Oxidative stress and hepcidin expression in pediatric sickle cell anemia with iron overload.

BACKGROUND: Blood transfusion (BT) is essential in treating sickle cell disease (SCD); however, it leads to iron overload (IO) and oxidative stress. We studied the relationship between oxidative stress, iron status parameters, hepcidin mRNA gene expression, and IO in SCD patients. METHODS: We classified all SCD patients (n = 90) into two groups: Group I, 45 children (s.ferritin ≥ 938 ng/mL) and Group II, 45 children (s.ferritin < 938 ng/mL). A total of 55 children, age and sex matched, participated as a control group. Malondialdehyde (MDA), nitrite, s.iron, s.total iron-binding capacity (sTIBC), transferrin saturation %, s.ferritin, s.hepcidin, and hepcidin mRNA gene expression were assessed. RESULTS: Among SCD BT-dependent patients (>3 times/year), 63% were from Group I and 37% from Group II, p < .01. The two patient groups had significantly lower s.hepcidin and hepcidin gene expression than controls ( p < .001). TIBC, s.iron, s.ferritin, transferrin saturation %, ferritin/hepcidin ratio, and MDA levels were higher among SCD patients than controls ( p < .001). Group I had higher mean level of ferritin/hepcidin ratio and MDA than Group II ( p < .01). The higher level of MDA and increased frequency of BT were the significant predicting risk factors for IO ( p < .05). A receiver-operating characteristic curve indicates that MDA is the outstanding significant biomarker for high level of s.ferritin with subsequent IO progression. CONCLUSION: MDA may serve as a biomarker of oxidative stress and IO in SCD patients. This result paid attention for urgent initiation of antioxidant and chelation therapy on detecting increased MDA level.

Association of some dietary ingredients, vitamin D, estrogen, and obesity polymorphic receptor genes with bone mineral density in a sample of obese Egyptian women.

BACKGROUND: Although many environmental factors play an important role in bone mass density (BMD) variation, genetic influences account for 60-85% of individual variance. The aim of this study was to find the interaction between some dietary ingredients, vitamin D, estrogen, and obesity polymorphic receptor genes, among a sample of obese Egyptian women. This was a cross sectional study included 97 women (aged 25-60 years). Data on anthropometry, dietary intake, BMD, biochemical, and genetic analyses were collected. RESULTS: Osteoporosis was high among women had dominant Taq1 vitamin D receptor gene while osteoporosis was less common among the homozygous Apa1 receptor gene women. Both genes in their two forms did not show any effect on serum vitamin D. Heterozygous types of osteoporotic women carried both genes revealed a slight but significant decrease in level of serum calcium. Xba1 estrogen receptor gene was identified only in a homozygous type while the heterozygous Pvu11 estrogen receptors gene has been identified among both osteoporotic and non-osteoporotic women, this gene was associated with higher BMI in both groups compared to the homozygous receptor gene. Mutant types of genotype FTOrs99 and FTOrs80 obesity receptors genes were less common (4.44%, 11%) among participants. Both of these genes were associated with the highest value of BMI and caloric daily intake, fat, and saturated fatty acid that were more prominent among osteoporotic women. CONCLUSION: There is significant association between vitamin D, estrogen, obesity receptors genes, special nutrients, and osteoporosis. Increased BMI, calories, and fat intake lead to rise of genetic predisposition and susceptibility to osteoporosis.

Dietary Pattern and Bone Health in Pre and Post-menopausal Obese Women.

BACKGROUND AND OBJECTIVE: Obesity and osteoporosis are worldwide health problems that interact with each other. There are also affected by the menopause and dietary pattern. So, this study aimed to find the relation between osteoporosis, body weight and intake of protein, calcium and vitamin D in obese pre and post-menopausal women. MATERIALS AND METHODS: One hundred and sixteen shared as volunteers in a cross-section study lasted for 2 years. They were divided into 2 groups, pre and post-menopausal women. All women were subjected to, clinical examination, anthropometric measurements and 24 dietary recalls. They were evaluated for bone mass density, biochemical analysis for serum lipids, calcium and vitamin D. RESULTS: Osteopenia and osteoporosis were higher among normal-weight and overweight (non-obese) women compared to obese as well weakly associated with their serum lipids. The mean daily protein consumption was high as compared to recommended daily allowances (RDAs), especially among osteoporotic women. The mean daily intake of vitamin D and calcium was low as the lower level was noticed among the osteoporotic premenopausal patients. The means serum concentration of calcium and vitamin D were adequate. CONCLUSION: Data revealed that the prevalence of osteoporosis was lower among obese patients compared to non-obese women. Inadequate daily dietary intake of calcium and vitamin D was reported, however, physiological compensation maintained their optimal normal serum levels.

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status.

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = -0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = -0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = -0.28, p = 0.06; r = -0.25, p = 0.09 and r = -0.25, p = 0.09, respectively). There is evidence of a possible influence of the -308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.

Anti-apolipoprotein A-1 autoantibodies as risk biomarker for cardiovascular diseases in type 2 diabetes mellitus.

OBJECTIVE: Anti-Apolipoprotein A-1 autoantibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high thrombotic events. The aim of this work is to investigate the incidence of anti-apoA-1 autoantibodies in type 2 diabetes (T2DM) patients with and without CVD and to study potential association with disease risk and its effect on plasma lipid parameters. METHODS: Qualitative determination of anti-apoA-1 IgG was assayed in sera from 302 subjects classified into T2DM patients (n=102), T2DM+CVD (n=112) and healthy controls (n=88). RESULTS: The incidence of anti-apoA-1 IgG was significantly higher among CVD patients (35.7%) than T2DM patients (8.8%) or control subjects (6.1%), p<0.0001. A significant association with CVD was identified (p<0.0001) and subjects who were positive for anti-apoA-1 IgG were at 8.5 times increased risk to develop CVD when compared to controls. Diabetic patients who were positive for the antibodies showed 5.7 times increased CVD risk. ROC analysis indicated anti-apoA-1 IgG as a risk biomarker for CVD in T2DM patients with an AUC value of 0.76, sensitivity of 35.7% and specificity of 91.2%. Studying the effect on lipid parameters, anti-apoA-1 IgG associated with significantly higher serum concentrations of TC and non-HDL-C in all groups and with higher concentrations of LDL-C in diabetic patients and higher TC/HDL-C ratio in CVD patients. CONCLUSION: Our results indicate that anti-apoA-1 IgG is a cardiovascular risk biomarker in T2DM patients.

Is Neck Circumference an Indicator for Metabolic Complication of Childhood Obesity?

BACKGROUND: The possible role of neck circumference (NC) for screening childhood obesity and its complication is not well characterized. AIM: To assess NC and to explore its increase as risk factor with metabolic syndrome (MS) variables. METHODS: Cross sectional case-control study included 50 obese children (BMI ≥95(th) percentile) and 50 healthy (BMI 15(th)-<85(th) percentile). All were subjected to clinical examination, measuring blood pressure (BP), body weight, height, NC, waist (WC) and hip (HC)., fasting blood glucose, insulin and lipid profile. RESULTS: MS was detected among 52% of obese participants, but not among controls (0%). Clinical parameters and most of the laboratory values were higher in subjects with MS than in non-metabolic subjects, with statistical significance only in blood pressure and triglycerides. Among obese without MS, NC showed significantly positive correlations with age, weight, height, WC, HC and negative with LDL. While among Obese with MS, NC showed significantly positive correlations with age, weight, height, BMI-SDS, WC, HC and DBP. CONCLUSION: NC can be considered as a good indicator and predictor for obesity, especially central obesity. However, NC has no relation with lipid profile or fasting blood sugar.

Apolipoprotein B polymorphism distribution among a sample of obese Egyptian females with visceral obesity and its influence on lipid profile.

BACKGROUND: Regional distribution of adipose tissue is more important than total amount of body fat in predicting complications associated with obesity. Apolipoprotein B (Apo B) plays a central role in lipid metabolism. AIM: To investigate the importance of the XbaI polymorphism of Apo B gene (C7673T) as risk factor for visceral obesity and its influence on lipid profile. SUBJECTS AND METHODS: Total of 122 obese adult females (BMI â©¾ 30 kg/m2): 56 of them with visceral obesity (⩾7 cm by abdominal Ultrasound) and 66 without visceral obesity and 36 age matched non-obese (BMI â©½ 25 kg/m2) without visceral obesity were studied. Anthropometric assessment, body composition, visceral obesity and lipid profile evaluation were attempted. Genetic analysis of Apo B XbaI was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Visceral obesity was associated significantly with the presence of the heterozygous (CT) genotype of the XbaI Apo B gene (p < 0.001). Frequency of homozygous (CC) was significantly the least genotype found in females with visceral obesity, while homozygote (TT) genotype was more frequent in those without visceral obesity. T allele (about 70%) was more frequent than C allele (about 30%) in all groups. Significant lowest values of visceral obesity, triglyceride and HDL-C were associated with the presence of (CC) genotype and the highest values were associated with the presence of the heterozygous (CT) genotype; except HDL-C with (TT) genotype. CONCLUSIONS: Study reveals considerable association of Apo B XbaI gene polymorphism with visceral obesity and some lipid profile parameters (TG and HDL-C) among Egyptian females.

Serum cystatin C and tubular urinary enzymes as biomarkers of renal dysfunction in type 2 diabetes mellitus.

Renal tubulointerstitium plays an important role in the development and progression of diabetic nephropathy. The aim of this study was to assess serum cystatin C and 2 renal tubular enzymes, neutrophil gelatinase associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG), as screening markers for early renal dysfunction in patients with type 2 diabetes mellitus (T2DM). ROC curve analysis showed that urinary NAG is the most sensitive marker of microalbuminuria and early renal damage with sensitivity of 83.3%, while serum cystatin C was the most sensitive and specific marker of macroalbuminuria and damage progress with sensitivity of 70.8% and specificity of 83.3% versus 70.6% and 83.3% for uNGAL; and 64.7% and 66.7% for NAG, respectively. Our data indicate that urinary NAG is the most sensitive marker for early renal damage in diabetic patients. However, for damage progress, serum cystatin C is the most sensitive and specific marker for follow-up and monitoring renal dysfunction.

Serum cystatin C is a poor biomarker for diagnosing acute kidney injury in critically-ill children.

BACKGROUND: Accurate diagnosis of acute kidney injury (AKI) is problematic especially in critically-ill patients in whom renal function is in an unsteady state. AIM: Our aim was to evaluate the role of serum (S.) cystatin C as an early biomarker of AKI in critically-ill children. SUBJECTS AND METHODS: S. creatinine and S. cystatin C were measured in 32 critically-ill children who were at risk for developing AKI. AKI was defined by both: Risk,-injury,-failure,-loss, and-endstage renal disease (RIFLE) classification and glomerular filtration rate (GFR) <80 ml/min/1.73 m(2). GFR was estimated by both Schwartz formula and S. cystatin C-based equation. RESULTS: S. cystatin C was not statistically higher in AKI patients compared with non-AKI by RIFLE classification (median 1.48 mg/l vs. 1.16 mg/l, P = 0.1) while S. creatinine was significantly higher (median 0.8 mg/dl vs. 0.4 mg/dl, P = 0.001). On estimating GFR by the two equations we found, a lag between rise of S. cystatin C and creatinine denoted by lower GFR by Schwartz formula in four patients, on other hand, six patients had elevated S. cystatin C with low GFR despite normal creatinine and GFR, denoting poor concordance between the two equations and the two markers. The ability of S. creatinine in predicting AKI was superior to S. cystatin with area under the curve (AUC) 0.95 with sensitivity and specificity (100% and 84.6%, respectively) using the RIFLE classification. The same findings were found when using Schwartz formula. CONCLUSION: S. cystatin C is a poor biomarker for diagnosing AKI in critically-ill children.

Elevated serum resistin in juvenile idiopathic arthritis: relation to categories and disease activity.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is one of the more common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity, including physical disability. The aim of the present study was to assess the serum level of resistin in JIA patients and compare its levels according to the categories, clinical manifestations and disease activity. METHODS: Sixty-eight JIA patients and 33 age and sex matched control children were included in the present study. All patients included in this study were subjected to full history taking, clinical examination. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated and Childhood Health Assessment Questionnaire (CHAQ) was used to measure the functional status. Serum resistin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum resistin was significantly higher in the JIA patients (4.01 ± 2.46 ng/ml) compared to the control (2.08 ± 1.23 ng/ml) (p<0.001) especially those with systemic-onset. Its level was significantly higher in those receiving steroids and those with a positive antinuclear antibody. Resistin significantly correlated with the JADAS27 (r 0.26, p 0.035) and CHAQ (r 0.4, p 0.001). The JIA patients were 50 females and 18 males; however, the level of resistin was insignificantly different according to the gender although there was a tendency to be higher in females. CONCLUSION: Our results reinforce the proposition of an important role for resistin in JIA and may be considered an interesting biomarker for disease activity especially those with systemic onset.

Elevated BAFF (BLyS) and APRIL in Juvenile idiopathic arthritis patients: relation to clinical manifestations and disease activity.

OBJECTIVE: To assess the level of B-cell activating factor belonging to the tumor necrosis factor family (BAFF) also known as B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL) in the serum of Juvenile idiopathic arthritis (JIA) patients and to detect their relation to the clinical manifestations and disease activity in the different subtypes of the disease. METHODS: Seventy-four consecutively recruited JIA patients were clinically examined, the Juvenile arthritis disease activity score in 27 joints (JADAS-27) calculated and Childhood Health Assessment Questionnaire (CHAQ) used to measure the functional status. Thirty-four healthy matched children served as controls. Routine laboratory examinations were recorded and serum BAFF and April were determined. RESULTS: The JIA patients were 20 systemic-onset, 31 oligoarticular and 23 polyarticular. Serum BAFF and APRIL were elevated in JIA patients being higher in systemic onset and both significantly correlated. APRIL significantly correlated with both JADAS-27 and CHAQ scores while BAFF correlated only with JADAS-27. The APRIL serum levels were significantly associated with the presence of RF and ANA. The BAFF serum levels were significantly higher in oligoarticular onset JIA patients with uveitis compared to those without. CONCLUSION: Our results suggest increased BAFF and APRIL serum levels in JIA patients denoting their possible role in the disease and calling for additional research to elucidate the intrinsic mechanisms explaining APRIL and BAFF over expression.

The potential role of insulin-like growth factor 1, insulin-like growth factor binding protein 3 and bone mineral density in patients with chronic hepatitis C virus in Cairo, Egypt.

Insulin-like growth factor 1 (IGF-1) levels have been found to correlate with measurements of bone mineral density (BMD) in liver diseases. This study investigated the relationship between IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and BMD in patients with chronic hepatitis C virus. This study was conducted for 30 patients with chronic hepatitis C virus infection (16 patients without and 14 patients with cirrhosis) and 11 healthy controls. Serum levels of IGF-1 and IGFBP-3 and BMD of the proximal femur and lumbar spine were measured in all subjects. Osteoporosis of the proximal femur and lumbar spine was found in 42.9% and 21.4%, respectively, of the patients with cirrhosis. Patients with liver cirrhosis and osteoporosis of the proximal femur and lumbar spine had lower IGF-1 (P<0.001, P=0.04, P=0.04 respectively). BMD of the proximal femur was lower in cirrhotic patients compared with controls (P<0.01). Patients with liver cirrhosis had lower IGFBP-3 than patients without cirrhosis and controls (P<0.001). Patients with osteoporosis of the proximal femur had lower IGFBP-3 than those without osteoporosis (P<0.01). IGF-1 and IGFBP-3 levels were lower in patients with liver cirrhosis. IGF-1 and IGFBP-3 may play a role in hepatic osteoporosis.