[Show abstract][Hide abstract] ABSTRACT: Childhood obesity and the Metabolic Syndrome (MetS) are associated with an increased risk for early onset endothelial dysfunction and atherosclerosis. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in atherosclerosis by stimulating angiogenesis and atherogenic migration of monocytes/macrophages into the arterial wall. The aim of this study was to investigate differences in circulating PlGF concentrations between children with obesity/metabolic syndrome and non-obese children. We have previously shown increased high-sensitivity troponin (hs-TnT) concentrations in children with MetS from the same cohort.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Childhood obesity is associated with an increased risk for atherosclerosis mediated by the pathogenetic mechanisms that lead to the development of the Metabolic Syndrome (MetS). High-Sensitivity Troponin T (hs-TnT) is a specific marker of ischemic myocardial damage, whereas a minimal elevation of this biomarker has been found in adults with a high-risk for cardiovascular disease. We hypothesized that hs-TnT might be altered in obese children with and/or without the Mets. MATERIALS AND METHODS: Fifty-seven (34 males) obese and 25 non-obese (6 males) children were assessed at the Childhood Obesity Clinic of our department. Obesity was defined using the IOTF criteria. Metabolic syndrome was defined with the IDF criteria. Hs-TnT was measured using an electrochemiluminescence-based assay. RESULTS: The entire group of obese children had significantly higher hs-TnT concentrations [4.1 ± 3.4 ng/L] (p=0.029) than the non-obese ones [3.0 ± 0.2 ng/L), however, in both groups the levels of the cardiac biomarker were within the normal range. Comparison of the obese children with or without the MetS and the non-obese, revealed that those with the MetS had significantly higher hs-TnT (6.7±7.1 ng/L) than the obese without MetS (3.7 ± 2.1 ng/L) [p=0.044], and the non-obese [p=0.014]. Hs-TnT did not differ between the obese without MetS and the non-obese. CONCLUSIONS: Circulating concentrations of hs-TnT in obese children with the MetS are higher than those of the obese without the MetS and the non-obese, suggesting that it is obesity-related metabolic changes rather than obesity per se linked to increased hs-TnT in children.
Metabolism: clinical and experimental 10/2012; · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Iron-induced cardiotoxicity remains the leading cause of morbidity and mortality in patients with transfusion-dependent β-thalassemia major. Heart failure in these patients, which may be reversible but has a poor prognosis, is characterized by myocardial iron deposition-related early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic left ventricular dysfunction. In this study, we prospectively evaluated plasma NT-proBNP levels in 187 adult patients aged 19-54years with β-TM. Possible correlations with the proposed recently cardiac iron concentration based on an equation derived from heart T2* assessment by MRI: [Fe]=45.0×[T2*](-1.22) with [Fe] in milligrams per gram dry weight and T2* in milliseconds were explored. We found that: 143 patients had no cardiac hemosiderosis, defined as [Fe]<1.1mg/g dry weight, corresponding to T2*>20ms and 44 patients had cardiac hemosiderosis, defined as [Fe] >1.2mg/g dry weight. The main results of the study showed that: a) NT-proBNP levels were markedly increased in thalassemic patients (152.2±190.1pg/mL, ranged from 6.0 to 1336.0pg/mL compared to normal control levels 40.1±19.7pg/mL, p<0.001, b) NT-proBNP levels were significantly higher in patients with cardiac hemosiderosis compared to patients without cardiac hemosiderosis (185.1±78.0 vs 128.9±20.2pg/mL, p<0.05), c) NT-proBNP levels correlated with [Fe] values (r=0.387, p<0.001). This correlation was significant in patients with cardiac hemosiderosis (r=0.520, p<0.001), but not in patients without cardiac hemosiderosis (p>0.1), and d) no significant correlation was found between NT-proBNP levels and left ventricular ejection fraction values, (p>0.3). Our study demonstrated for first time the significant association of NT-proBNP levels and cardiac iron concentration in patients with β-thalassemia major linking blood chemistry and imaging techniques. Multicenter studies of these parameters during iron chelation therapies are needed to validate their association and further exploit its clinical use.
Blood Cells Molecules and Diseases 09/2012; · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disturbances of oxidative stress and antioxidant status have been reported in patients with Β-ThM and in a limited number of patients with ThI.
To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype.
Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused.
Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly significant positive correlation with age (p〈0.001) and sTfR. Biomarkers with oxidant activity were also significantly increased in ThI patients compared to controls; significantly higher levels for MDA, NTBI, and GSSG/GSHT were found in severe ThI. The activity of antioxidant enzymes GR, GP and SOD, was significantly significantly reduced in patients, especially in the severe type. Vitamin C was mildly reduced in both types of ThI.
Activity of relevant biomarkers of iron and oxidant-antioxidant homeostasis was significantly increased in untransfused patients with ThI. These changes coincide with the severity of clinical phenotype, genotype and bone marrow erythroid activity evaluated by sTfR levels.
Pediatric endocrinology reviews: PER 03/2011; 8 Suppl 2:256-62.
[Show abstract][Hide abstract] ABSTRACT: Continuous reactive oxygen species (ROS) production in individuals with sickle cell disease (SCD) may alter their overall redox status and cause tissue damage. The aim of this study was to evaluate oxidative stress in patients with SCD using two new assays, FORT (free oxygen radical test) and FORD (free oxygen radical defense) along with assessment of glutathione system including superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities, vitamins A, C and E, malondialdehyde (MDA), non-transferrin bound iron (NTBI) and nitric oxide (NO) concentrations. A total of 40 patients with SCD and 25 apparently healthy volunteers (control group) were enrolled in the study. Components of glutathione system, vitamins A, C, and E, and malondialdehyde were determined with reverse-phase HPLC, non-transferrin bound iron (NTBI) was assessed with atomic absorption spectroscopy using graphite furnace, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities were determined spectrophotometrically in red cell lysates, nitric oxide (NO) was detected colorimetrically, while FORT and FORD using colorimetric assays, as two point-of-care tests. The findings revealed significant impairment of the glutathione system indicated by reduced GSH(total) (p<0.00001), GSH(reduced) (p<0.00001) and GSSG (p>0.056) values of SCD patients compared to the control group. ROS expressed as FORT were significantly increased (p<0.00001), while antioxidant defense expressed as FORD was significantly reduced (p<0.02) in SCD group compared to the control group. Age and genotype of the patients as well as therapy of their disease appeared to play no role in their oxidative status.
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Serum placental growth factor (PlGF) concentrations have been reported to be elevated in patients with sickle cell disease (SCD). sFlt-1 binds to and sequesters circulating free VEGF and free PlGF, thereby neutralizing their pro-angiogenic effects. Perturbations of the proangio-and anti-angiogenic balance lead to endothelial dysfunction, common in patients with hemoglobinopathies. We assessed the PlGF and sFlt-1 levels in patients with hemoglobinopathies at steady state.
The findings indicate that patients with thalassemia syndromes and SCD appear to have an increased degree of angiogenesis. The decreased sFLT-1/PlGF ratio suggests that the proangio-and anti-angiogenic balance is shifted towards the former, providing evidence that patients with hemoglobinopathies even in the steady phase have altered angiogenic state and low-grade inflammation.
51st American Society of Hematology Annual Meeting 2009; 03/2010
[Show abstract][Hide abstract] ABSTRACT: Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome.
To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain.
Prospective cohort study.
55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group).
Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life.
Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (beta=0.33; p=0.01 and beta=0.33; p=0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (beta=0.36, p=0.01).
An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.
Early human development 03/2010; 86(4):197-201. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study circulating levels and distribution of adiponectin multimers [low molecular weight (LMW)-, medium molecular weight (MMW)- and high molecular weight (HMW)-adiponectin] in preterm and full-term infants.
Total serum adiponectin and its multimers were measured in 40 healthy infants at the age of one month and associations with anthropometric parameters [body weight and length, body mass index (BMI)], weight gain and metabolic indices (glucose, insulin) were examined. Twenty of the infants were born preterm (gestational age 33.2+/-1.6 weeks).
LMW-adiponectin level and its fractional ratio to total adiponectin were significantly higher in full-term than in preterm infants (P<0.001 and P<0.01, respectively), whereas, MMW-adiponectin level and its ratio were significantly lower (P=0.03 and P=0.01, respectively). HMW-adiponectin did not differ significantly between full-term and preterm infants and accounted for almost 60% of total adiponectin levels in both groups. HMW-adiponectin, but not MMW adiponectin or LMW adiponectin, correlated significantly with anthropometric measurements, similarly to total adiponectin; in addition, HMW adiponectin correlated significantly with weight gain.
HMW adiponectin is the most prevalent form in infants. Circulating levels and distribution of MMW- and LMW-adiponectin differ between full-term and preterm infants, but the role of these adiponectin multimers needs to be studied further.
Journal of Perinatal Medicine 07/2009; 37(6):683-8. · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the levels of free oxygen radicals and free oxygen radicals defense in patients with newly diagnosed type 2 diabetes mellitus (T2DM). The disease seems to be involved strongly in the production of reactive oxygen species. Forty-five patients with newly diagnosed T2DM and 20 apparently healthy individuals (control group) were included in the study. Reactive oxygen species were determined using the free oxygen radicals (FORT) test, which is based on the Fenton reaction. In this method, the hydroperoxides reacted with the transition metal ions liberated from the proteins and were converted to alkoxy and peroxy radicals. The radical species produced by the reaction, which are directly proportional to the quantity of lipid peroxides, interact with an additive that forms a radical molecule. Similarly, the free oxygen radicals defense (FORD) test uses preformed stable and colored radicals and determines the decrease in absorbance that is proportional to the blood antioxidant concentration. We found that (a) FORT levels were increased in diabetic patients (2.86 +/- 0.56 mmol/L H(2)O(2)) compared with controls (1.87 +/- 0.26 mmol/L H(2)O(2)) (P < .0001) and (b) FORD levels were lower in diabetic patients (1.23 +/- 0.18 mmol/L Trolox) compared with controls (1.34 +/- 0.14 mmol/L Trolox) (P < .01). The intraassay and interassay coefficients of variation were 3.7% and 6.2%, respectively, for FORT and 4.2% and 6.6%, respectively, for FORD. Determination of free oxygen radicals and free oxygen radicals defense seems to play an important role in the generation and evaluation of oxidative stress, an imbalance between oxidants and antioxidants that can lead to oxidative damage and is involved in the pathogenesis of several diseases, such as T2DM.
Metabolism: clinical and experimental 07/2009; 58(11):1657-62. · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess and compare the individual effect of different chelation agents on urinary iron excretion (UIE), we asked every patient, receiving combined chelation treatment with deferiprone (DFP) and deferoxamine (DFO), to provide four 24-hours urine samples; 2 samples were collected during days when patient was receiving only DFP, whereas the other 2 were collected when both chelation agents were administrated. Thirty young patients (15 males and 15 females) with beta-thalassemia major and a mean age of 18.54+/-4.62 years participated in the study. Mean serum ferritin concentrations were calculated 1 year prior and 1 year after the urine collection. A significant reduction in ferritin (P=0.001) was shown in the whole patients' series. Combined administration of DFO and DFP resulted in a statistically significant higher UIE than DFP alone (P=0.0007). On an individual basis, DFO and DFP resulted in a median 2.3-fold increase in UIE compared to monotherapy with DFP, ranging from 0.28 to 7.34-fold. Despite this wide variability, combined chelation treatment with DFO and DFP seems to act additively in the majority of the patients, whereas in some patients the huge increase in UIE with DFO and DFP can only be attributed to a synergistic effect.
Journal of Pediatric Hematology/Oncology 10/2007; 29(9):598-601. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic studies have indicated a relationship between serum lipids and cancer, and it is possible that lipid abnormalities are involved in the mechanism of oncogenesis. This study was performed to investigate serum lipid alterations in patients with acute lymphoblastic leukemia (ALL) at diagnosis and during remission of the disease. Plasma lipids and lipoproteins were measured at diagnosis, prior to the administration of induction treatment, and every 2 months for the first 12 months of the maintenance phase of chemotherapy in 64 patients with ALL. Nearly all patients demonstrated a predictable pattern of serum lipid alterations that consisted of extremely low levels of high-density lipoprotein cholesterol, elevated triglycerides, and elevated low-density lipoprotein cholesterol. Patients studied again during remission demonstrated a return to normal values, and the difference was statistically significant. The results suggest that at diagnosis of ALL an abnormality in lipid metabolism is present, which is reversed during remission.
Journal of Pediatric Hematology/Oncology 06/2004; 26(5):289-93. · 0.97 Impact Factor