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Backgrounds: Recent advances in post Kidney Transplantation (KT) care, have led to a dramatic improvement in short-term outcomes in order to achieve transplantation tolerance; including the ideal tool for clinical monitoring & new therapeutic line. This study was undertaken to analyze the CD62L in Kidney Transplant Recipients (KTRs) and to investigate its efficacy as a marker of good graft survival. Methods: Fifty pediatric KTRs and 12 healthy controls were included in the study, the frequency of T cell activation markers; CD62L was measured with flow cytometry after renal transplantation. Clinical, laboratory, immunosuppressive therapy data and graft function of transplant recipients were collected and correlated with their CD62L peripheral blood percentage. Results: The circulating CD62L% was significantly more in transplant recipients than controls (44.74% ± 17.45% vs. 33.36% ± 11.54%, p = 0.02). CD 62L% was more frequent in recipients of living related donors (p = 0.05), positively correlated with donor age (p = 0.04, r = -0.29*) and CD 4% (p = 0.000, r = 0.615). CD26L% did not show significant association with acute rejection or chronic rejection (p = 0.432, p = 0.91 respectively) or with graft function (serum creatinine or eGFR, p = 0.086, p = 0.988 respectively) or immunosuppressive medications. Conclusion: Peripheral CD62L% is increased after KT than healthy controls, however, it cannot reflect either clinical (serum creatinine and eGFR) or pathological renal graft injury. CD62L surface marker needs more analysis for its potential diagnostic and therapeutic implications as a Treg cell activation marker.

Background Hepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must. Aims This study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls. Methods This study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls. Results miR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group ( p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis ( p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients ( p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients ( p < 0.001). Conclusion miR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.

Conflicting data are available regarding oral iron therapy in iron deficiency (ID), iron deficiency anemia (IDA) and its relation to DNA damage, oxidative stress and antioxidant markers. Our aim was assessment of DNA damage, oxidative stress and anti-oxidant markers in children with ID and IDA before and after low dose iron therapy. The study was conducted in two stages, first stage was assessment of DNA damage using comet assay, malondialdehyde (MDA) and anti-oxidant enzymes levels (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) & total antioxidant capacity (TAC) in thirty-nine children with IDA, forty-five children with ID without anemia and sixty healthy controls. Second stage was assessment of previous markers together with hematological response following oral therapy with 10 mg/day ferric ammonium citrate for 8 weeks. Before treatment, there was no significant difference between the three groups regarding MDA, GPx, SOD, CAT and TAC. A significant increase was detected in the DNA damage in the 2 groups compared to control (p

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.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.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.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.

BACKGROUND: Hepcidin, a small peptide hormone, is established as the main regulator of iron homeostasis. AIM: To estimate serum hepcidin, ferritin, and hepcidin: ferritin ratio in β-thalassemia patients and to determine the effect of splenectomy and hydroxyurea on serum hepcidin. METHODS: A study was conducted on 30 thalassemia major (βTM), 29 thalassemia intermedia (βTI) and 29 healthy children's controls. Data were collected by patient interviewing where detailed history-taking and thorough clinical examinations were carried out. Serum ferritin and hepcidin were measured by ELISA assay (Bioneovan Co. Ltd Beijing, China). RESULTS: Βeta-thalassemia patients had higher serum ferritin, serum hepcidin and lower Hb and hepcidin: ferritin ratio compared to the controls (p < 0.001, 0.010, 0.001, 0.001) respectively. Β-TM patients had higher mean serum hepcidin and serum ferritin compared to β-TI, with statistically significant difference (P = 0.042, P < 0.001, respectively). Twenty-one patients out of 29 βTI was on hydroxyurea therapy; these patients had significantly lower levels of serum ferritin (P < 0.004) and significantly higher levels of Hb (P < 0.004). Serum ferritin was statistically significantly higher in splenectomized patients P < 0.009. Serum hepcidin level was insignificantly higher in splenectomized patients than non-splenectomized patients (21.6 ± 14.75, 17.76 ± 10.01 ng/mL). Hepcidin showed a significantly positive correlation with hepcidin: ferritin ratio in all studied groups. CONCLUSION: Serum hepcidin was elevated in β-thalassemia children with more evident elevation in βTM patients. Splenectomy played no major role in hepcidin regulation. Knowing that hepcidin in serum has a dynamic and multi-factorial regulation, individual evaluation of serum hepcidin and follow up, e.g. every 6 months could be valuable, and future therapeutic hepcidin agonists could be helpful in management of iron burden in such patient.

IntroductionA role for ficolin (FCN) 2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested. The aim of the study was to evaluate a possible relationship between single nucleotide polymorphisms located at positions -602 and -4 of the FCN2 gene and FCN2 serum levels and risk of development of rheumatic fever (RF) and rheumatic heart disease (RHD).Material and methodsSeventy-seven Caucasian Egyptian patients with RF were recruited with a control group of 43 healthy subjects. DNA was extracted for analysis of the FCN2 gene at positions -602 and -4 and serum protein level was measured by ELISA.ResultsFCN2 AA genotype at the -4 position was more frequently observed in RF and RHD patients, as compared to healthy subjects (p = 0.005 and p = 0.013, respectively); furthermore, the A allele was identified as a possible risk factor for the development of RF (p = 0.023, OR = 1.852, 95% CI: 1.085–3.159). The haplotype –602/–4 G/A, which was associated with low median levels of L-ficolin, was observed more frequently in the RF group when compared to the healthy subjects (74/162, 48.1% vs. 29/420, 33.7%, OR = 1.834, 95% CI: 1·034–3.252, p = 0·038). Low serum ficolin 2 level was associated with ESV and EDV increases. FCN 2 level was significantly lower with AA genotypes than GG+AG genotypes of the -4 position (56.68 ±17.90 vs. 66.05 ±18.79, p = 0.008).ConclusionsPolymorphisms linked to low levels of L-ficolin may render an individual at risk of recurrent and/or severe streptococcal infection. The -4 AA genotype and -602/-4 G/A haplotype are possible risk factors for the development of carditis.

BACKGROUND: Anemia is one of the most common complications in end-stage renal disease (ESRD) patients. Hepcidin is a hormone that regulates iron homeostasis in patients with ESRD. Carnitine deficiency is commonly seen in hemodialysis (HD) patients. AIM: This study aimed to investigate the relationship between hepcidin and inflammatory and other anemia markers in children with ESRD and to evaluate the association of carnitine deficiency with anemia in these patients. SUBJECTS AND METHODS: Thirty pediatric patients with ESRD undergoing HD, and thirty healthy, age- and sex-matched children served as controls were included in the study. Serum levels hepcidin, iron status, high-sensitivity C-reactive protein, and total carnitine were measured. RESULTS: Statistically significant increases in serum levels of hepcidin (100.7 ± 0.99 ng\ml vs. 77.43 ± 0.8 ng\ml, p = 0.000), was found in HD children as compared to healthy controls. Statistically significant increase in serum levels of hs-CRP (3.94 ± 0.19 mg/l vs. 1.36 ± 0.07 mg/l, p = 0.04) was found in HD children as compared to healthy controls. However, serum levels of carnitine (29.59 ± 2.46 μmol/L vs. 36 ± 2.39 μmol/L, p = 0.000) showed statistically significant decreases in HD children as compared to healthy controls positive correlation was found between hepcidin and hs-CRP (r = 0.059, p = 0.042). Furthermore, a positive correlation was present between serum carnitine levels and serum iron levels (r = 0.651, p = 0.042). CONCLUSION: Serum hepcidin may be a more useful biomarker of functional iron deficiency in children on HD. The efficacy of carnitine treatment for children on HD with carnitine deficiency and its effect on anemia needs to be studied.

Klotho G-395-A gene polymorphism may impact children with end-stage renal disease (ESRD). We investigated the relevance of Klotho G-395-A on ESRD development and progression, and its relationship with evolution of cardiovascular complications in pediatric dialysis patients. Fifty-five children with chronic kidney disease (CKD) and seventy healthy children were genotyped for Klotho G-395A. Incidence of GA/AA genotypes and A allele were higher in ESRD patients compared with controls (54.5 vs. 7.1%, P

Background Breast cancer (BC) is the most common cancer among Egyptian women, and its early detection is accompanied with decreased mortality rates. MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression and affect cancer development. The expression level of miRNA-155 is up-regulated in BC and correlates with its invasive properties, offering a great potential as a noninvasive biomarker for BC screening. Objective The aim of this study is to evaluate the role of miRNA-155 as an early diagnostic serum-based biomarker of BC. Patients and methods This study was conducted on 30 patients newly diagnosed with BC and associated 20 healthy women as a control group. Serum level of miRNA-155 was measured for all studied cases using real-time quantitative PCR technique. Results MiRNA-155 expression was up-regulated in serum of patients with BC compared with control group (P

Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period. Thirty-two patients were on maintenance and another 32 completed their chemotherapy. Seventy healthy age-matched and sex-matched children served as controls. They were subjected to clinical assessment, haematological panel investigations and TPMT gene polymorphism for G238C, G460A and A719G alleles assessment using PCRfollowed byRFLP analysis.Although none of the studied patients had themutantTPMTvariant alleles,myelosuppression toxicity in the form of different degree of neutropenia was detected in all patients. As a result of myelosuppression toxicity, most of the patients needed 6-MP dose modification either once (53.1%), twice (15.6%), or ≥ thrice (25.1%) during their maintenance course and 96.9% of the patients required to stop 6-MP for less than a week (62.5%), up to 2 weeks (28.1%), or > 2 weeks (6.3%). Patients also developed infection who mostly (71%) needed hospitalization. None of the studied G238C, G460A and A719G TPMT variant alleles were detected. Infections and febrile neutropenia were common causes of 6-PM dose modification and interruption.

Introduction Fc gamma receptor (FcγR) IIa is considered the most widely distributed of the three classes of Fc receptors, and it expresses an allelic polymorphism. This type of polymorphism may modify the immune response and may be an important factor for some diseases. The aim of the study reported herein was to evaluate the association between the FcγRIIa polymorphism and susceptibility to both end-stage renal disease (ESRD) and acute kidney graft rejection (AR) in children who have undergone renal transplantation. Material and methods The study evaluated 70 children who had undergone transplantation and 60 healthy subjects. AR was observed in 25 children. Results FcγRIIa genotypes and alleles were significantly different between transplantation patients and the control group. The assessment for FcγR of the groups in which AR was present showed that there was only a risk of having an acute rejection in homozygous genotype RR. Conclusions FcγRIIa RR genotype and allele frequency was increased in paediatric renal transplant recipients. The present findings showed that FcγRIIa genotype may be related to ESRD disease susceptibility, and FcγRIIa polymorphisms seemed to affect AR.

Context Gene polymorphisms involved in thiopurine methyltransferase (TPMT) transport, metabolism, or targeting are responsible for the variable drug response and regulates thiopurine therapeutic efficacy and toxicity. Objective To determine the frequency of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL) and its influence on chemotherapy response and toxicity. This may allow identify patients who are at high risk for developing toxicity based on each patient's genetic constitution to individualized drug treatment. Design Paediatric patients with ALL, who were treated with BFM 90 or CCG 1991 standard risk protocol, and who experienced myelosuppression toxicity and required interruption and/or modification of thiopurine chemotherapy were recruited over a one-year period. Seventy healthy age- and sex-matched children served as controls. They subjected to clinical assessment, haematological panel investigations, and TPMT gene polymorphism for G238C, G460A, and A719G alleles assessment using PCR followed by RFLP analysis. Results Sixty-four ALL patients out of 150 who were regularly attending pediatric Hematology/Oncology clinic were recruited. The male: female ratio was 40 (62.5%): 24 (37.5%) and their mean age was 6.16 ± 3.16 years. Their diagnosis was T lineage (27%) and pre-B phenotype (73%). Thirty-two patients were on maintenance and another thirty-two were finished with their chemotherapy. Among the 64 patients and 70 control (288 examined allies), neither the studied leukemic patients nor the controls had the mutant TPMT variant alleles in either homozygous or heterozygous form. Myelosuppression toxicity in form of different degrees of neutropenia was detected in all patients, necessitating 6-MP dose modification for most of patients, either once (53.1%), twice (15.6%), or ≥three times (25.1%) during their maintenance course. Patients required stopping 6-MP for less than a week (62.5%), up to 2 weeks (28.1%), or >2 weeks (6.3%). Patients also developed infection that mostly (71%) necessitated hospitalization. Infections and febrile neutropenia were common causes of 6-MP dose modification and interruption. Conclusions The absence of any allelic variation responsible for the low TPMT activity in the studied leukemic patients, together with the fact that patients experienced signs of myelosuppression toxicity during the course of chemotherapy; would suggest the existence of additional factors in the development of 6-MP cytotoxicity.

Background/aim Iron overload is the main concern in treatment of hemolytic diseases with repeated blood transfusion, especially sickle cell disease (SCD). Hepcidin has appeared as the key iron metabolism regulator. Erythroferrone (ERFE) is postulated to function as the chief erythroid regulator. Transferrin receptor 2 (TfR2) acts as an iron sensor on erythroid cells. Our aim is to evaluate serum levels of hepcidin, ferritin, ERFE, and TfR2 and its correlation with molecular genetic study of hepcidin gene expression for SCD patients Patients and methods Patients: 103 children aged 6–18 years with SCD were recruited from the Pediatric Hematology Clinic at the National Research Center and Abo-Elrish Hospital (Cairo University), and 55 healthy children with matched age and sex served as the control group. Methods: laboratory analysis and enzyme-linked immunosorbent assay tests on patient samples were performed for serum hepcidin, ERFE, ferritin and TfR2, and hepcidin gene expression was performed by quantitative real-time PCR. Results Hepcidin RNA expression level showed significant correlation with the duration of the disease and blood transfusion frequency (r=−0.33, P Conclusion Combination of enzyme-linked immunosorbent assay and molecular studies of hepcidin RNA expression could be a diagnostic marker to be used in conjunction with analytical techniques to detect iron overload in pediatric sickle cell disease.

Background The vitamin D is involved in a wide variety of biological processes including bone metabolism, regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoporosis, diabetes. The aim of study was to evaluate the effect of flaxseed oil on bone homeostasis and whether changes in the levels of the bone formation markers are related to vitamin D receptor (VDR) gene polymorphisms i.e. Bsm1 and Fok1 which have been studied by the restriction fragment length polymorphism (RFLP) technique. Results The study included rats were classified in groups as control, diabetic, diabetic received flaxseed oil in the diet, ovariectomised (ovx), and ovx-diabetic received flaxseed oil in the diet. Insulin growth factor-1 (IGF-1) urinary deoxypyridinoline (DPD), and osteocalcin were increased (1.470 ± 88.1), (160 ± 7.11), (21.25 ± 2.33) respectively in ovx. and have significantly positive correlation (p

Advanced glycation end products (AGEs) have biological properties that may contribute to the mortality of children on hemodialysis (HD). This study examines the relationship of LMW fluorescence AGEs, oxidized LDL (ox-LDL), soluble receptor AGE (sRAGE) as markers of oxidative stress in children with end stage renal disease (ESRD) undergoing HD.Thirty children with ESRD undergoing HD, and 30 healthy, age- and sex-matched children were included. Serum levels of LMW fluorescence AGEs, sRAGE, oxidized LDL (ox-LDL), pre- and post-dialysis urea, high-sensitivity C-reactive protein (hs-CRP), hemoglobin (Hb) and serum albumin (ALB), were measured.Abnormal serum inflammatory changes: elevated levels of LMW AGEs, sRAGE, oxLDL, CRP and urea were exhibited in HD children compared with healthy controls; more so in anemic when compared to non-anemic patients. Significant positive correlation was found between serum levels of AGEs and sRAGE.The low molecular weight form of AGEs is associated with oxidative stress in children receiving chronic HD, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients. LMW AGEs levels showed a negative correlation with sRAGE and both exhibit a significant negative relation to seum urea.

Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (β-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*.Hundred patients with β-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done.Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002).Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with β-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis.GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with β-TM.

Breast cancer remains one of the top threats to women's health. The current lack of tumor markers with desirable sensitivity and specificity is a major obstacle toward the future management of breast cancer. Many studies are directed to reveal the diagnostic and prognostic potentials of circulating miRNAs in breast cancer. In this study, we attempt to evaluate the feasibility and clinical utility of circulating miRNA-21 and let-7 as prognostic biomarkers for breast cancer.Real-time quantitative polymerase chain reaction technique was used. Levels of miRNA-21 and let-7 expression were determined in sera from 125 participants representing 3 different groups. With fold-change analysis, the expression of miRNA-21 and let-7 in the decided groups were assessed.Patients with breast cancer showed significantly higher expression of miRNA-21 compared with controls and other participants with benign breast lesions (P .001). The mean expression levels of serum miRNA-21 was 3.27 ± 2.10-fold in patients with breast cancer. The expression of miRNA let-7 was significantly decreased in patients with breast cancer (2.45 ± 2.20-fold) than the control group and the benign breast lesions group (5.27 ± 3.30-fold and 6.22 ± 4.90-fold, respectively; P .001). Levels of miRNA let-7 expression negatively correlated with development of metastases in patients with breast cancer (P .001).Our study establishes the association between altered levels of miRNA let-7 and metastases risk in patients with breast cancer, implying a role of miRNA let-7 in disease progression and prognosis.

Introduction: Serum procalcitonin (PCT) levels are known to be low in healthy individ­uals in healthy subjects but are increased in patients with a severe bacterial infection. It has not been extensively studied in children with chronic kidney disease (CKD), treated either with hemodialysis (HD) or with renal transplantation. Material and methods: During a 6-month period, blood samples were taken from 102 (55 HD children and 47 renal transplant recipients) children with a strong clinical suspicion of infection. Procalcitonin levels were measured by ELISA. Results: Thirty-four/102 cases had proven infections as defined previously. Children with proven infections had a significantly higher PCT (0.920 ±0.24 ng/ml) than those without (0.456 ±0.53 ng/ml), p = 0.04. The ideal cutoff value derived for serum PCT was 0.5 ng/ml. This threshold value established a sensitivity of 94.1% and a specificity of 87.9%. Conclusions: This study indicates that significantly increased PCT concentration is a promising predictor of systemic bacterial infection in children with CKD, with good sensitivity and specificity. This study proposes that serum PCT is a convenient index of infection in CKD children at a cutoff value of 0.5 ng/ml.

Nitric oxide production is reduced in renal disease, partially due to decreased endothelial nitric oxide production. Evidence indicates that nitric oxide deficiency contributes to cardiovascular events and progression of kidney damage. A polymorphism in intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene is a candidate gene in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in chronic renal failure. A case-control study involved 78 children with chronic kidney disease (CKD) and 30 healthy controls. All participants were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction (PCR). Dialyzed (maintenance hemodialysis) and conservative treatment children had significantly higher frequency of the aa genotype and ecNOS4a allele (P

Polyunsaturated fatty acids (PUFA) are reported to be associated with atherosclerotic and inflammatory diseases because they are the major components of the cytoplasmic membrane and are the precursor fatty acids for prostaglandins and leukotrienes. Aim of this study was to identify PUFA profile (PUFAp) in children with end stage renal disease (ESRD) on hemodialysis (HD). And study its relationship with known cardiovascular and arteriosclerotic risk factors. We examined 44 pediatric HD patients (mean age 11 ± 3.36 years). Plasma lipid profile, plasma fatty acid pattern, serum albumin and hemoglobin were studied in these children. Triglyceride levels were increased in the plasma of ESRD patients compared to the healthy subjects. Plasma PUFA decreased whereas behanic acid (saturated fatty acid) increased in ESRD patients. A lower level of eicosapentaenoic acid was revealed in HD patients with cardiomyopathy (HD-CAD) than those without cardiovascular disease(HD-norm) (0.20 ± 0.01 μ/mL vs. 0.88 ± 0.12 μ/mL, P = 0.01). An inverse correlation was found between the linoleic acid level and serum TG level in children on HD (r = −0.54, P = 0.03). A positive correlation was found between plasma arachidonic acid level and serum albumin (r = 0.86, P = 0.003). A significant positive correlation was revealed between plasma eicosapentaenoic acid concentration and serum hemoglobin level (r = −0.64, P = 0.04). Saturated acid was negatively correlated with serum albumin (r = −0.70, P = 0.03). Children under regular hemodialysis evidence significant abnormalities in serum fatty acid levels together with triglyceride abnormalities, a finding that might be relevant to the risk of cardiovascular disease in this setting.

INTRODUCTION Thalassaemic osteopathy is a multifactorial disorder and limited information exists about bone accrual and bone mineral density (BMD) in prepubertal thalassaemic children. The study aimed to investigate some potential genetic and biochemical bone markers as possible early predictors of BMD variations in children with β-thalassaemia major (TM) before puberty. MATERIAL AND METHODS Thirt-one prepubertal children with β-TM, and 43 matched controls were subjected to BMD assessment by dual energy X-ray absorptiometry (DEXA). Vitamin D receptor (VDR) gene polymorphisms (Bsm1, Fok1) and the biochemical bone markers serum osteocalcin and propeptide I procollagen (CPIP) and urinary deoxypyridinoline (DPD) excretion were assessed. RESULTS Bone mineral density was reduced in 25% of thalassaemics at the spine and 15.4% at the hip region. Significantly higher levels of urinary DPD and lower serum osteocalcin and CPIP levels were found in the studied thalassaemic children compared to controls (p < 0.001). A significant negative correlation was present between BMD in spine and hip and the patients' age (r = -0.6367, p = 0.0002 and r = -0.616, p = 0.00079, respectively). There was a significant reduction in BMD in males compared to females. Reduced BMD was more frequent in male patients with genotypes bb and Ff but not in females. Bone mineral density was not related to the studied biochemical bone markers, mean pre-transfusion haemoglobin or serum ferritin. CONCLUSIONS Routine BMD screening with DEXA is proposed to be a sensitive predictor for early bone changes, particularly at the lumbar spine. DR gene polymorphisms of Bsm1 and Fok1 polymorphisms may be determinants of BMD in Egyptian prepubertal male thalassemics.

This study investigated the level of platelet malondialdehyde (MDA) as a marker of oxidative stress and coenzyme Q10 (CoQ10) as an index of antioxidant capacity in patients with type 2 diabetes mellitus and their relation to glycemic control. The study group consisted of 28 patients with type 2 diabetes mellitus (10 men and 18 women) with mean age of 48 +/- 2 years. Ten healthy individuals, age and sex matched with the patients, were used as a control group. Laboratory investigations in the form of lipid profile, glycosylated hemoglobin, plasma MDA, platelet MDA and plasma CoQ10 were assessed for all patients and controls. The study revealed that plasma and platelet MDA, as a marker of oxidative stress, were significantly higher in diabetic patients than in controls. The level of CoQ10, as antioxidant capacity, was significantly lower in diabetic patients than in controls. There was a negative correlation between plasma CoQ10 concentrations and glycosylated hemoglobin. Type 2 diabetic patients are at increased risk of oxidative stress manifested by increased plasma MDA as well as platelet MDA and decreased CoQ10, and this oxidative stress increases with poor glycemic control.

The present research evaluated the intradialytic and postdialytic changes in platelet factor-4 and beta-thromboglobulin plasma levels by enzyme-linked immunoadsorbent assay method and platelet aggregation by ADP as well as flow cytometric percentage of annexin-V-positive platelets as a measure of phosphatidylserine externalization and ultrastructural examination of platelets in 37 uremic patients on regular hemodialysis and 25 age-matched and sex-matched controls. Platelet factor-4 plasma levels increased, remain consistently high during hemodialysis session (20.24 +/- 3.05 IU/ml after 30 min, P < 0.001 and 23.67 +/- 3.68 IU/ml after 240 min, P < 0.001) and returned to control values (6.10 +/- 1.54 IU/ml) only after 24 h following the end of the session. beta-Thromboglobulin showed a trend similar to that of platelet factor-4. Platelet aggregation by ADP showed reduced function in comparison with controls (69.32 +/- 12.37 versus 91.95 +/- 1.59%, P < 0.001). Flow cytometric percentage of annexin-V-positive platelet was significantly elevated (P < 0.001) in uremic patients when compared with normal controls. Ultrastructural studies of platelets 30 min after starting of dialysis showed degranulation of its granules and at 240 min showed complete degranulation, whereas in the postdialytic phase (12 h after the end of dialysis) refilled alpha-granules started to appear. Positive correlations were found between platelet concentration and platelet factor-4 and beta-thromboglobulin plasma levels during and after dialysis (P < 0.001) and with annexin-V-positive platelets percentage (P < 0.001). In conclusion, activated platelets were found in chronic hemodialysis patients, a finding that may explain why uremic patients often suffer from thrombotic accidents. The platelet activation is associated with exposure of phosphatidylserine on the platelet exterior. Platelet factor-4 and beta-thromboglobulin are released from platelets as a result of a defect in their granules membrane as shown by the electron microscopy, mainly as a consequence of the blood-membrane contact during dialysis, and they return only slowly to control values.

Background: Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) are exposed to oxidative stress associated with an impairment of antioxidant defense and an overproduction of oxidative stress markers. Oxidative stress plays a significant role in the development of inflammation in these patients. Objectives: The high incidence of cardiovascular disease in HD pediatric patients is now well established and the involvement of oxidative stress has been hypothesized. This study focuses on a comparison of plasma total antioxidant capacity (TAC) and lipid peroxidation product and evaluates the relationship between these parameters and high-sensitivity C-reactive protein (hsCRP) in pediatric patients on HD. Subjects and Methods: Plasma TAC, lipid peroxidation products, malondialdehyde (MDA) as well as hsCRP were determined in 30 pediatric patients on HD and in 20 healthy controls (HC). Results: TAC and MDA levels were significantly higher in children on HD than in the HC (p < 0.001). The hsCRP values were also significantly higher in HD patients than in HC (p < 0.001). The percentage of HD pediatric patients with CRP >10 mg/l was 30%. The concentrations of TAC and MDA correlated positively with hsCRP in HD patients (TAC: r = 0.52, p < 0.08; MDA: r = 0.75, p < 0.04), but not in HC. Conclusion: Our study demonstrates an increase in oxidative stress in children on HD and that the susceptibility to oxidative stress is strongly related to the levels of MDA produced in plasma. hsCRP levels are higher in children on HD than in HC and this is indicative of a higher degree of inflammatory activity in the former patients. These profound disturbances in oxidative stress markers may provide an explanation for the cardiovascular complications in HD patients.

Changes in plasma tissue factor (TF)-activated factor VII (FVIIa) and plasma tissue factor pathway inhibitor (TFPI) in type II diabetes mellitus are assessed, vascular complicated and noncomplicated patients compared, and whether these novel hemostatic activity markers predict vascular complications in diabetic patients, improving risk assessment, is determined. Fifty type II diabetic patients and 20 healthy controls (age, sex and body mass matched) underwent medical history and examination, fasting plasma glucose level, glycosylated hemoglobin (HbA1c), lipid profile, hemostatic parameters, plasma TF activity, and TFPI and TF expression on blood monocytes. Mean TF, TF activity, TFPI, and FVIIa significantly increased among hyperlipidemic compared with normolipidemic diabetic patients, and normolipidemic diabetic patients compared with controls. Mean percentage TF-positive monocytes with and without lipopolysaccharide, plasma TF activity, TFPI and FVIIa were significantly higher among complicated than noncomplicated diabetic patients. Mean percentage TF-positive monocytes without and with lipopolysaccharide, plasma TF activity, plasma TFPI and FVIIa were higher among diabetic patients with macrovascular compared with microvascular complications. High significant correlation occurred between HbA1c, triglycerides and percentage TF-positive monocytes with and without lipopolysaccharide stimulation, plasma TF activity and both FVIIa and TFPI. High activity levels of plasma TF and FVIIa with increased circulating TF-positive monocytes occurred in type II diabetic patients, especially with vascular complications. Results reflect high procoagulant activity possibly involved in diabetic vascular complications. Elevated TFPI levels were observed, but were not sufficient to balance high procoagulant activity. Correlation of procoagulant activity markers with HbA1c reinforces the importance of optimal glycemic control in type II diabetes.

Immune thrombocytopenic purpura (ITP) etiology is not clarified. Phospholipid antigen antibodies (aPls) occur in ITP patient sera. We studied predictive values of elevated anti-beta2-glycoprotein I (anti-beta2-GP1) or anticardiolipin antibody (aCl) concentrations for secondary ITP detection, comparing levels with steroid therapy responsiveness in three groups of children and adolescents. Participants' antinuclear antibodies, aCls (IgM, IgG) and anti-beta2-GPI (IgG) were assessed. Significantly higher aCl (IgM), aCl (IgG) and anti-beta2-GPI (IgG) mean concentrations occurred in chronic ITP cases compared with acute or control cases. Of chronic ITP cases, 77.8% showed elevated IgG aCl serum concentrations, and all presented increased IgG anti-beta2-GPI serum levels. Significant positive correlation between increased levels of IgG anti-beta2-GPI and increased IgG aCl serum concentrations was determined; these increased IgG concentrations significantly correlated with steroid therapy resistance. A total of 76.1% of ITP cases had positive aPls (all chronic ITP cases, five acute ITP cases). Elevated aCl or anti-beta2-GPI serum IgG isotype concentrations occurred in all nine splenectomized ITP children with positive aPls (three showed increased IgM aCl levels). Follow-up of the initially studied ITP children (2000-2004) revealed 16.7% developed clinical and laboratory criteria of systemic lupus erythrematosus (one acute ITP in remission, six chronic ITP); elevated IgG aCl serum concentrations were found at study start in these seven cases, and six had increased anti-beta2-GPI. IgG classes of both aCls and anti-beta2-GPI may be determinant cofactors for the developing risk of antiphospholipid syndrome or autoimmune diseases in ITP. Great attention should be paid to both assays as predictors for steroid therapy response.

Nitric oxide is a free radical that is elevated in the plasma of patients with heart failure due to contractile dysfunction. This study examines the relation between plasma NO level and left ventricular (LV) diastolic function and its aetiology in heart failure patients in the pediatric age group. We performed echocardiographic Doppler studies in 47 patients (mean age 6.16 ± 2.8 years; 31 males and 16 females) with congestive heart failure. Left ventricular diastolic dysfunction was classified as either a restrictive (RFP) or non-restrictive filling pattern (non-RFP). Same-day venous total nitrite and nitrate levels were measured by colourimetric assay. Plasma NOx levels were significantly higher in the patient group than in the control group (141 ± 54 µmol/l and 43 ± 4 µmol/l, respectively; p < 0.001). ROC curves found that the cut-off point for plasma NOx levels was 60 µmol/l to differentiate between normal children and patients with heart failure. Patients with RFP showed insignificantly higher levels of plasma NOx than the non-RFP patients (p = n. s.). Only in muscular dystrophy patients, the correlation between plasma NOx levels and LV ejection fractions (r = -0.61; p = 0.06) and LV fractional shortenings (r = -0.64; p = 0.04) was negative. On correlating the plasma NOx levels to the severity of heart failure by multiple linear regression analysis, the pulmonary artery systolic pressure was the only variable independently associated with an elevated plasma NOx level (p = 0.05). Plasma NOx levels are elevated in patients with isolated diastolic heart failure. In addition, in patients with LV systolic failure, the severity of LV diastolic dysfunction determines the amount of NO production. J Clin Basic Cardiol 2006; 9 (online): 23-6.

Considerable progress has been made in the treatment of end-stage renal disease over the past 20 yr. Nonetheless, the dialysis population continues to carry an excess mortality from fatal cardiovascular events [Baylis et al., 2006]. One possible explanation derives from the association of uremia and accelerated atherosclerosis [Tripathi et al., 2008]. The latter may be related to pre-dialysis factors such as preceding arterial hypertension, glucose intolerance, secondary hyperparathyroidism, dyslipidemia, and others. However, dialysis itself may further contribute to atherosclerosis by oxidative stress, cytokine stimulation, and other events inherent to hemodialysis (HD). Endothelial dysfunction has been shown recently to be a major initiating factor in atherosclerosis [Kone et al., 1997]. Endothelial dysfunction is associated primarily with decreased nitric oxide (NO). However, endothelial dysfunction of uremia has received little attention. Among the various factors involved in the deterioration of renal function, changes in the hemodynamic are thought to be important. Nitric oxide (NO), an important endothelium derived relaxing factor, is synthesized in the vascular endothelium by the NO synthase. NO is a potent regulator of intrarenal hemodynamics [Baylis et al., 2006 and Tolins et al., 1990]. At the release site it mediates local vasodilatation, antagonizes platelet aggregation, inhibits vascular smooth muscle cell proliferation and also, regulates some vessel-platelet interactions, limits the oxidation of atherogenic low density lipoproteins and has a vasoprotective effect by scavenging superoxide radicals and suppresses leukocyte adhesion to endothelial vessel wall. Multiple lines of evidence have suggested that NO plays a protective role in various important events during atherogenesis. Reduced NO levels are involved in the pathogenesis of the vascular endothelium due to the loss of its vasodilatory effect [Schmidt et al., 1994]. In the kidney, NO dilates renal blood vessels and modulates renin secretion [Kone et al., 1997 and Tripathi et al., 2008]. An impairment of NO production

Inherited bleeding disorders (IBDs) are caused by quantitative and qualitative alterations of either platelets or plasma proteins involved in coagulation and fibrinolysis. Hemophilias are the most frequent IBDs; however, accumulated data from various studies reported that von Willebrand disease (VWD) is the most common cause of IBD, with an increased incidence of platelet function defects, mostly due to the increased rate of consanguinity in some communities. VWD is an inherited disorder of homeostasis due to quantitative or qualitative defect of von Willebrand factor. Data on its epidemiology and impact in developing countries are limited. The objective of this study was to assess the local prevalence of some IBD and establish the clinical and historical variables that are predictive for those bleeding disorders in pediatrics. The study involved 43 children with various bleeding manifestations and 15 age- and sex-matched controls, recruited from the Pediatrics Hematology Clinic at the National Research Centre, Sausan Mubarek children's hospital in Cairo, Egypt and the King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Hematological profile included platelet counts and function, prothrombin time, partial thromboplastin time, factor VIII antigen and its activity, factor IX antigen and its activity, von Willebrand factor and its activity assayed with multimeric analysis. A total of 12 (27.9%) children had VWD, 11 (25.5%) had hemophilia A, three (7%) had hemophilia B, seven (16.3%) had platelet dysfunction and 10 (23.3%) had bleeding with undiagnosed cause. Two of the VWD cases had type I, three had type II, four had type III and one case appeared to have type IIM and another to have IIB VWD. Bruising and epistaxis were the main symptoms in all children with VWD The majority of platelet dysfunction disorders were diagnosed as Glanzmann's thrombasthenia. VWD and Glanzmann's thrombasthenia should be considered not uncommon causes of IBDs in children in Egypt and Kingdom of Saudi Arabia. Routine hematological screening should be mandatory in children with positive family history of bruising and bleeding as a predictor for IBD.

Aim and Methods We investigated the association between polymorphisms of the angiotensin converting enzyme-1 (ACE-1) and angiotensin II type one receptor (AT1RA1166C) genes and the causation of renal disease in 76 advanced chronic kidney disease (CKD) pediatric patients undergoing maintenance hemodialysis (MHD) or conservative treatment (CT). Serum ACE activity and creatine kinase-MB fraction (CK-MB) were measured in all groups. Left ventricular mass index (LVMI) was calculated according to echocardiographic measurements. Seventy healthy controls were also genotyped. Results The differences of D allele and DI genotype of ACE were found significant between MHD group and the controls (p = 0.0001). ACE-activity and LVMI were higher in MHD, while CK-MB was higher in CT patients than in all other groups. The combined genotype DD v/s ID+II comparison validated that DD genotype was a high risk genotype for hypertension .~89% of the DD CKD patients were found hypertensive in comparison to ~ 61% of patients of non DD genotype(p = 0.02). The MHD group showed an increased frequency of the C allele and CC genotype of the AT1RA1166C polymorphism (P = 0.0001). On multiple linear regression analysis, C-allele was independently associated with hypertension (P = 0.04). Conclusion ACE DD and AT1R A/C genotypes implicated possible roles in the hypertensive state and in renal damage among children with ESRD. This result might be useful in planning therapeutic strategies for individual patients.

Background The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. Methods On seventy eight advanced CKD (stages 4 and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or conservative treatment (CT) the following parameters were studied: body mass index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL-cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and 276. Seventy age-and gender-matched healthy subjects served as control subjects. Results Markedly (P = 0.01) elevated plasma adiponectin levels were observed in CKD patients, especially CT patients, compared to control subjects. The wild type of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and CT patients had significantly higher frequency of the TT genotypes of +276G > T gene (P = 0.04) compared with control subjects. A significant positive correlation was observed between plasma adiponectin and IL6 level, whereas negative correlations were found between adiponectin level, cholesterol, HDL cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6 (P = 0.001) was independently associated with plasma adiponectin levels. The adiponectin gene the 276 GT+TT genotypes were associated with a higher level of adiponectin . Conclusions The present study demonstrated that ADPN is related to several metabolic and inflammatory CV risk factors in a manner consistent with the hypothesis that this protein might have a protective role against these factors. We observed an association between the +276G>T SNP in the adiponectin gene and CKD in children. Genetic variation of +276 gene seemed to have a positive impact on circulating adiponectin levels in CKD patients.