Serum concentrations of sclerostin and bone turnover markers in children with cow's milk allergy.

THE AIM: of this study was to assess concentrations of sclerostin and biochemical markers of bone metabolism in children with cow's milk allergy. MATERIAL AND METHODS: The study included 45 children (age range 2-6 years) with diagnosed cow`s milk allergy, who were on a dairy-free diet and under systematic medical and dietary control at the Institute of Mother and Child in Warsaw. The control group consisted of 40 healthy children (2-6 years), who did not have any symptoms of cow`s milk allergy nor any diseases influencing bone metabolism. Their diets included milk and dairy products. Dietary intake of macro- and micronutrients was assessed based on 3-day records using the Dietetyk2® nutritional program. In the serum samples, we measured concentrations of calcium, phosphate and total alkaline phosphatase by standard methods, 25-hydroxyvitamin D3 by chemiluminescence method and bone metabolism markers by immunoenzymatic methods. The Statistica (version 10.0) computer software was used for statistical analysis. RESULTS: The nutritional status of studied children based on BMI value was normal. In all patients, the average daily value of dietary energy and percentage of energy from protein, fat and carbohydrates were consistent with the recommended values. The intake of calcium in the diets of all children was deficient, however, the intake of vitamin D was consistent with recommendations in the children with allergy, while in the healthy children it was below the recommended values. Mean serum concentrations of calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D3, osteocalcin and C-terminal telopeptide of type I collagen were similar in both studied groups. We observed significantly lower sclerostin levels in children with cow`s milk allergy (0.295±0.116 ng/ml) than in the healthy children (0.353±0.126 ng/ml) (p<0.05). The ratio of cytokines RANKL/OPG (receptor activator of nuclear factor κB ligand/osteoprotegerin) was significantly higher in children with allergy compared with their healthy counterparts (p<0.05). CONCLUSIONS: Basic laboratory parameters related to bone turnover in children with cow`s milk allergy, who were under medical and nutritional care, were normal. Reduced levels of sclerostin and increased ratio of cytokines RANKL/OPG may suggest disturbances in the balance between bone formation and bone resorption in these patients. Further research is needed on bone metabolism in children with food allergy, who due to the use an elimination diet may be at risk of developing abnormalities in the skeletal system.

Tobacco smoke exposure during pregnancy increases maternal blood lead levels affecting neonate birth weight.

To assess the effect of lead exposure from cigarette smoke on fetal growth, blood lead concentrations were measured using inductively coupled plasma mass spectrometry in 150 healthy pregnant women. Mean lead concentrations in plasma and whole blood were significantly higher in the smoking group compared with the nonsmoking group in each trimester of pregnancy (p < 0.001). Logistic regression analysis showed the highest impact of the number of cigarettes smoked per day for serum lead concentration (ß = 0.238; p < 0.05), while in whole blood, it was duration of smoking before conception (ß = 0.297; p < 0.001). Birth weight of the smoking mothers' infants was significantly lower (mean ± SEM, 3,192 ± 50.8 and 3,569 ± 49.6 g, respectively; p < 0.001) and negatively correlated with lead levels in plasma (r = -0.38; p < 0.001) and in whole blood (r = -0.27; p < 0.001). Therefore, it is suggested that smoking during pregnancy increases lead concentrations in maternal blood. Fetal exposure to low doses of lead in utero may be a serious risk factor causing lower birth weight.

[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.

[Assessment of selected bone metabolism marker concentrations in children with cystic fibrosis]. / Analiza stezen wybranych parametrów metabolizmu kostnego u dxieci chorych na mukowiscydoze.

AIM: The aim of this study was to assess bone formation and resorption processes and bone metabolism regulators, such as osteoprotegerin and fetuin-A in children with cystic fibrosis. MATERIAL AND METHODS: We examined 45 children with cystic fibrosis aged 5-13 years treated at the Institute of Mother and Child in Warsaw. The control group consisted of 35 healthy children in the same synage range without any diseases which may influence bone metabolism. We determined serum calcium and phosphate levels by colorimetric methods, vitamin D3 by the chemiluminiscence method and bone metabolism markers (osteocalcin, 5b isoenzyme of tartrate-resistant acid phosphatase, osteoprotegerin, fetuin-A) by immunoenzymatic methods. RESULTS: Mean serum concentrations of calcium and phosphate in the studied children were within the reference ranges. However, the level of 25-hydroxyvitamin D3 was significantly lower in patients with cystic fibrosis compared to the controls (19.3±7.6 vs 25.2±8.9 ng/ml, p<0.01). In cystic fibrosis children we observed a statistically significant lower concentration of osteocalcin (81.9±28.9 vs 97.9±28.6 ng/ ml, p<0.01) and similar activity of 5b isoenzyme of tartrate-resistant acid phosphatase (12.5±2.9 vs 13.4±3.5 U/L) as compared to healthy peers. Mean serum concentration of osteoprotegerin in patients with CF was significantly lower than in the control children (4.1±0.98 vs 4.59±0.86 pmol/l, p<0.05). Serum concentration of fetuin-A was comparable in both groups of children. CONCLUSIONS: In children with cystic fibrosis changes in the profile of bone metabolism markers were observed. Even patients with CF who are clinically stable and supplemented with vitamins are at risk of osteopenia and osteoporosis in their later life. Therefore, they should be under a comprehensive medical and nutritional care in order to achieve their optimal peak bone mass.

The pregnancy-associated plasma protein A and insulin-like growth factor system in response to cigarette smoking.

OBJECTIVE: Maternal smoking during pregnancy is associated with a reduction in birth size but the mechanism by which this occurs still remains unclear. The purpose of this study was to evaluate the effect of tobacco smoking on concentrations of pregnancy-associated plasma protein A (PAPP-A), insulin-like growth factor I (IGF-I), II (IGF-II) and binding proteins BP-3 and BP-4 in pregnant women and correlations between these parameters. METHODS: Sixty healthy pregnant women were divided into smoking and tobacco-abstinent group according to results of serum cotinine concentration. The current smokers were defined as those who had smoked five or more cigarettes per day during pregnancy. RESULTS: The mean serum concentrations of PAPP-A, IGF-I and IGF-II were significantly lower in smoking than in non-smoking pregnant women (p < 0.01). The level of PAPP-A correlated positively with the IGF-II concentration in both studied group (non-smoking: r = 0.54; p < 0.001; smoking: r = 0.40; p < 0.05). In tobacco-abstinent group negative correlation between IGF-II and IGFBP-4 concentrations was found (r = -0.35; p < 0.05). CONCLUSION: Tobacco smoking during pregnancy decreases the pregnancy-associated plasma protein A and insulin growth factors I and II levels. The correlation between PAPP-A and IGF-II may suggest function of this protein as a protease and regulator in the IGF system.

[Effect of cigarette smoking on blood lead levels in pregnant women]. / Wplyw palenia tytoniu na poziom olowiu we KRWI kobiet ciezarnych.

UNLABELLED: Tobacco smoking creates health problems which apply not only to individuals and the family but also to different ages and social groups, as well as the national economy. Epidemiologic studies conducted at the Institute of Mother and Child indicated that in Poland 25-30% women smoke during pregnancy. Lead exposure from cigarette smoke may have a negative effect on the transplacental flow of micronutrients and have an adverse influence on the growth and development of the fetus, and then on children. The aim of this study was to estimate the effect of smoking cigarettes on plasma and whole blood lead levels in pregnant women. MATERIAL AND METHODS: Eighty healthy pregnant women, patients of the Clinical Department of the Obstetrics and Gynecology Institute of Mother and Child and Warsaw Medical University, were divided into two groups: group I - tobacco smokers and group II- tobacco abstainers according to questionnaire declaration and serum cotinine concentration. Current smokers were defined as those who had smoked 5 cigarettes per day for 2 years before conception and continued smoking during pregnancy. The women exposed to environmental tobacco smoke (smoking spouse or other family members, co-workers) were excluded from the non-smoking group. All pregnant volunteers signed a written, informed consent form, approved by the Institute's Ethical Committee. The concentrations of lead in plasma and whole blood were analyzed using inductively coupled plasma mass spectrometry on spectrometer analyzer ICP MS Elan 6100 (Perking Elmer, Germany). Levels of cotinine in serum were determined by Cotinine Direct ELISA test (Calbiotech Inc. Canada). RESULTS: In the group of smoking mothers the mean serum cotinine concentration was 69.1 µg/L, whereas in the group of tobacco abstainers it was present only in trace amount. In group I we observed a significant positive correlation between serum cotinine and the number of cigarettes smoked daily (r=0.74; p<0.001), as well as the period of smoking before conception (r=0.60; p<0.001). The concentrations of lead in the plasma of smoking women were significantly higher than in the group of tobacco abstainers in each trimester of pregnancy (I trimester: 0.22 µg/dL vs 0.12 µg/dL p<0.01; II trimester: 0.19 µg/L vs 0.10 µg/L p<0.001; III trimester 0.28 µg/ dL vs 0.13 µg/dL p<0.0001). Tobacco smoking mothers also had a higher concentration of lead in whole blood as compared to pregnant non-smoking women. These differences were statistically significant and amounted to 2.15 µg/dL vs 1.28 µg/L in the first, 1.99 µg/dL vs 1.19 µg/dL in the second and 2.11 µg/dL vs 1.58 µg/dL in the third trimester of pregnancy. We observed that the level of lead was correlated with cotinine in blood, as well as with the number of cigarettes and the length of time women smoked before conception. Such an effect was observed in every trimester of gestation. A strong correlation between the number of cigarettes/day and lead concentration in plasma (r=0.57; p<0.001) and whole blood (r=0.54; p<0.001) was found in the third trimester of pregnancy. CONCLUSIONS: Tobacco smoking during pregnancy increased the concentrations in maternal blood lead. The level of lead in plasma and whole blood correlated with the degree of intensity of cigarette smoking in the pregnant women studied. It may be a result of influencing the mobilization of calcium from the bone with simultaneous release of lead deposited in the bone. Further studies are required to characterize the effect of higher lead level in the blood of mothers on the risk of premature labor, low birth weight of newborns and their inferior development.

The effect of tobacco smoking during pregnancy on plasma oxidant and antioxidant status in mother and newborn.

OBJECTIVE: The aim of the study was to estimate the effect of tobacco smoking during pregnancy on oxidative damage and antioxidant defence in matched samples of maternal blood and cord blood. STUDY DESIGN: Healthy, pregnant women (n=140) were divided into non-smoking and smoking groups according to the concentration of cotinine in serum and urine. Oxidative damage was measured through levels of malondialdehyde (MDA) and plasma antioxidant status was evaluated by measuring concentrations of total radical trapping parameters (TRAP) and selected antioxidants (ß-carotene, vitamin A, vitamin E, uric acid). Statistical analysis was done using the SAS System for Windows (SAS Institute, Cary, NC). RESULTS: In the course of pregnancy the concentration of MDA increased, but to higher values in smoking women than in non-smoking ones. It was accompanied by significantly lower TRAP in the smoking group than in the controls (p<0.05). Plasma concentration of uric acid (p<0.05) and antioxidant vitamins E (p<0.01), A and ß-carotene (p<0.0001) were all reduced in smokers as compared with non-smoking pregnant women especially in the third trimester. Concentration of MDA in plasma of cord blood of newborns of smoking mothers was significantly higher (p<0.01) but the antioxidant defence was lower (p<0.0001) than in non-smoking ones. It was particularly pronounced for ß-carotene (32%; p<0.0001) and vitamin A (28%; p<0.001). A significant negative correlation was found between MDA and TRAP levels of maternal plasma (non-smoking and smoking: r=-0.50, p<0.0001) and cord plasma (non-smoking: r=-0.54, p=0.0057; smoking: r=-0.71, p=0.0004) in all the study subjects. Total antioxidant status positively correlated with concentrations of uric acid and vitamin E in non-smoking and smoking mothers as well as their newborns. CONCLUSION: Tobacco smoke enhances lipid peroxidation and depletes antioxidant potential in the plasma of pregnant women and umbilical cord blood. Therefore smoking during pregnancy may stimulate free radical damage in the mother and the growing fetus.

[Influence of vegetarian diet on serum values of homocysteine and total antioxidant status in children]. / Wplyw stosowania diety wegetarianskiej na stezenie homocysteiny oraz calkowita aktywnosc przeciwutleniajaca w surowicy u dzieci.

UNLABELLED: The vegetarian diet may play a preventive role in the development of chronic diseases such as coronary heart and cardiovascular disease. However increase of homocysteine (Hcy) concentration in peoples avoiding animal products may contribute to an increased atherosclerotic risk in these subjects. Recent evidence has suggested that role of hyperhomocysteinemia in atherogenesis is associated with process of autooxidation, which can promote the production of hydroxyl radicals, resulting in oxidative modification of low density lipoprotein and endothelium injury. The oxidant-antioxidant imbalance depends not only on the amount of enhanced free oxygen species but also insufficiency of antioxidant defence system. Total antioxidant status (TAS) expresses capacity for scavenging of free radicals minimizes oxidative damage. The aim of this study was to asses concentrations of homocysteine and total antioxidant status in serum of children on vegetarian and omnivorous diet. We also studied levels of vitamin A (retinol) and vitamin E (alpha-tocopherol) particular components of TAS. MATERIAL AND METHODS: The study included 35 children, aged 5-16 who had been referred to Institute of Mother and Child for dietary consultation. From those, 17 were lacto-ovo-vegetarians and 18 omnivores. Dietary constituents were analyzed using the nutritional programme Dietetyk2 and completed with supplementation data. Concentration of homocysteine was estimated in serum with fluorescence polarization immunoassay and TAS by colorimetric method. Levels of vitamin A and E were determined using high-pressure liquid chromatography (HPLC). RESULTS: The mean concentration of homocysteine was similar in both studied groups (vegetarians: 6.13 +/- 1.01 micromol/l vs. omnivores: 5.45 +/- 0.98 micromol/l). In vegetarian children serum level of TAS was significantly lower (1.21 +/- 0.06 mmol/I) as compared to those in non-vegetarian ones (1.30 +/- 0.05 mmol/l, p < 0.0001), but remained within the physiological range (1.16-1.40 mmol/l). The mean concentrations of vitamins A and E in serum of vegetarians were lower than observed in omnivores group, but only in case of alpha-tocopherol the difference was statistically significant (vegetarians: 15.58 +/- 4.12 vs. omnivores: 18.41 +/- 3.10; p < 0.05). CONCLUSION: In studied group of children on lacto-ovo-vegetarian diet, serum concentrations of homocysteine are normal and daily food intake of antioxidants and their level in blood are sufficient for preserving adequate total antioxidant status.

[A comparison of serum concentrations of biochemical bone turnover markers in patients with osteosarcoma with good and poor prognosis]. / Analiza stezenia biochemicznych markerów obrotu kostnego u chorych na miesaka kosciopochodnego z korzystnym i niekorzystnym rokowaniem.

UNLABELLED: Osteosarcoma is a primary malignant bone tumor, whose peak incidence occurs in the second decade of life during the adolescent growth spurt. Complex oncological treatment consisted of chemotherapy combined with surgery which substantially increased the cure rate of patients with osteosarcoma, but it is very important to identify patients with poor prognosis and to treat them with more aggressive therapy. THE AIM OF THIS STUDY: To assess serum biochemical bone turnover markers as prognostic indicators in patients with osteosarcoma. MATERIAL AND METHODS: We studied 55 patients from age 5 to 20 years with diagnosed osteosarcoma treated at the Institute of Mother and Child in Warsaw. The studied group was divided into 2 subgroups consisted of 27 patients with favorable (disease remission) and 28 patients with unfavorable (disease progression) prognosis. Venous blood was collected from patients in the morning hours at time of diagnosis, during anticancer treatment and after completion of treatment. Serum osteocalcin (OC), bone alkaline phosphatase (BALP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were analyzed by immunoenzymatic methods. RESULTS: At time of diagnosis, in patients with unfavorable prognosis concentration of bone formation markers were higher (OC by 30% and BALP by 60%) than in those with good prognosis, however, CTX level was similar in both groups of patients. During chemotherapy in patients with poor prognosis we observed higher levels of bone turnover markers in comparison to subjects with favorable prognosis. After the completion of therapy, in patients with progression median values of bone formation markers were over twofold and bone resorption marker about 50% higher as compared to patients with remission of disease. These differences were statistically significant at p < 0.05 for OC, p < 0.001 for BALP and p < 0.01 for CTX. CONCLUSIONS: Our results suggest that bone turnover markers, especially bone alkaline phosphatise may be useful in the monitoring and in the assessment of the efficacy of therapy in children with osteosarcoma. Higher rates of bone formation and resorption during treatment and after its completion are associated with unfavorable prognosis and may indicate progression of disease.

[Evaluation of iron balance in healthy pregnant women and their newborns]. / Badanie gospodarki zelazem u kobiet w przebiegu ciazy niepowiklanej oraz we krwi pepowinowej ich dzieci.

AIM OF THE STUDY: The aim of this study was to evaluate the iron status markers in normal healthy pregnancy as well as the influence of maternal diet on iron concentration in their newborns. MATERIAL AND METHODS: A longitudinal prospective study was conducted in a sample of 69 healthy non-smoking pregnant women under prenatal care of The Institute of Mother and Child. Blood samples were collected in the first, second and third trimesters and from the umbilical vein. Concentrations of ferritin and transferrin were assessed using turbidimetric technique, the concentration of iron--with ferrozine colorimetric method. Pentra 120 analyzer was used to define hematological parameters. Maternal diet was assessed by means of a weekly questionnaire, processed with computer software Dietetyk 2. RESULTS: Hematological parameters in the analyzed blood were normal. The average hematocrit values in the first trimester of pregnancy was 36.7%, in the second--34.92%, in the third--35.95%. The concentration of hemoglobin was 27.82 g/dl, 28.55 g/dl, 27.27 g/dl in the respective trimesters of pregnancy. In the umbilical blood it was 25.84 g/dl (5.2% less than in the maternal blood). The number of erythrocytes was the highest in the first (4.16 mln/mm3), and the lowest in the second trimester (3.92 mln/mm3). The average concentration of iron was the highest in the first trimester--99.61 microg/dl. In the second and third trimester it decreased by 25% and 2% respectively. The concentration was 76.34% higher in the umbilical blood than in maternal blood at the time of labor. The concentration of ferritin in the first trimester was 43.96 microg/l, in the second and the third trimester it was lower by 46% and 29% respectively. It was 126.4 microg/l in the umbilical blood (fourfold higher than in maternal blood). The concentration of transferrin was 321.01 mg/dl in the first trimester and it increased in consecutive trimesters by 36.14% and 5.12%; it was 219.92 mg/dl in the umbilical blood--48% of the concentration of transferrin in the maternal blood at the time of labor. The analysis of an average daily food ration revealed that the supply of iron was 80% of the recommended dose in the first half and only 41% of the recommended dose in the second half of the pregnancy. Fat consumption was 99% and 95% of the recommended dose, respectively. There was a 30%-decrease in the protein and carbohydrates consumption in comparison with the recommended dose in the second half of the pregnancy. CONCLUSIONS: In spite of normal hematological parameters, we observed insufficient supply of iron in the diet of pregnant women, which was demonstrated by a decreased level of ferritin. It should be reason enough to issue dietary recommendations and guidelines for pregnant women in each stage of pregnancy.