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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of the inhibitory effects of chelators (desferrioxamine, EDTA, rutin, phenanthroline and ADP) on the production of oxygen radicals in the Fenton reaction and on lipid peroxidation of rat brain homogenates has been studied. It was found that the inhibitory effects of the chelators correlated well with their abilities to oxidize ferrous ions in solution and brain homogenates. On these grounds, it was concluded that the oxidation of Fe2+ ions inside a ferrous ion-chelator complex is a major mechanism of inhibitory effects of these chelators on free radical processes. It is proposed that this mechanism is also realized during therapeutic treatment with chelators of patients with "free radical" pathologies such as Fanconi anemia, beta-thalassemia and Diamond-Blackfan anemia.
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PMID:Mechanism of inhibitory effects of chelating drugs on lipid peroxidation in rat brain homogenates. 813 55

Thalassemia hemoglobinopathies and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are prevalent in Thailand. We studied the prevalence of these disorders from 1,000 cord bloods collected during 14 months period, using EDTA as anticoagulant. Red blood cell G-6-PD quantitative assay was performed in all male subjects. Nine hundred and eighty five specimens were available for hemoglobin (Hb) typing by starch gel electrophoresis. Further evaluation by cellulose acetate electrophoresis and follow up were made in the cases who had Hb E and/or high level of Hb Bart's. It was found that out of 505 males, 61 cases (12.08%) had G-6-PD deficiency. Among 985 cases studied for Hb typing, 61.92% revealed normal Hb type AF while Hb E was present in 18.68% and Hb Bart's designated alpha-thalassemias were present in 25.18% respectively. Of these 985 cases, 18.78% had low Hb Bart's level ie detectable to 8.2% consistent with alpha-thal2, Hb Constant Spring (CS) or alpha-thal1 trait. Ten cases (1.02%) had high levels of Hb Bart's ranging from 16.1-35% without or with Hb CS and E, and further follow-up revealed homozygous Hb CS, Hb A-E-Bart's, Hb H and Hb H with Hb CS disease. The other 53 cases (5.38%) had low level of Hb Bart's with Hb E consistent with alpha-thalassemia trait with Hb E trait. There were 127 cases (12.89%) who had only Hb E trait and 3 cases (0.3%) who had Hb F and E without Hb A initially.
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PMID:Prevalence of hemoglobin E, alpha-thalassemia and glucose-6-phosphate dehydrogenase deficiency in 1,000 cord bloods studied in Bangkok. 862 22

The present minireview summarizes recent developments in the field of DNA separations by capillary zone electrophoresis (CZE), as developed by our group. Separation of antisense oligonucleotides in sieving liquid polymers in isoelectric buffers is discussed first. It is shown that the use of isoelectric buffers permits very high voltage gradients (up to 1000 V cm-1) with much reduced transit times and increased resolution of all truncated and failed sequences. Oligonucleotides can also be analysed by zone electrophoresis against a stationary pH gradient (typically a pH 6.5-10 range): if injected at the alkaline end, the sample components experience stacking and zone sharpening due to modulation of charge as the oligonucleotides move along the pH gradient. Oligonucleotides having the same length, but differing by one single nucleotide in the chain, can be separated in free solution (i.e. in the absence of a sieving matrix) at strongly acidic pH values (pH 3.0-3.3) where charge differences due to base protonation are maximized. By working in free solution, it has also been possible to measure accurately the free mobility of DNAs, shown to reach a constant value of 3.75 +/- 0.04 10(-4) cm2 V-1 s-1 at 25 degrees C and in Tris-acetate-EDTA buffer, pH 8.3, above a critical length of ca. 400 base pairs. Finally, detection of point mutations in human genomic DNA is proven to be feasible in nonisocratic CZE, by running temperature-programmed CZE. The temperature gradient is activated within the capillary lumen by voltage ramps during the run, by exploiting joule effects. This technique has been proven to work for all point mutants, from low-, to intermediate-, to high-melters and has been applied to a number of point mutants in cystic fibrosis and thalassemia.
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PMID:Recent advances in capillary zone electrophoresis of DNA. 962 82

Presently genetic analyses for thalassemia types require relatively large amounts of heparinized blood (5 to 10 ml), and transport as well as degeneration of these sample is a problem in the developing world. We have developed a new method to simplify this procedure and obtain DNAs from small specimens. As experimental materials, thinly smeared blood on a glass slide or blood filtered with and adhered on polysthylene telephtalate (PST) fibers were used. These materials could be safely stored without interfering with DNA extraction for up to 3 months. The slide materials were digested with proteinase K, and DNA was extracted with Tris-EDTA-phenol:chloroform and precipitated with absolute ethanol. The PST specimens were washed with physiologic saline and treated in the same manner as described above. Products were easily amplified by PCR and digested with restriction endonucleases for beta thalassemia typing as well as for HLA-DQA1 gene typing. Results obtained by this method correlated well with previously reported incidences for thalassemia and HLA-DQA1 types in Thailand. This method can be used in the routine laboratory because it allows for stable and biosafe genetic analyses.
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PMID:Detection of thalassemia genes using smeared blood film or leukocytes adhering to polysthylene fibers. 964 Jun 14

Iron chelating agents are essential for treating iron overload in diseases such as beta-thalassemia and are potentially useful for therapy in non-iron overload conditions, including free radical mediated tissue injury. Deferoxamine (DFO), the only drug available for iron chelation therapy, has a number of disadvantages (e.g., lack of intestinal absorption and high cost). The tridentate chelator pyridoxal isonicotinoyl hydrazone (PIH) has high iron chelation efficacy in vitro and in vivo with high selectivity and affinity for iron. It is relatively non-toxic, economical to synthesize and orally effective. We previously demonstrated that submillimolar levels of PIH and some of its analogues inhibit lipid peroxidation, ascorbate oxidation, 2-deoxyribose degradation, plasmid DNA strand breaks and 5,5-dimethylpyrroline-N-oxide (DMPO) hydroxylation mediated by either Fe(II) plus H(2)O(2) or Fe(III)-EDTA plus ascorbate. To further characterize the mechanism of PIH action, we studied the effects of PIH and some of its analogues on the degradation of 2-deoxyribose induced by Fe(III)-EDTA plus ascorbate. Compared with hydroxyl radical scavengers (DMSO, salicylate and mannitol), PIH was about two orders of magnitude more active in protecting 2-deoxyribose from degradation, which was comparable with some of its analogues and DFO. Competition experiments using two different concentrations of 2-deoxyribose (15 vs. 1.5 mM) revealed that hydroxyl radical scavengers (at 20 or 60 mM) were significantly less effective in preventing degradation of 2-deoxyribose at 15 mM than 2-deoxyribose at 1.5 mM. In contrast, 400 microM PIH was equally effective in preventing degradation of both 15 mM and 1.5 mM 2-deoxyribose. At a fixed Fe(III) concentration, increasing the concentration of ligands (either EDTA or NTA) caused a significant reduction in the protective effect of PIH towards 2-deoxyribose degradation. We also observed that PIH and DFO prevent 2-deoxyribose degradation induced by hypoxanthine, xanthine oxidase and Fe(III)-EDTA. The efficacy of PIH or DFO was inversely related to the EDTA concentration. Taken together, these results indicate that PIH (and its analogues) works by a mechanism different than the hydroxyl radical scavengers. It is likely that PIH removes Fe(III) from the chelates (either Fe(III)-EDTA or Fe(III)-NTA) and forms a Fe(III)-PIH(2) complex that does not catalyze oxyradical formation.
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PMID:The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogues prevent damage to 2-deoxyribose mediated by ferric iron plus ascorbate. 1104 79

Novel 3-hydroxypyridin-4-one containing tridentate ligands were synthesised and their physicochemical properties characterised, including ionisation constants and stoichiometric titration with Fe(III). There is an urgent demand for orally active iron chelators with potential for the treatment of thalassaemia. In principle, tridentate ligands are likely to be more kinetically stable than bidentate molecules, but to date no satisfactory molecules have been identified. Fe(III) stability constants were assessed by competition with the hexadentate ligand EDTA. In all cases no evidence was found for a tridentate mode of iron chelation; instead the ligands behaved as bidentate hydroxypyridinones. As a consequence they provide no advantage over the more simple alkyl hydroxypyridinones.
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PMID:Synthesis and physicochemical assessment of novel 2-substituted 3-hydroxypyridin-4-ones, novel iron chelators. 1190 1

We evaluated the new automated glycohemoglobin analyzer HLC-723G7 (G7) intended for beta-thalassemia diagnosis to determine correlation of hemoglobin (Hb) F and Hb A2 quantitation with the Variant beta-Thalassemia Short Program and to evaluate the performance of the G7 analyzer. Two hundred fifty EDTA blood samples with Hb A, A2, and F by Variant were analyzed for Hb A2 and Hb F by G7 device. Recovery, precision, and interference of the G7 analyzer were studied. The R2 values for Hb A2 and Hb F were 0.963 and 0.640, respectively. Recovery of Hb A2 and Hb F of low and high control samples ranged from 96% to 100% and 91% to 101%, respectively. The coefficients of variation (CVs) of intraassay precision ranged from 1.3% to 3.9% for Hb F and 0.0 to 1.9% for Hb A2. The CVs of interassay precision ranged from 1.9% to 5.6% for Hb F and 2.5% to 3.0% for Hb A2. The CVs for Hb F in both conjugated bilirubin and chyle substance groups were higher than the CVs for Hb A2. This evaluation revealed very good correlation of Hb A2 measurement between the G7 and the Variant devices. The performance evaluation demonstrated good recovery, precision, and low interference of both Hb A2 and Hb F measurements.
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PMID:Evaluation of automated glycohemoglobin analyzer HLC-723G7 beta-thalassemia analysis mode. 1507 Feb 15

Secondary iron overload is found in beta-thalassemia (thal) patients because of increased dietary iron absorption and multiple blood transfusions. Excessive iron catalyzes free-radical generation, leading to oxidative damage and vital organ dysfunction. Non-transferrin-bound iron (NTBI) detected in thalassemic plasma is highly toxic and chelatable. Though used to treat iron overload, desferrioxamine (DFO) and deferiprone (L1) also have adverse effects. Green tea (GT) shows many pharmacological effects, particularly antioxidative and iron-chelating capacities. This study was performed to investigate the ability of GT extracts to reduce plasma NTBI concentration and oxidative stress in vitro. The Fe(3+) was found to bind to GT crude extract and form a complex. Green tea crude extract time- and dose-dependently decreased plasma NTBI concentration and counteracted the increase of oxidative stress in both Fe(2+)-EDTA-treated human plasma and erythrocytes. Green tea is a bifunctional natural product that could be relevant for management of iron overload and oxidative stress.
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PMID:Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload. 1679 56

The hemoglobinopathies affect the blood red cells and are the most common monogenic diseases worldwide. The high frequency and clinical severity of the hemoglobinopathies, make them a major public health problem. We report here an updated review on epidemiologic and molecular data of the hemoglobinopathies in Tunisia. From 1980 to 2005, a screening of hemoglobinopathies was performed on a total of 44299 individuals according to 2 kinds of work: a systematic screening on several populations (24240) from different regions of the country and a cohort of individuals referred to our laboratory for hemoglobinopathies suspicion (20059). Blood was collected in EDTA tubes from the studied individuals to determine the hematological parameters, the hemoglobin electrophoretic data and the iron status. DNA analysis was performed by the usual PCR based-procedures for the molecular defects identification. Systematic surveys allowed us to show an average prevalence of hemoglobinopathy carriers of 4.48% reaching 12.50% in some focus regions. The average frequency of B-thal trait is of 2.21% and that of sickle cell trait is of 1.89%. Hemoglobin screening on newborns has shown a frequency of alpha-thal trait of 5.48%. Oriented studies from our hospital experience allowed us to list more than 2394 major forms. Molecular analysis on beta-thalassemia patients allowed to identify 21 different alleles. The two most frequent mutations (cd39 C-->T and IVS1-110 G-->A) accounted for 70% of the total encountered beta-thal mutations. Among the other mutations, three were described for the first time in the world on Tunisian families. The sickle cell disease is associated with the Benin haplotype in 95% of the studied cases. Concerning alpha-thal mutation, the - alpha37 deletion was the most common. We also note the identification of several rare Hemoglobin variants as well as diverse associated forms of anomalies. Knowledge of epidemiological and molecular data of hemoglobinopathies is fundamental to understand the mechanisms of disease expression and the genotype / phenotype correlations. Furthermore, the distribution of the hemoglobinopathies in the regions allows to orientate efficiently the planning tasks regarding control and prevention of these hereditary diseases.
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PMID:[Hemoglobinopathies in Tunisia. An updated review of the epidemiologic and molecular data]. 1729 92

This study was aimed to analyze the hematologic and molecular biologic characteristics of 14 Wenzhou patients with minor beta-thalassemia, to find out the mutation sites responsible for the disease by detecting sequences of PCR products and to analyze the single nucleotide polymorphism. The peripheral blood of patients was collected intravenously and was anticoagulated with EDTA-K(2); then the templates from blood samples were extracted, the related primers were designed for sequencing the products amplified by PCR; finally mutation sites resulting in beta-thalassemia were found through comparison and analysis of sequences. The results indicated that the C-->T heterozygous mutation occurred at the IVS-2 -654 site in 4 cases; the TTCT deficiency appeared at CD41/42 site in 1 case; in 2 sites existed single nucleotide polymorphisms occurring at the 59th site of exon 1 (T/C, CAT/CAC, His) and IVS-2 nt 665 (T/C). It is concluded that single nucleotide polymorphism of minor beta-thalassemia patients born in Wenzhou had specificity, this study found too kinds of gene mutations which are IVS-2 -654 C-->T heterozygous mutation and CD41/CD42 site-TTCT deficiency.
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PMID:[Analysis of single nucleotide polymorphism in the human beta-globin gene of patients with minor beta-thalassemia from Wenzhou]. 1892 3


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