ascorbic-acid and alpha-Thalassemia

The α thalassemia/mental retardation syndrome X-linked (ATRX) mutation impairs DNA damage repair in glioblastoma (GBM), making these cells more susceptible to treatment, which may contribute to the survival advantage in patients with GBM containing ATRX mutations. To better understand the role of ATRX in GBM, genes correlated with ATRX expression were screened in the Cancer Genome Atlas (702 cases) and Chinese Glioma Genome Atlas (325 cases) databases. Sodium-vitamin C cotransporter 2 (SVCT2) was the most positively correlated gene with ATRX expression. ATRX (about 1.99-fold) and SVCT2 (about 2.25-fold) were upregulated in GBM tissues from 40 patients compared with normal brain tissues from 23 subjects. ShSVCT2 transfection did not alter the in vitro viability of GL261 cells. At the same time, it could inhibit the proliferation of GL261 cells in the orthotopic transplantation model with diminished infiltrating macrophages (CD45

Topics: alpha-Thalassemia; Animals; Ascorbic Acid; Brain Neoplasms; Disease Models, Animal; Glioblastoma; Heterografts; Humans; Macrophages; Mental Retardation, X-Linked; Sodium; Sodium-Coupled Vitamin C Transporters; Symporters; X-linked Nuclear Protein

Screening for alpha(0)-thalassemia is usually done using osmotic fragility (OF) test or reduced erythrocyte indexes, both with high sensitivity, but accurate diagnosis requires PCR analysis. However, a low specificity of screening leads to unnecessary PCR workload during a massive population survey. We have established a more effective screening strategy using a combination of three simple tests.. The study was done on 206 subjects with hypochromic microcytosis. Methods include osmotic fragility (OF) test, a dichlorophenolindophenol (DCIP) test for Hb E, a modified Hb H inclusion test, Hb and PCR analyses.. Initial screening with combined OF and DCIP tests identified 9 subjects with negative OF and DCIP tests (-/-), 58 with positive OF test but negative DCIP test (+/-), 13 with negative OF but positive DCIP tests (-/+) and 126 subjects with positive in both tests (+/+). Hb H inclusion was observed in 52 of 206 subjects including 1 in OF/DCIP (-/-), 31 in OF/DCIP (+/-) and 20 in OF/DCIP (+/+) groups. Among these 52 subjects, PCR analysis identified alpha(0)-thalassemia in 28 of 31 (+/-) and 16 of 20 (+/+) groups. Five of 106 subjects with negative Hb H inclusion in the (+/+) group were found to be heterozygous (3 of 5) and homozygous (2 of 5) Hb E co-inherited with alpha(0)-thalassemia.. Hb H inclusion is not an appropriate screening test for alpha(0)-thalassemia in a region where Hb E is common. However performance of the test in the OF/DCIP (+/-) group would enhance the specificity of screening and result in elimination of almost 50% of cases that would have required further PCR confirmation.

Topics: 2,6-Dichloroindophenol; alpha-Thalassemia; Ascorbic Acid; Asia, Southeastern; Carrier State; Erythrocyte Count; Genotype; Hematocrit; Hemoglobin H; Hemoglobins; Humans; Mass Screening; Osmotic Fragility; Thailand

alpha-Thalassaemia is a common red cell disorder in Taiwan, affecting 6-8% of Taiwanese. Previous studies have shown that reactive oxygen species are generated in increased amounts in thalassaemic red cells. This implies the possible alteration of redox status in thalassaemic patients, which may adversely affect their health. In the present study, the redox status of patients with alpha-thalassaemia trait and haemoglobin H (Hb H) disease was investigated. Lipid peroxidation, as measured by the level of plasma thiobarbituric acid reactive substances (TBARS), was increased in alpha-thalassaemic patients, with the highest level of TBARS in Hb H disease patient. The plasma levels of vitamin A, C, and E were significantly lower in alpha-thalassaemic patients than in controls. The overall antioxidant capacity in plasma was inversely correlated with the severity of alpha-globin gene defect: the more severe the form of alpha-thalassaemia, the lower the overall antioxidant capacity in plasma. Erythrocytes isolated from alpha-thalassaemia patients had lower levels of vitamin E, glutathione, catalase and superoxide dismutase. In addition, these alpha-thalassaemic red cells were more susceptible to hydrogen peroxide-induced lipid peroxidation and decrease in deformability. All these data suggest that the alpha-thalassaemic patients suffer from increased oxidative stress and antioxidant deficit, which may complicate the pathophysiology of alpha-thalassaemia.

Topics: Adult; alpha-Thalassemia; Analysis of Variance; Antioxidants; Ascorbic Acid; Case-Control Studies; Catalase; Disease Susceptibility; Erythrocyte Deformability; Erythrocytes; Female; Glutathione; Hemoglobin H; Humans; Lipid Peroxidation; Male; Oxidative Stress; Superoxide Dismutase; Vitamin A; Vitamin E