bone mineral density (BMD) in 40 obese prepubertal children before and after therapy. The control group, matched for sex and age, consisted of 40 non-obese children. RESULTS: We found that values of the total body less head-bone mineral content (TBLH-BMC) and TBLH-BMD were significantly increased, but TBLH-BMD Z-score was decreased by 25% (p = 0.002) in obese children with weight loss after therapy. We observed increases of CTX-I to OC ratio (p = 0.009), and Gla-OC concentrations (p = 0.049). Changes in TBLH-BMD Z-score in patients were positively correlated with changes in BMI Z-score (p = 0.001), percentage of fat mass (p = 0.004), and BALP activity (p = 0.01). Changes in BALP activity were negatively correlated (p < 0.001) with changes in adiponectin concentrations, while changes in sclerostin levels were positively correlated (p = 0.001) with leptin changes. CONCLUSIONS: We suggest that alterations in adipokines metabolism were associated with a lower rate of bone mineral accrual as a result of decreased bone formation rather than increased bone resorption. The lower rate of bone mass accrual in weight losing children may be an effect of reduced BALP levels related to increase in adiponectin levels.

The levels of bone alkaline phosphatase (BALP) and soluble epidermal growth factor receptor-2 (ECD/HER-2) in pediatric patients with osteosarcoma during clinical treatment.

OBJECTIVE: Aim: The aim of this study was to assess the usefulness of bone-specific alkaline phosphatase (BALP) and the extracelluar domain of human epidermal growth factor receptor 2 (ECD/HER-2) measurements in pediatric patients with osteosarcoma as prospective prognostic and predictive markers for monitoring the treatment and early detection of disease recurrence. PATIENTS AND METHODS: Material and methods: We studied 22 patients (5 girls, 17 boys) aged 7-20 years with osteosarcoma (OS) treated at the Institute of Mother and Child in Warsaw. All the patients were evaluated for the serum levels of BALP and ECD/HER-2 before treatment, during pre- and postoperative chemotherapy and after the completion of treatment. Healthy children (n=22) were the reference group. The levels of BALP and ECD/HER-2 were measured using immunoenzymatic methods. RESULTS: Results: The values of BALP and ECD/HER-2 proteins were higher (p<0.01; p<0.05, respectively) in patients with osteosarcoma at the time of diagnosis compared with the control group. The values of both markers significantly decreased during chemotherapy in most patients with remission. In contrast to ECD/HER-2, the value of BALP after therapy was higher in patients with progression than with remission (p<0.001). CONCLUSION: Conclusions: Our results demonstrate the different pattern of BALP and ECD/HER-2 proteins during clinical treatment in patients with osteosarcoma. Higher values of BALP may characterize the progression of the disease and unfavourable prognosis. Further longitudinal studies are necessary to confirm the prognostic values of BALP and ECD/HER-2 proteins in this group of patients.

Relations between oxidized low-density lipoproteins and fat-soluble vitamin concentrations in obese children - preliminary study.

INTRODUCTION: Although lipid peroxidation products are formed during normal cell metabolism, they appear mostly in pathological conditions via producing an excess of free radicals that can react with unsaturated fatty acids, in particular low-density lipoprotein (LDL). The aim of this study was to investigate the relations between oxidized LDL (oxLDL), the fat-soluble vitamin status and the anthropometric parameters in prepubertal obese children. MATERIAL AND METHODS: Thirty-two obese (SDS-BMI >2) and 25 non-obese children (SDS-BMI <-1+1>) were included in the study. The concentration of oxLDL was determined in the serum by the ELISA assay. Vitamin A and E were measured by the high-pressure liquid chromatography method. Total cholesterol, LDL- and HDL-cholesterol, and triglyceride levels were determined by enzymatic methods. RESULTS: The concentrations of oxLDL and vitamin A were higher in obese children than in normalweight controls by about 50% (p=0.01) and 40% (p=0.001), respectively. In obese children the significant positive correlation was found between oxLDL and vitamin A concentrations (<0.05). In addition, oxLDL correlated positively with BMI values (<0.05) and the amount of fat mass (kg) (<0.02) in these patients. Concentrations of vitamins A and E correlated with the level of total cholesterol (<0.05; <0.01, respectively).Moreover, a positive correlation between vitamin E and LDL-cholesterol was observed (<0.05). CONCLUSIONS: Our preliminary study shows that oxLDL starts early during the prepubertal period and may precede atherosclerotic lesions. We suggest there is an occurrence of relationships between vitamin A and oxidized LDL in prepubertal obese children. Vitamin A and E concentrations are also associated with dyslipidemia in these patients.

ADIPOQ -11377C>G Polymorphism Increases the Risk of Adipokine Abnormalities and Child Obesity Regardless of Dietary Intake.

OBJECTIVE: The aim of the present study was to verify whether selected functional single nucleotide polymorphisms in LEP, LEPR, and ADIPOQ loci are associated with the development of obesity and serum levels of the respective adipokines in prepubertal white children with obesity. METHODS: Frequencies of -2548G>A LEP (rs7799039), Q223R (rs1137101) and K656N (rs8129183) LEPR, and -11377C>G (rs266729) and -11426A>G (rs16861194) ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism in 101 obese (standard deviation score [SDS]-body mass index [BMI] >2) and 67 normal-weight (SDS-BMI <- 1 + 1 >) children. Serum adipokine concentrations were measured using the enzyme-linked immunosorbent assay method. RESULTS: The GC/GG genotypes of -11377C>G ADIPOQ polymorphism were associated with a higher risk of obesity (P = 0.022, odds ratio 2.08 [95% confidence interval 1.11-3.90]). Individuals carrying the GG genotype had a higher leptin/total adiponectin ratio by 25% than CC homozygotes (P trend = 0.05). In the multivariate linear regression model, we found differences among particular genotypes of this polymorphism in concentrations of high molecular weight (HMW) adiponectin (P trend = 0.043) and HMW/total adiponectin ratio (P trend = 0.048), with the lowest values in GG homozygotes. Positive correlations between SDS-BMI and dietary reference intake percentage were observed in individuals homozygous for allele C (r = 0.403, P = 0.01) and CG heterozygotes (r = 0.428, P = 0.004). No significant correlations between both parameters were found in the GG homozygotes. CONCLUSIONS: Among the analyzed polymorphisms, only -11377C>G ADIPOQ single nucleotide polymorphism was associated with obesity during the prepubertal period. Adipokine abnormalities coexisting with the lack of relations between SDS-BMI and dietary intake may predict a higher risk of future obesity-related disorders in obese children carrying the GG genotype than in those with other genotypes.

[Serum concentrations of visfatin and oxidative stress markers in tobacco smoking pregnant women].

Tobacco smoking during pregnancy increases the risk of severity of oxidative stress, which can affect adipokines expression in adipose tissue. The aim of the study was to assess the effects of smoking on the level of visfatin and selected markers of oxidative stress (ox-LDL- oxidized low density lipoprotein, TOC - total oxidant capacity, TAC - total antioxidant capacity) and the association between them in pregnant women. Material and Methods: The research material was the venous blood of healthy women admitted to given birth in the Department of Obstetrics and Gynecology Institute of Mother and Child in the years 2015 - 2016. Based on an interview and determination of serum cotinine, women were divided into following groups: smoking (n=41) and non-smoking group (n=43). Concentrations of biochemical parameters were determined by enzyme immunoassay using commercial kits. Results: In serum of smoking pregnant women concentrations of visfatin, ox-LDL, and TOC were significantly higher while level of TAC was lower than observed in nonsmoking group (p<0.001). We found important association between number of cigarettes daily consumed and serum level of visfatin (r=0.43; p<0.01), ox-LDL (r=0.36; p<0.05), and TOC (r=0.39; p<0.05). Multivariate regression analysis showed a positive correlation between concentration of visfatin and level of ox-LDL as well as TOC both in the smoking women (ox- LDL: ß=0.381; TOC: ß=0.388; p<0.05), and in tobacco abstinent group (ox- LDL: ß= 0.470; TOC: ß=0.326; p<0.05). Conclusions: These results indicate that smoking during pregnancy adversely affect the oxidant/ antioxidant balance. The association between visfatin concentrations and markers of oxidative stress may suggest prooxidant tendency of this adipokine.

Body composition parameters and adipokines levels in relation to bone mineral density in patients with malignant bone tumors after treatment.

BACKGROUND: Recent data support the concept that adipokines, which are secreted by fat cells, are important modulators of bone metabolism. The aim of this study was to assess the relationships between body composition parameters, adipokines (leptin, adiponectin) and bone mineral density (BMD) in patients with malignant bone tumors after anticancer therapy. PROCEDURE: The study included 35 patients (median age 14.8 years) with diagnosed malignant bone tumors treated according to obligatory protocols. Total fat mass, lean mass, bone mineral content (BMC) and BMD measurements were performed after treatment completion by dual energy-ray absorptiometry (DXA). Serum concentrations of leptin, leptin receptor and adiponectin were determined using immunoenzymatic assays. The control group consisted of 28 healthy children (median age 14.3 years). RESULTS: Patients with bone tumor after chemotherapy had significantly higher fat mass (P < 0.01), increased ratio of fat mass/lean mass (P < 0.001), and a decrease (P < 0.001) in total body and lumbar spine BMD compared with controls. We observed higher serum leptin concentration (P < 0.01) and lower soluble leptin receptor (P < 0.001) and adiponectin (P = 0.01) in patients than in controls. The ratios of leptin/leptin receptor and leptin/adiponectin were about three-fold higher in patients compared with the control group (P = 0.001). We found a significant positive correlation between BMD and body composition and a negative correlation between BMD and adiponectin in the patients group. CONCLUSIONS: Changes in body composition parameters coexisting with disturbed adipokine levels, especially higher levels of leptin and lower levels of adiponectin, might be associated with bone status in patients treated for malignant bone tumors.

[Adipokines, body composition and bone mineral density in underweight children]. / Adipokiny, parametry skladu ciala i gestosc mineralna kosci u dzieci z niedoborem masy ciala.

UNLABELLED: One of the important factors affecting bone health is body weight. Underweight children are predisposed to disturbances in bone metabolism, which may result in osteopenia and osteoporosis in later life. AIM: The aim of the study was to assess the relationship between adipokines, bone metabolism, and anthropometric parameters in underweight prepubertal children. MATERIALS AND METHODS: The study included 60 children aged 5-10 years. Among them, there were: 30 underweight children (BMI z-score ≤-1) and 30 normal-weight children (BMI z-score <-1 + 1 >). Body composition (fat mass, lean body mass, bone mass) and bone mineral density examination were performed by densitometry. Serum concentrations of bone metabolism markers and adipokines were determined by immunoenzymatic methods. RESULTS: In underweight children we observed significantly lower fat mass (p<0.0001), lean mass (p<0.001), bone mineral content (p<0.01) and bone mineral density both the total body (p<0.01) as well as lumbar spine L2-L4 (p<0.05) compared with normal-weight children. In the group of underweight children, serum concentration of bone resorption marker (CTX) was significantly higher than in normal-weight children (2.006±0.649 vs. 1.624±0.492 ng/ml, p<0.05), with no differences in the concentrations of osteocalcin and sclerostin between studied groups. The ratio of adipokines (leptin/adiponectin) was approximately 2-fold lower in underweight than in normal-weight subjects. In underweight children we observed positive correlations between concentrations of sclerostin and bone turnover markers (OC, CTX) and between adiponectin and CTX. However, there was no correlation between fat mass and leptin concentration in this group of children. CONCLUSIONS: Low body weight in prepubertal period is related with an alteration in the adipokines profile and bone metabolism markers, resulting in a decrease in bone mineral density.

[Umbilical cord serum hepcidin levels and maternal smoking during pregnancy]. / Stezenia hepcydyny we krwi pepowinowej dzieci matek palacych tyton w przebiegu ciazy.

Anemia during pregnancy is a risk factor of disturbance in pre- and postnatal child's development. Hepcidin plays the key role in iron metabolism, as protein participating in the regulation of intestinal absorption of this element and its release from macrophages, and transport across the placenta. Maternal smoking during pregnancy can result in disturbances of iron homeostasis leading to a subclinical deficiency. The depletion of maternal iron can cause fetal hypoxia condition and decreased expression of hepcidin. The aim of the study was to evaluate the effect of smoking on the levels of hepcidin and erythropoietin (as an indicator of hypoxia) and their relationships in umbilical cord blood. The research material was the umbilical cord blood of 50 newborns born in the Department of Obstetrics and Gynecology (Institute of Mother and Child in Warsaw) in the years 2013-2014. Based on an interview and determination of cotinine in the blood of mothers, newborns were divided into following groups: children of smoking mothers (n=20) and children of tobacco abstinent mothers (n=30). Hepcidin and erythropoietin concentrations were determined by enzyme immunoassay using commercial kits (DRG, Germany). It has been shown that hepcidin concentrations were significantly lower in children of smoking mothers than in the group of tobacco abstinent (37.5 ng/mL vs 45.1 ng/mL, p<0.001). However, the level of erythropoietin was higher in children of smoking mothers than in children of non-smoking women (p<0.001). A negative correlation between the levels of hepcidin and erythropoietin (r = -0.41, p<0.05) and number of smoked cigarettes (r = -0.43, p<0.05) was observed. These results indicate that smoking during pregnancy significantly affects hepcidin levels in children born at term. Decrease of hepcidin concentration coexisting with high level of erythropoletin in umbilical cord blood in children of smoking pregnant women may be the cause of subclinical deficiency of iron in the newborn.

[Assessment of anthropometric parameters and serum leptin and fetuin-A levels in children and adolescents with osteosarcoma after anticancer treatment]. / Ocena parametrów antropometrycznych oraz stezen leptyny i fetuiny-A u dzieci i mlodziezy po zakonczeniu leczenia miesaka kosciopochodnego.

UNLABELLED: Cancer and the use of a comprehensive anti-cancer treatment are unfavorable factors, which have a significant impact on bone mass accumulation, bone mineralization and consequently the occurrence of osteoporosis. Bone turnover is regulated by complex mechanisms, among which an important role play OPG/RANK/RANKL signaling pathway, adipokines, and fetuin-A. The aim of the study was to evaluate bone mineral density and concentrations of leptin and fetuin-A in patients with osteosarcoma after anti-cancer treatment. MATERIALS AND METHODS: The study included 50 children and adolescents aged 10-21 years. The study group consisted of 25 patients with osteosarcoma and 25 healthy counterparts as a control group. The examination was conducted 2 months after the last course of postoperative chemotherapy and included densitometric measurements: bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass and biochemical measurements: serum concentrations of calcium, magnesium, phosphate, 25-hydroksyvitamin D, alkaline phosphatase, leptin and fetuin-A. Concentrations of leptin and fetuin-A were determined by immunoenzymatic methods. RESULTS: In patients with osteosarcoma after anti-cancer treatment, we observed significantly reduced bone mineral content, bone mineral density and lean body mass compared with the healthy children (p < 0.05, p < 0.01, p < 0.05, respectively). Mean values of z-score of the whole body BMD and z-score of the lumbar BMD L1-L4 were significantly lower in patients than in the controls (p < 0.001). The serum concentrations of phosphate, magnesium, and alkaline phosphatase in both studied groups were similar, while calcium was significantly lower (p < 0.05) in patients than in the healthy children. The concentration of 25-hydroxyvitamin D was about two-fold lower, while leptin approximately 2.5-fold higher in patients than in the controls. The mean value of fetuin-A was similar in both studied groups. Statistically significant positive correlations between body composition parameters and the values of BMD, as well as between anthropometric parameters and leptin and fetuin-A were observed. CONCLUSION: The deficit in bone mass observed in patients with malignant bone tumors after anti-cancer treatment might be the result of decreased serum calcium and vitamin D concentrations. The observed correlation between anthropometric and biochemical parameters may indicate the link between bone and adipose tissue metabolism.

Effect of tobacco smoking on the maternal and fetal adipokine axis in relation to newborn birth weight and length.

We examined the effect of tobacco smoking on the concentrations of leptin, soluble leptin receptor (sOB-R), total adiponectin, and free leptin index (FLI) in the serum of maternal-cord pairs. We also investigated the correlations between these biochemical parameters and newborn birth weight and length. The study included eighty-five healthy pregnant women, who were divided into smoking and tobacco- abstinent groups according to serum cotinine concentrations. We found that maternal and fetal leptin, sOB-R concentrations, and free leptin index were similar in smoking and tobacco abstinent groups. We observed significant negative relationship between the reported number of cigarettes smoked daily during pregnancy and cord blood leptin (r=-0.37; p<0.05). In the group of smoking women, total serum adiponectin concentrations were significantly lower than in the tobacco abstinent group in mothers as well as in cord blood (p<0.05). A significant negative association between the number of cigarettes smoked per day and total adiponectin concentration in maternal as well as newborn serum was observed (r=-0.38; p<0.05). Umbilical serum leptin, sOB-R, and FLI levels were significantly lower and adiponectin higher compared with maternal concentrations at birth (p<0.05). Mean birth weight and body length of the smoking mothers' infants were significantly lower (p<0.001; p=0.015, respectively) compared with the abstinent group, and negatively correlated with the daily number of cigarettes consumed (birth weight r=-0.39; p<0.05; birth length r=-0.37; p<0.05). Cord blood values of leptin, FLI and adiponectin were significantly correlated with newborn birth weight. We also observed a positive relationship between cord blood adiponectin levels and the birth body length in the two studied groups (r=0.49; p<0.002). Tobacco smoking during pregnancy decreases maternal and fetal serum adiponectin levels but does not have a significant effect on blood leptin concentrations. The direct association between the cord blood values of these adipokines and birth weight and length suggest that rather fetal (not maternal) adiponectin and leptin concentrations may be involved in fetal development during pregnancy.

Comparative Analysis of Myokines and Bone Metabolism Markers in Prepubertal Vegetarian and Omnivorous Children.

The role of bone and muscle as endocrine organs may be important contributing factors for children's growth and development. Myokines, secreted by muscle cells, play a role in regulating bone metabolism, either directly or indirectly. Conversely, markers of bone metabolism, reflecting the balance between bone formation and bone resorption, can also influence myokine secretion. This study investigated a panel of serum myokines and their relationships with bone metabolism markers in children following vegetarian and omnivorous diets. A cohort of sixty-eight healthy prepubertal children, comprising 44 vegetarians and 24 omnivores, participated in this study. Anthropometric measurements, dietary assessments, and biochemical analyses were conducted. To evaluate the serum concentrations of bone markers and myokines, an enzyme-linked immunosorbent assay (ELISA) was used. The studied children did not differ regarding their serum myokine levels, except for a higher concentration of decorin in the vegetarian group (p = 0.020). The vegetarians demonstrated distinct pattern of bone metabolism markers compared to the omnivores, with lower levels of N-terminal propeptide of type I procollagen (P1NP) (p = 0.001) and elevated levels of C-terminal telopeptide of type I collagen (CTX-I) (p = 0.018). Consequently, the P1NP/CTX-I ratio was significantly decreased in the vegetarians. The children following a vegetarian diet showed impaired bone metabolism with reduced bone formation and increased bone resorption. Higher levels of decorin, a myokine involved in collagen fibrillogenesis and essential for tissue structure and function, may suggest a potential compensatory mechanism contributing to maintaining bone homeostasis in vegetarians. The observed significant positive correlations between myostatin and bone metabolism markers, including P1NP and soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), suggest an interplay between muscle and bone metabolism, potentially through the RANK/RANKL/OPG signaling pathway.

Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

BACKGROUND: Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. MATERIALS AND METHODS: A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. RESULTS: Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. CONCLUSIONS: We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

[The effect of tobacco smoking on serum concentration of selected angiogenic factors and somatomedin C in pregnant women and umbilical cord blood]. / Wplyw palenia tytoniu na stezenia wybranych czynników angiogennych oraz somatomedyny C w surowicy krwi kobiet ciezarnych i krwi pepowinowej.

The objective of this study was to evaluate the effect of cigarette smoking on concentration of selected angiogenic factors (vascular endothelial growth factor VEGF, placenta growth factor PIGF) and somatomedin C (insulin-like growth factor-I) in blood of mothers and umbilical cord blood. The correlations between studied biochemical parameters and markers of estimated intensity of cigarette smoking as well as birth weight were also determined. Fifty healthy pregnant women were divided into two groups: smoking and tobacco abstinent group according to serum cotinine concentration. The current smokers were defined as those who had smoked 5 cigarettes per day for 2 years before conception and continued smoking during pregnancy. In the group of smoking mothers the mean serum concentration of cotinine was 91.6 microg/L and correlated positively with number of cigarettes daily consumed (r = 0.58, p < 0.01) as well as with time of smoking before conception (r = 0.40, p < 0.05). The mean serum concentration of PIGF in III trimester of pregnancy was significantly higher in the group of smokers than in non-smoking ones (p < 0.0001) and correlated with serum cotinine concentration (r = 0.41, p < 0.05) and number of cigarettes daily consumed (r = 0.58, p < 0.01). The concentration of serum VEGF was similar in both studied group. The mean serum level of IGF-I was significantly lower in group of smokers than in non-smokers in the I and III trimester of gestation (p < 0.01). Also in umbilical cord blood of smoking newborn the concentration of IGF-I was lower by 20% than in nonsmoking group (p < 0.05). We observed negative correlation between number of cigarettes daily consumed and serum level of IGF-I in blood of mothers as well as in blood of their children (I trimester: r = -0.43, p < 0.05; III trimester: r = -0.70, p < 0.001; umbilical cord blood: r = -0.45, p < 0.05). In both studied groups there were a positive correlation between birth weight and concentrations of IGF-I in blood of mothers and umbilical cord blood (group of smokers: mothers r = 0.43, p < 0.05, cord blood r = 0.50, p < 0.01; group of tobacco abstinent: mothers r = 0.51, p < 0.01, cord blood r = 0.41, p < 0.05). The birth weight of the smoking mothers' infants was lower by about 400 g (p < 0.01) and their birth body length by 1.5 cm (p < 0.05) and negatively correlated with number of cigarettes smoked per day (r = -0.55; p < 0.005). Our results indicate, that tobacco smoking during pregnancy increased serum PIGF levels in the final stages of gestation and has no effect on the concentration of VEGF, which may lead to an increase of trophoblast proliferation and uteroplacental dysfunction. Lower than in tobacco abstinent levels of IGF-I in serum of smoking mothers and in umbilical cord blood and their close relationship with birth weight, may suggests a direct effect of this factor on birth anthropometric parameters.

Circulating Levels of Nesfatin-1 and Spexin in Children with Prader-Willi Syndrome during Growth Hormone Treatment and Dietary Intervention.

BACKGROUND: Despite observable improvement in the treatment outcomes of patients with Prader-Willi syndrome (PWS), adequate weight control is still a clinical problem. Therefore, the aim of this study was to analyze the profiles of neuroendocrine peptides regulating appetite-mainly nesfatin-1 and spexin-in children with PWS undergoing growth hormone treatment and reduced energy intake. METHODS: Twenty-five non-obese children (aged 2-12 years) with PWS and 30 healthy children of the same age following an unrestricted age-appropriate diet were examined. Serum concentrations of nesfatin-1, spexin, leptin, leptin receptor, total adiponectin, high molecular weight adiponectin, proinsulin, insulin-like growth factor-I, and total and functional IGF-binding protein-3 concentrations were determined using immunoenzymatic methods. RESULTS: The daily energy intake in children with PWS was lower by about 30% (p < 0.001) compared with the controls. Daily protein intake was similar in both groups, but carbohydrate and fat intakes were significantly lower in the patient group than the controls (p < 0.001). Similar values for nesfatin-1 in the PWS subgroup with BMI Z-score < -0.5 and the control group, while higher values in the PWS subgroup with BMI Z-score ≥ -0.5 (p < 0.001) were found. Spexin concentrations were significantly lower in both subgroups with PWS than the controls (p < 0.001; p = 0.005). Significant differences in the lipid profile between the PWS subgroups and the controls were also observed. Nesfatin-1 and leptin were positively related with BMI (p = 0.018; p = 0.001, respectively) and BMI Z-score (p = 0.031; p = 0.027, respectively) in the whole group with PWS. Both neuropeptides also correlated positively in these patients (p = 0.042). CONCLUSIONS: Altered profiles of anorexigenic peptides-especially nesfatin-1 and spexin-in non-obese children with Prader-Willi syndrome during growth hormone treatment and reduced energy intake were found. These differences may play a role in the etiology of metabolic disorders in Prader-Willi syndrome despite the applied therapy.

Assessment of Oxidant and Antioxidant Status in Prepubertal Children following Vegetarian and Omnivorous Diets.

Oxidant-antioxidant balance is crucial for maintaining one's health, and the diet is possibly one of the most important factors affecting this balance. Therefore, the aim of this study was to determine the oxidant-antioxidant balance in children on a lacto-ovo-vegetarian diet. The study was conducted between January 2020 and December 2021. The concentrations of total oxidant capacity (TOC), total antioxidant capacity (TAC), reduced (GSH), and oxidized (GSSG) glutathione, as well as C-reactive protein (CRP) and calprotectin were measured in serum samples of 72 healthy prepubertal children (32 vegetarians and 40 omnivores). The oxidative stress index (OSI) and the GSH/GSSG ratio (R-index) were calculated. Children on a vegetarian diet had significantly lower median values of TOC, GSH, and GSSG, and higher TAC compared with the omnivores. OSI was significantly lower in vegetarians, while R-index, as well as median values of CRP and calprotectin did not differ between both groups of children. Significant negative correlations were observed between TOC and TAC levels in the whole group of children and in vegetarians. GSH and GSSG levels correlated positively in the groups of vegetarians, omnivores, and in all the children. There were significant positive correlations between TOC and GSH, as well as GSSG levels in all the studied groups of children. Our study results suggest that the vegetarian model of nutrition allows to maintain the oxidant-antioxidant balance in the serum of prepubertal children.

Antioxidant Defense Expressed as Glutathione Status and Keap1-Nrf2 System Action in Relation to Anthropometric Parameters and Body Composition in Young Women with Polycystic Ovary Syndrome.

Metabolic disorders present in women with polycystic ovary syndrome (PCOS) and the associated risk of obesity may result in increased oxidative stress and reproductive failure. Therefore, we evaluated the concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GPx), and reductase (GR), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein1 (Keap1) in the serum of 56 women with PCOS divided according to the visceral to subcutaneous fat surface ratio (VAT/SAT) and waist-to-hip ratio (WHR) values. Antioxidant parameter levels were measured by competitive inhibition enzyme immunoassay technique. As the VAT/SAT ratio and WHR increased, we observed significantly higher concentrations of GSSG and Keap1 protein and a lower value of the GSSG/GSH ratio (R-index), which is considered an index of cellular redox (p < 0.05). Negative correlations were found between the R-index and body weight, BMI, WHR, subcutaneous and visceral fat surface and the VAT/SAT ratio, and total body fat; positive links were found with fat free mass and total body water. Opposite associations were noted between GSSG level and the aforementioned body composition parameters. Oxidative stress characterized by a depleted reduced-to-oxidized glutathione index is associated with anthropometric and body composition parameters in women with PCOS. In particular, abdominal obesity expressed by the VAT/SAT ratio and/or WHR seems to have a negative impact on glutathione status, which may lead to a disruption of many biological cell processes. The observed negative association of Keap1 with R-index suggests that the elevated oxidative changes dependent on the VAT/SAT ratio may lead to Nrf2 activation to promote antioxidant enzyme expression. Although the GSH/GSSG index as well as the VAT/SAT ratio appear to be good indicators of oxidative status, studies on a larger group of patients should continue to confirm these links among women with PCOS.

Dietary Intake and Circulating Amino Acid Concentrations in Relation with Bone Metabolism Markers in Children Following Vegetarian and Omnivorous Diets.

Scientific studies reported that most vegetarians meet the total protein requirements; however, little is known about their amino acid intakes. We aimed to assess dietary intake and serum amino acid levels in relation to bone metabolism markers in prepubertal children on vegetarian and traditional diets. Data from 51 vegetarian and 25 omnivorous children aged 4-9 years were analyzed. Dietary intake of macro- and micronutrients were assessed using the nutritional program Dieta 5®. Serum amino acid analysis was performed using high-pressure liquid chromatography technique, 25-hydroxyvitamin D and parathormone-electrochemiluminescent immunoassay, and bone metabolism markers, albumin, and prealbumin levels using enzyme-linked immunosorbent assay. Vegetarian children had a significantly lower intake of protein and amino acids with median differences of about 30-50% compared to omnivores. Concentrations of four amino acids (valine, lysine, leucine, isoleucine) in serum varied significantly by diet groups and were lower by 10-15% in vegetarians than meat-eaters. Vegetarian children also had lower (p < 0.001) serum albumin levels compared to omnivores. Among bone markers, they had higher (p < 0.05) levels of C-terminal telopeptide of collagen type I (CTX-I) than omnivores. Correlation patterns between amino acids and bone metabolism markers differed in the vegetarian and omnivore groups. Out of bone markers, especially osteoprotegerin was positively correlated with several amino acids, such as tryptophan, alanine, aspartate, glutamine, and serine, and ornithine in vegetarians. Vegetarian children consumed apparently sufficient but lower protein and amino acids compared to omnivores. In circulation these differences were less marked than in the diet. Significantly lower amino acid intake and serum levels of valine, lysine, leucine, and isoleucine as well as the observed correlations between serum amino acids and biochemical bone marker levels indicated the relations between diet, protein quality, and bone metabolism.

Associations between Oxidant/Antioxidant Status and Circulating Adipokines in Non-Obese Children with Prader-Willi Syndrome.

Oxidative stress is implicated in the pathophysiology of Prader-Willi syndrome (PWS), but there are no data on these disorders in non-obese children with PWS. Therefore, the presented study examined total oxidant capacity (TOC), total antioxidant capacity (TAC), the oxidative stress index (OSI), and adipokine levels in 22 non-obese children with PWS during dietary intervention and growth hormone treatment compared with 25 non-obese healthy children. Serum concentrations of TOC, TAC, nesfatin-1, leptin, hepcidin, ferroportin, and ferritin were determined using immunoenzymatic methods. We found that TOC concentrations were higher by 50% (p = 0.006) in patients with PWS than in healthy children, but no significant differences in TAC concentrations were observed between these groups. The OSI was higher in children with PWS than in the controls (p = 0.002). We found positive associations between TOC values and the percentage of the Estimated Energy Requirement, body mass index (BMI) Z-score, percentage of fat mass, and leptin, nesfatin-1, and hepcidin concentrations in patients with PWS. A positive association was also found between the OSI and nesfatin-1 levels. These observations suggest that higher daily energy intake and weight gain may be accompanied by an increasing prooxidant state in these patients. Adipokines such as leptin, nesfatin-1, or hepcidin may also play a role in the prooxidant state in non-obese children with PWS.