Use of rapid biomarking technique to estimate oxidative stress in course dependent children with sickle cell disease in Saudi Arabia

Sickle cell disease is characterized by a chain of polymerization reactions in the deoxygenated phase, manifesting in debilitating conditions like inflammation, painful vaso-occlusive crisis and disruption of the bodily defense systems. This vaso-occlusion accompanied by cell adhesion and ischemia-reperfusion injury is linked to a vicious pathway resulting in oxidative stress and an enhanced free radical generation. In children with sickle cell disease, the antioxidant defense system is continuously challenged, resulting in a compromised immunity, and a host of complications. An early, easy, and rapid technique to assess the oxidative stress would help in early therapeutic interventions. As prevalence of sickle cell disease is high in Saudi Arabia, the need for early interventions in children with the problem is of dire necessity. Currently hydroxyurea is the only drug of choice administered. We therefore utilized the free oxygen radical transference (FORT), and free oxygen radical defense (FORD) measurements in children with sickle cell disease on hydroxyurea therapy and compared them with patients not taking the drug. Though patients of both the groups exhibited oxidative stress, the values of free radical transference were considerably higher in the group which did not undertake any treatment as compared to those on hydroxyurea therapy. No appreciable changes were noticed in the FORD values representing the antioxidant capacity. Our results show that the technique is feasible for quick measurements of oxidative stress, and intervention with hydroxyurea therapy benefits in decreasing it. Its incorporation in screening practices would help understand the disease stage better. Abbreviations- SCD-sickle cell disease, FORT- free oxygen radical transference, FORD- free oxygen radical defense</jats:p

Prevalence of the Factor V Leiden Mutation Arg534Gln in Western Region of Saudi Arabia: Functional Alteration and Association Study With Different Populations

The rare Gln534 (Factor V Leiden; FVL) allele (1:169,519,049 T&gt;C) is associated with an increased risk of venous thrombosis. The purpose of this study was to measure the prevalence of Factor V Leiden mutation in thrombophilia patients with deep vein thrombosis. Also, we investigated the functional and structural characteristics of this mutation p.(Arg534Gln) to be examined the cumulative impact on venous thrombosis risk as well correlated with different populations by Genome Wide Association Studies (GWAS). A total of 108 patients with idiopathic deep vein thrombosis were examined for Factor V Leiden gene mutation. Our preliminary data show that about 10% of patients were detected with the heterozygous and homozygous form of the Factor V Leiden mutation. An association analysis confirmed that the Factor V SNP variant (rs6025) was highly associated ( P-value 4.91 x10-^ -39) with an increased risk of venous thrombosis. Also, we found that the recognized SNP was important among HapMap populations. Our results indicated that among the 3 populations (Asian, African, and American) studied, this association was highest in the African population based on the r(2) significant threshold ( P-value 5e-190). In addition, this mutation was located at the domain F5/8 type A 2, which can disturb this domain and abolish its function. Because of aspartic acid nearby wild type position as form in the salt bridge due to this discharge will disturb the ionic interaction made by the wild type residue Arg534. This residue was not found to be in contact with other domains of which the function was known. However, contact with other molecules or domains (THPH2: MIM: 188055) were still possible and might be affected by this mutation that may cause thrombophilia due to activated protein C resistance. </jats:p