Relationship between Iron-Related Parameters and Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis in Obese Children

Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. 43 children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by the World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children, whose BMI percentile values were between 99 and 95, comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analyses, including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %) and ferritin, were performed. sTWEAK levels were determined by enzyme-linked immunosorbent assay. study data were evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91 ± 34 mcrg/dl and 75 ± 31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs. 299 mcrg/dl, 37.2 ± 19.1% vs. 26.7 ± 14.6%, and 41 ± 25 ng/ml vs 44 ± 26 ng/ml. In N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p > 0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p < 0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is an inducer of apoptosis. OB children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of OB children.

Measurements of MRI R2* Relaxation Rate in Liver and Muscle: Animal Model

This study was aimed to measure effective transverse relaxation rates (R2*) in the liver and muscle of normal New Zealand White (NZW) rabbits. R2* relaxation rate has been widely used in various hepatic diseases for iron overload by quantifying iron contents in liver. R2* relaxation rate is defined as the reciprocal of T2* relaxation time and mainly depends on the constituents of tissue. Different tissues would have different R2* relaxation rates. The signal intensity decay in Magnetic resonance imaging (MRI) may be characterized by R2* relaxation rates. In this study, a 1.5T GE Signa HDxt whole body MR scanner equipped with an 8-channel high resolution knee coil was used to observe R2* values in NZW rabbit’s liver and muscle. Eight healthy NZW rabbits weighted 2 ~ 2.5 kg were recruited. After anesthesia using Zoletil 50 and Rompun 2% mixture, the abdomen of rabbit was landmarked at the center of knee coil to perform 3-plane localizer scan using fast spoiled gradient echo (FSPGR) pulse sequence. Afterwards, multi-planar fast gradient echo (MFGR) scans were performed with 8 various echo times (TEs) to acquire images for R2* measurements. Regions of interest (ROIs) at liver and muscle were measured using Advantage workstation. Finally, the R2* was obtained by a linear regression of ln(sı) on TE. The results showed that the longer the echo time, the smaller the signal intensity. The R2* values of liver and muscle were 44.8 ± 10.9 s-1 and 37.4 ± 9.5 s-1, respectively. It implies that the iron concentration of liver is higher than that of muscle. In conclusion, the more the iron contents in tissue, the higher the R2*. The correlations between R2* and iron content in NZW rabbits might be valuable for further exploration.

Status of Thyroid Function and Iron Overload in Adolescents and Young Adults with Beta- Thalassemia Major Treated with Deferoxamine in Jordan

Thyroid dysfunction is one of the most frequently reported complications of chronic blood transfusion therapy in patients with beta-thalassemia major (BTM). However, the occurrence of thyroid dysfunction and its possible association with iron overload in BTM patients is still under debate. Therefore, this study aimed to investigate the status of thyroid functions and iron overload in adolescent and young adult patients with BTM in Jordan population. Thirty six BTM patients aged 12-28 years and matched controls were included in this study. All patients have been receiving frequent blood transfusion to maintain pretransfusion hemoglobin concentration above 10 g dl-1 and deferoxamine at a dose of 45 mg kg-1 day-1 (8 h, 5-7 days/week) by subcutaneous infusion. Blood samples were drawn from patients and controls. The status of thyroid functions and iron overload was evaluated by measurements of serum free thyroxine (FT4), triiodothyronine (FT3), thyrotropin (TSH) and serum ferritin level. A number of some hematological and biochemical parameters were also measured. It was found that hematocrit, serum ferritin, hemoglobin, FT3 and zinc, copper mean values were significantly higher in the patients than in the controls (P< 0.05). On other hand, leukocyte, FT4 and TSH mean values were similar to that of the controls. In addition, our data also indicated that all of the above examined parameters were not significantly affected by the patient-s age and gender. Deferoxamine approach for removing excess iron from our BTM patient did not normalize the values of serum ferritin, copper and zinc, suggesting poor compliance with deferoxamine chelation therapy. Thus, we recommend the use of a combination of deferoxamine and deferiprone to reduce the risk of excess of iron in our patients. Furthermore, thyroid dysfunction appears to be a rare complication, because our patients showed normal mean levels for serum TSH and FT4. However, high mean levels of serum ferritin, zinc, copper might be seen as potential risk factors for initiation and development of thyroid dysfunctions and other diseases. Therefore, further studies must be carried out at yearly intervals with large sample number, to detect subclinical thyroid dysfunction cases.