Apoptosis deregulation is important for cancer development, chemotherapy response, and prognosis. Survivin and X-linked inhibitor of apoptosis protein (XIAP) are 2 members of the inhibitor of apoptosis proteins family (IAP). We used semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to determine the levels of expression of survivin and XIAP in 30 patients with de novo acute myeloid leukemia (AML) and 20 age- and sex-matched healthy volunteers. Survivin and XIAP overexpression were detected in 36.7% and 43.3% of cases, respectively. Patients with overexpression of either survivin or XIAP showed unfavorable response to chemotherapy in 81.2% and 91.7%, respectively. Also, these cases showed shorter median survival time (30 days) compared to patients with normal expression of either survivin or XIAP (150 days and 180 days). Patients with overexpression of both survivin and XIAP showed unfavorable response to induction therapy in 100% of the patients and the shortest median survival (30 days). These findings suggest that survivin and XIAP may have a role in leukemogenesis and provide prognostic information.

The relationship between chronic hemolysis with subsequent iron overload, inflammation, and premature atherosclerosis has been documented in hemolytic anemias, particularly β-thalassemia. However, no such relationship has been established in sickle cell disease (SCD). We sought to evaluate SCD as a risk factor for early vascular insult by measuring carotid intima-media thickness (CIMT) and plasma chitotriosidase and to assess the role of the latter as a potential quantitative indicator of vascular inflammation and atherogenesis. Thirty SCD pediatric patients (3-18 years) and 30 matched controls were enrolled. Full clinical history, with hematological and biochemical parameters, was evaluated. CIMT and chitotriosidase activity were also assessed for all study participants. CIMT values were significantly higher in SCD patients (median 0.42; range 0.32-0.6 mm) compared to controls (0.36; 0.34-0.45 mm), P = 0.03. CIMT correlated positively with age (r = 0.460, P = 0.011), and total number of vascular incidents necessitating hospital admission (r = 0.439, P = 0.015). Similarly, chitotriosidase activity was significantly higher among SCD patients (median 59.6; range 7.3-512 nmol/ml plasma/h) compared to controls (32.7; 6.8-63.1 nmol/ml plasma/h), P < 0.001, and showed a positive correlation with serum ferritin (r = 0.517, P = 0.003) and CIMT (r = 0.535, P = 0.002). SCD children are at risk of developing premature atherogenic changes. Plasma chitotriosidase and CIMT may represent useful predictors of these changes.

Background: FOXO3a proteins play multiple crucial roles in immune response. FOXO3 inhibits T cell proliferation, induces T cell apoptosis via upregulation of proapoptotic proteins and it suppresses T cell activation preventing autoimmunity. The role of FOXO3a gene in the pathogenesis of bronchial asthma has been studied in few ethnic groups and revealed its implication in asthma pathogenesis. Objectives: The aim of the current study is to detect the association between single nucleotide polymorphism of the FOXO3a gene (rs13217795) and bronchial asthma, atopy and asthma severity in Egyptian children. Methods: The current cross-sectional case-control study was performed on 75 asthmatic children aged 2 to 12 years following up in the pulmonology outpatient clinic in Children's hospital, Cairo University and 75 age and sex matched healthy controls. Candidates were subjected to clinical evaluation in addition to genotyping for the FOXO3a gene polymorphism using PCR-RFLP technique. Results: The highest frequency was for the heterozygous type CT in both cases and controls groups. The genotype frequencies of mutant type TT for cases and controls were 12 % and 16% respectively, and the T allele frequencies were 37.2% in cases and 46.7% in the control group while CC genotype was present in 37.3% of asthmatic patients and 22.6% in the controls and the C allele was detected in 62.8% and 53.3% for cases and controls respectively. No statistically significant differences were observed between asthmatic patients and controls regarding the different genotypes of the FOXO3a gene polymorphism (p=0.161). No significant association was detected between the different genotypes of the FOXO3a gene polymorphism and the atopic status (p=0.536) or the different grades of asthma severity (p= 0.545). Conclusions: The study of FOXO3a gene polymorphism (rs13217795) in asthmatic Egyptian children revealed low frequency of the mutant TT genotype among cases and controls. In the current study, FOXO3a polymorphism has no role in the pathogenesis of asthma or atopy. Moreover, it has no relation to degree of disease severity.

No abstract

No abstract

No abstract

Bleeding phenotype is reported in β-thalassemia patients. However, the underlying etiology remains elusive. We aimed to assess coagulation profile and the platelet aggregation in β-thalassemia children with bleeding diathesis. Fifty β-thalassemia children with a positive bleeding history were recruited. Bleeding phenotype was explored through full history taking and thorough clinical examination. Complete blood count, prothrombin time, international normalized ratio, and platelets aggregometry were performed for children with negative workup. Mucosal bleeding was manifest among most of our patients (96%). Two-third of patients had decreased aggregation with ristocetin (68%), adenine di-phosphate (64%), and arachidonic acid (64%). While half of the patients (48%) had deficient response to epinephrine. Collagen, ristocetin, and arachidonic acid induced aggregation were negatively correlated to frequency of blood transfusion (P=0.021, r=−0.325; P<0.001, r=−0.465; P=0.018, r=−0.333, respectively). Aggregation to collagen and epinephrine demonstrated a negative correlation with age (P=0.04, r=−0.287; P=0.03, r=−0.315). Deferiprone was associated with a deficient response to ristocetin and collagen when compared with deferasirox or no chelation (P=0.021 and 0.006, respectively). Impaired ristocetin response was linked to hydroxyurea (P=0.035). Platelets function defect should be considered in β-thalassemia patients with bleeding symptoms.

Sickle cell disease (SCD) is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and the presence of circulating cell-derived microparticles (MPs). The aim of this work was to study the impact of erythrocyte-derived circulating microparticles (glycophorin A; CD235 positive) on coagulation activation and their probable role in contribution to painful crisis in SCD patients. Peripheral blood samples of 25 SCD patients during painful crisis and in steady state were studied for the presence of erythrocyte-derived MPs using flow cytometry. Estimation of D-dimer level, as a marker of coagulation activation, was done using semiquantitative assay. Thirty-six healthy individuals, age-and sex-matched, were included as a control group. Erythrocyte-derived MPs level was significantly higher in SCD patients during painful crisis compared to control group (p=0.02), but no statistically significant difference was found between erythrocyte-derived MPs level in SCD patients in steady state compared to controls or to SCD patients during painful crisis (p=0.3 and 0.49, respectively). D-dimer level was higher in SCD patients both during crisis and in steady state compared to controls (p<0.001). SCD during painful crisis is associated with increased levels of erythrocytederived MPs and D-dimer which may contribute to the hypercoagulable state observed in such group of patients.