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.

Oxidative and Antioxidative Status Expressed as OSI Index and GSH/GSSG Ratio in Children with Bone Tumors after Anticancer Therapy Completion.

Aims. There are no data on the redox status of children with bone tumors in complete disease remission. Therefore, the presented study examined the reduced/oxidized glutathione (GSH/GSSG) ratio, total oxidant capacity (TOC) and total antioxidant capacity (TAC) values as well as the oxidative stress index (OSI) for assessing alterations in the oxidant/antioxidant balance in 35 children with osteosarcoma or Ewing's sarcoma after anticancer therapy completion (median 14 months) compared with a control group. Methods. GSH, GSSG, TOC, TAC concentrations and bone alkaline phosphatase (BALP) activity were evaluated by immunoenzymatic (ELISA) and enzymatic methods. Results. We found no differences in serum BALP activity between all survivors with bone tumors and the control group. Patients with osteosarcoma after anticancer therapy completion had significantly higher values of TAC, GSH and the GSH/GSSG ratio as well as GSSG than healthy subjects. In patients with Ewing's sarcoma, we found significantly higher values of TOC concentration compared with healthy children. In addition, survivors with Ewing's sarcoma had higher TOC concentrations and OSI index values (p < 0.01), but a lower GSH/GSSG ratio (p < 0.05) than survivors with osteosarcoma. A positive correlation between TOC and the post-therapy period was observed in survivors. Conclusions. We found that in survivors with bone tumors, a disturbed balance between prooxidants and antioxidants persists after the completion of anticancer treatment. Moreover, an increased TOC value together with the post-therapy period may suggest increasing oxidative processes in survivors with bone tumors after treatment. Further observations will allow assessment of the relationship between the oxidant/antioxidant status and the predisposition of survivors to bone neoplastic disease recurrence.

Influence of Oxidative Stress Generated by Smoking during Pregnancy on Glutathione Status in Mother-Newborn Pairs.

Glutathione plays a key role in maintaining a physiological balance between prooxidants and antioxidants in the human body. Therefore, we examined the influence of maternal smoking as a source of oxidative stress measured by total oxidant capacity (TOC) on reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GPx-3), and reductase (GR) amount in maternal and umbilical cord blood in 110 (45 smoking and 65 non-smoking) mother-newborn pairs. Concentrations of glutathione status markers and TOC were evaluated by competitive inhibition enzyme immunoassay technique. Plasma TOC levels were significantly higher and the GSH/GSSG ratio, which is considered an index of the cell's redox status, were significantly lower in smoking women and their offspring than in non-smoking pairs. Decreased GR levels were found in smoking mothers and their newborns compared with similar non-smoking groups. Although plasma GPx-3 concentrations were similar in both maternal groups, in the cord blood of newborns exposed to tobacco smoke in utero they were reduced compared with the levels observed in children of tobacco abstinent mothers. Oxidative stress generated by tobacco smoke impairs glutathione homeostasis in both the mother and the newborn. The severity of oxidative processes in the mother co-existing with the reduced potential of antioxidant systems may have a negative effect on the oxidative-antioxidant balance in the newborn.

Associations Between Antioxidant Vitamin Status, Dietary Intake, and Retinol-binding Protein 4 Levels in Prepubertal Obese Children After 3-month Weight Loss Therapy

Objective: Adiposity is associated with increased oxidative stress, leading to changed fat-soluble vitamin concentrations. The aim of this study was to determine whether weight loss alters fat-soluble vitamin status and whether these alterations are associated with dietary intake, anthropometric parameters and adipokines in obese children. Methods: Vitamin A and E concentrations were measured using high-pressure liquid chromatography in 60 obese children before and after weight loss therapy. Retinol-binding protein 4 (RBP4), leptin, soluble leptin receptor (sOB-R), and high molecular weight adiponectin concentrations were determined by immunoenzymatic assays. Results: The intake of vitamin E was lower in obese children with weight loss after therapy (p=0.038). In this group, an increase was found in the vitamin A/lipids (p=0.022) and the vitamin E/lipids (p=0.008) ratios but due to the reduction in triglyceride levels. In the obese group, changes in vitamin E level were positively correlated with changes in dietary vitamin E (p=0.017) and the leptin/sOB-R ratio (p=0.046). Changes in vitamin A level were positively correlated with changes in dietary vitamin A (p=0.001) and RBP4 concentration (p=0.023). Associations between changes in RBP4 level with the changes in body mass index (BMI) (p=0.011) and total cholesterol concentration (p=0.023) but not with changes in vitamin A concentration were found in the obese after therapy. Conclusion: An increased risk of vitamin E deficiency may occur in children losing weight during lifestyle intervention. Changes in BMI value may influence changes in RBP4 concentrations and consequently the vitamin A status in obese children after therapy.

Associations between Maternal and Fetal Levels of Total Adiponectin, High Molecular Weight Adiponectin, Selected Somatomedins, and Birth Weight of Infants of Smoking and Non-Smoking Mothers.

The aim of the study was to determine the relationships between maternal smoking, total adiponectin, high molecular weight adiponectin (HMW adiponectin), selected somatomedins, and the birth weight of newborns. A total of 78 women with a healthy, singleton pregnancy, 41 active smokers and 37 non-smokers, and their offspring were studied. Total and HMW adiponectin, insulin-like growth factor I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) and 2 (IGFBP-2) were determined in maternal and cord blood by enzyme-link immunosorbent assay. Serum levels of total and HMW adiponectin were lower in smokers compared to the tobacco abstinent in both the mothers (p = 0.013; p = 0.006) and the infants (p = 0.001; p = 0.047). In smoking women and their children, serum concentrations of IGF-I were significantly lower (p = 0.014; p = 0.042), IGFBP-1 significantly higher (p = 0.009; p = 0.039), and IGFBP-2 did not differ from that observed in the non-smoking group. In multivariate analysis performed on the whole group of mothers, the highest impact of serum cotinine and IGFBP-2 levels were indicated for adiponectin and cotinine and the number of cigarettes/day for HMW adiponectin concentration. In correlation analysis estimated separately for smokers and non-smokers, neonatal birth weight was positively associated with total and HMW adiponectin concentrations in umbilical cord blood. Birth weight was also inversely associated with IGFBP-1 and positively correlated with IGF-I levels in maternal serum as well as in cord blood (r = -0.317, p = 0.005; r = -0.294, p = 0.004; r = 0.245, p = 0.031; r = 0.271, p = 0.009, respectively). The present study showed the levels of total and HMW adiponectin in umbilical cord blood may have a significant effect on fetal development. Both IGF-I and IGFBP-1 concentrations also play an essential role in fetal growth, which is an important predictor of birth weight. Cigarette smoking during pregnancy negatively affected adiponectin and the insulin growth factor profile in the serum of women and the cord blood and may be the reason for the lower birth weight of the smokers newborns compared with the nonsmokers offspring.

The Effect of the Ultra-Marathon Run at a Distance of 100 Kilometers on the Concentration of Selected Adipokines in Adult Men.

Pro-inflammatory adipokines have a multifunctional role in adipogenesis, angiogenesis, glucose homeostasis, and inflammation. The aim of the present study is to evaluate the effect of running a 100 km ultra-marathon on serum levels of two adipokines: resistin and chemerin. Fifteen male participants complete a medical questionnaire and their body composition is assessed. Serum resistin, chemerin, high sensitivity C-reactive protein (hs-CRP), glucose, and lactate levels are measured at baseline and post-race. During-race data on fluid and food consumption and energy expenditure are calculated. There is a higher (p < 0.001) post-race concentration of resistin and hs-CRP compared with resting values, with no change in chemerin levels. There is an inverse correlation of the change in resistin levels with post-run glucose values (r = 0.742, p < 0.001) and a positive correlation between changes in hs-CRP and energy expenditure (r = 0.782, p < 0.001). The present results show the impact of running an ultra-marathon on serum levels of pro-inflammatory markers released by adipose tissue. It is difficult to establish whether these results may be due to the stress of exercise, high energy expenditure or caloric deficit. However, we suggest that an addition of resistin to traditional pro-inflammatory markers (including CRP) may improve the assessment of inflammation in conditions of high-energy expenditure.

Active Tobacco Smoke Exposure in Utero and Concentrations of Hepcidin and Selected Iron Parameters in Newborns.

The aim of this study was to assess the influence of active tobacco smoke exposure in utero on the concentration of hepcidin and selected iron markers in umbilical cord blood and to evaluate the relationships between these parameters. Newborns of smoking mothers had significantly lower concentrations of serum hepcidin (p < 0.001), iron, and ferritin (p = 0.043; p = 0.042, respectively), but higher levels of erythropoietin (EPO, p < 0.001) and soluble transferrin receptor (sTfR, p = 0.011) compared with newborns of non-smoking women. Negative correlations between cotinine and the number of cigarettes smoked per day with hepcidin serum level (r = -0.33, p = 0.033, r = -0.32, p = 0.041, respectively) and EPO (r = 0.47, p = 0.002; r = 0.46, p = 0.003, respectively) were found. Univariate analysis defined for the whole group of children revealed significant associations between the concentration of hepcidin and other iron status parameters. In the models estimated separately for smokers and non-smokers, we found relations between the level of hepcidin and erythropoietin (B = -0.23, p = 0.004; B = -0.46, p = 0.01, respectively). In the multivariate regression model, a negative association between hepcidin and EPO concentrations in the whole group of newborns (ß = -0.53; p = 0.001) and in the group of smokers (ß = -0.57; p = 0.011) was confirmed. The present study shows significant relations between smoking during pregnancy and hepcidin levels in children born at term. Decreased cord serum concentrations of hepcidin associated with high erythropoietin levels suggest induced fetal erythropoiesis, probably due to the hypoxic effects imposed by maternal smoking.

Influence of Active Exposure to Tobacco Smoke on Nitric Oxide Status of Pregnant Women.

Smoking tobacco can impair proper vascular endothelial functioning. This is exhibited through reduced nitric oxide synthesis as well as activity due to accompanying oxidative stress. We examined the relationship between nitric oxide and markers of oxidative stress/antioxidant defense in serum of smoking and non-smoking pregnant women. Subjects included 99 healthy pregnant women, who were tested for nitric oxide (NO), endothelial (eNOS) and inducible (iNOS) nitric oxide synthase, total oxidant capacity (TOC), and total antioxidant capacity (TAC). NO, eNOS, and TAC serum concentrations were significantly lower (p < 0.005), but iNOS (p < 0.05) and TOC (p < 0.001) were higher in smokers than in non-smokers. Multivariate regression analysis showed associations between NO concentration and eNOS, TAC, and smoking status in the whole group of patients. In the model estimated separately for smokers, the highest impact of eNOS (ß = 0.375; p = 0.021) and cotinine (ß = -0.323; p = 0.037) was indicated for NO concentration. In the model of non-smokers, eNOS (ß = 0.291, p = 0.030) and TAC (ß = 0.350; p = 0.015) were important for NO level. Smoking during pregnancy could exacerbate oxidative stress, impair the action of nitric oxide synthases, and adversely affect the balance of oxygen and nitrogen metabolism. Relationships between NO concentrations and TAC in the studied women's blood can confirm the antioxidant nature of nitric oxide.

Ferroportin-Hepcidin Axis in Prepubertal Obese Children with Sufficient Daily Iron Intake.

Iron metabolism may be disrupted in obesity, therefore, the present study assessed the iron status, especially ferroportin and hepcidin concentrations, as well as associations between the ferroportin-hepcidin axis and other iron markers in prepubertal obese children. The following were determined: serum ferroportin, hepcidin, ferritin, soluble transferrin receptor (sTfR), iron concentrations and values of hematological parameters as well as the daily dietary intake in 40 obese and 40 normal-weight children. The ferroportin/hepcidin and ferritin/hepcidin ratios were almost two-fold lower in obese children (p = 0.001; p = 0.026, respectively). Similar iron concentrations (13.2 vs. 15.2 µmol/L, p = 0.324), the sTfR/ferritin index (0.033 vs. 0.041, p = 0.384) and values of hematological parameters were found in obese and control groups, respectively. Iron daily intake in the obese children examined was consistent with recommendations. In this group, the ferroportin/hepcidin ratio positively correlated with energy intake (p = 0.012), dietary iron (p = 0.003) and vitamin B12 (p = 0.024). In the multivariate regression model an association between the ferroportin/hepcidin ratio and the sTfR/ferritin index in obese children (ß = 0.399, p = 0.017) was found. These associations did not exist in the controls. The results obtained suggest that in obese children with sufficient iron intake, the altered ferroportin-hepcidin axis may occur without signs of iron deficiency or iron deficiency anemia. The role of other micronutrients, besides dietary iron, may also be considered in the iron status of these children.