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

The alteration of the oxidant/antioxidant balance may affect the susceptibility of low density lipoproteins (LDL) to oxidation in haemolytic disorders such as thalassemia. Thirty patients affected by beta-thalassemia intermedia were examined, and compared with age-matched healthy controls. The mean amount of vitamin E in the thalassemic LDL was lower than control (p < 0.0001), either when it was calculated on the base of LDL protein (61% decrease) or cholesterol (25% decrease). The LDL resistance to Cu2+-induced oxidation, evaluated as the length of the lag phase before the onset of conjugated diene (CD) lipid hydroperoxide production, was 20% lower than control. Other parameters of LDL susceptibility to oxidation, such as the rate of lipid peroxidation, Rp, and the total amount of conjugated dienes produced, CDmax, were only slightly lower than control, which can be explained by a lower content of peroxidable lipids in the thalassemic LDL. Total LDL cholesterol was 1.08 x 10(3) and 2.07 x 10(3) mol/mol LDL in thalassemic and in control LDL, respectively. The length of the lag phase in thalassemic LDL shows a strongly positive correlation with its vitamin E content (r = 0.732; p < 0.0001). The r2-value of 0.53 provides evidence that more than 50% of the lag phase is determined by vitamin E. Oxidizability of LDL lipids may explain 22-24% of the lag phase, as calculated by the inverse correlation between the length of the lag phase and CDmax (r = -0.474; p = 0.008; r2 = 0.22) and Rp (r = -0.499; p = 0.005; r2 = 0.24). In multiple regression analysis, the lag phase was predictable to 66% by vitamin E plus CDmax, and to 60% by vitamin E plus Rp. Plasma vitamin E was 53% lower in thalassemia patients compared to control and positively correlated with vitamin E in the LDL (r = 0.677; p < 0.0001). None of the correlations above were observed in control subjects. In conclusion, beta-thalassemia is associated with very low levels of vitamin E in plasma and in LDL, a condition that renders these particles more susceptible to in vitro oxidative modification and may account for atherogenesis-related vascular diseases described in thalassemia. The present data on a statistically significant correlation between abnormally low vitamin E and oxidizability of LDL contribute substantially to the hypothesis that vitamin E is a pathophysiologically important determinant of antioxidative protection of LDL.
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PMID:Oxidation resistance of LDL is correlated with vitamin E status in beta-thalassemia intermedia. 962 86

We investigated the amount of both zinc and copper in plasma, erythrocytes and hair in 11 patients with hemoglobin H disease, 59 patients with beta-thalassemia/HbE disease and 20 patients with homozygous beta-thalassemia. Plasma and hair zinc levels were found to be much lower, but erythrocyte zinc levels were higher, in thalassemic patients than in controls. The levels of copper in both plasma and erythrocytes were higher in the patients than in the controls. The mechanism with respect to the increase of the amount of both zinc and copper in erythrocytes was not clear; this result may reflect the impairment of zinc and copper utilization in tissues in the pathogenesis of these thalassemic patients.
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PMID:Zinc and copper status of thalassemic children. 965 19

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.
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PMID:Interaction of antioxidants and their implication in genetic anemia. 1060 86

Caution is called for in providing family planning counseling and contraceptive prescriptions for women with hematological disorders. Iron deficiency anemia is a common problem among women of reproductive age. During menstruation women's need for iron intake is 3 times that of men. Oral contraceptives (OCs) are an appropriate contraceptive choice for iron deficiency anemia patients since OCs are associated with reduced blood loss during menstruation. Most IUDs, and especially unmedicated and copper bearing devices, should not be used by women with iron deficiency anemia. Progestin releasing IUDs tend to increase hemoglobin and serum ferritin levels, therefore, patients with iron deficiency anemia may benefit from progestin releasing IUD insertions. Women with hemorrhagic disorders, such as hemophilia, purpuras, and platelet number and function disorders frequently experience menorrhagia. OCs are an appropriate contraceptive for many patients with these disorders. Several studies indicate that patients with hemorrhagic disorders frequently experience reduced bleeding problems when they use OCs. IUDs are contraindicated for women with hemorrhagic diseases because IUDs may increase blood loss. Women with sickle cell hemoglobinopathies need careful counseling. Pregnancy for these women entails high morbidity and mortality risks. Series data shows that pregnant women with sickle cell hemoglobinopathies have a 4%-100% risk of maternal morbidity and a 1%-35% risk of maternal mortality. The risk of maternal morbidity and mortality is equally high for women with hemoglogin sickle cell disease but somewhat lower for women with sickle cell thalassemia. Women with these diseases should be informed about the risks associated with pregnancy. These patients may want to consider sterilization. Oral and IUD contraceptives are contraindicated for patients with these disorders; the former, because it may have a thromboembolic effect, and the latter, because it is associated with high blood loss. There are some reports that progesterone protects against sickling, but more intensive studies must be undertaken before progesterone can be recommended for women with sickle cess disorders. If patients insist on using an OC, a minipill may be prescribed. Barrier methods are probably the best choice for sickle cell disorder patients.
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PMID:Patients with hematologic disorders need careful birth control counseling. 1226 20

ABSTRACT : BACKGROUND : The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS : Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS : Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 +/- 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION : High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.
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PMID:Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. 1291 70

There have been several new developments in the treatment of iron and copper overload disorders, such as haemochromatosis, thalassaemia and Wilson's disease. Clinical trials of orally administered iron chelators, both as monotherapy and in combination with deferoxamine, are in progress around the world. Several new chelators are now being introduced in clinical trials. Future therapies for iron overload may comprise of oral iron binding agents capable of preventing dietary iron absorption from the diet. The characterisation of specific iron transporters such as the divalent metallic transporter and ferroportin may hold promise for the development of 'smart' compounds capable of blocking iron transport. Several new agents are now available for the management of Wilson's disease, including trientine, zinc and tetrathiomolybdate. This review, will discuss the pathogenesis, and current and future therapies for iron and copper overload disorders.
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PMID:Current and future therapy in haemochromatosis and Wilson's disease. 1464 Sep 23

Repeated blood transfusions in patients with thalassaemia subject them to peroxidative tissue injury by secondary iron overload. To study the relationship between iron overload and antioxidant micronutrient status among children with thalassaemia, we measured serum levels of vitamins A and E, zinc, selenium, and copper in 64 children with beta-thalassaemia major and 63 age- and sex-matched controls. All of these elements were significantly lower in the thalassaemic children compared with controls. There was a highly significant inverse correlation between serum ferritin and serum retinol levels, and significant inverse correlations between serum iron and retinol and between serum iron and selenium. Serum ferritin showed a significant positive correlation with duration of chelation and transfusion treatments. Ways are needed to counteract this oxidative damage and its deleterious effect on the prognosis of thalassaemia.
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PMID:Antioxidant micronutrients in children with thalassaemia in Egypt. 1560 29

A serious problem in thalassemia major is growth impairment for which several possible etiologies have been proposed. Sixty-seven patients with thalassemia were randomly enrolled into the study, divided into 2 groups with and without growth failure and the correlation between growth failure and the following parameters was evaluated: age, sex, serum ferritin level, serum zinc and copper concentrations, serum copper-zinc ratio, regularity of blood transfusion, and the regularity and duration of chelation therapy. Among all studied parameters, only age, duration, and type of chelation therapy and age of beginning chelation therapy were significantly different between the 2 groups. Binomial multivariate logistic regression showed that the only significant independent correlation was between age and growth failure. A 1-year increase in age is associated with a 1.57-fold increase in the risk of growth impairment. The results of this study indicated that a temporally cumulative damage to growth-mediating mechanisms except those considered here is responsible for growth failure in thalassemia major.
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PMID:Growth impairment in beta-thalassemia major: the role of trace element deficiency and other potential factors. 1723 59

Here we study the interaction of copper nanoparticles (CuNPs) with different variants of hemoglobin (Hb). The study reports analysis with HbA0 (the major component of human Hb) and HbA2 (a variant that is associated with beta-thalassemia). In the case of HbA0, the major fraction of human Hb, the CuNPs trigger protein aggregation, and this is followed by the precipitation of the protein. The aggregative response is largely attenuated in the case of HbA2. The difference between the two variants is thus amenable to detection by simple optical methods. We verified that CuNPs co-precipitated with specific Hb variants using atomic absorption spectroscopy (AAS) and high-pressure liquid chromatography (HPLC). An associated observation was the reversal of zeta potential of HbA0 induced by the CuNPs (from -11 mV to +13 mV). Dynamic light-scattering (DLS) studies indicated that in the case of HbA0, protein initially broke the nanoclusters into smaller sizes (4 nm), and this was followed by a gradual increase in cluster size. Assays of heme peroxidase activity indicated that the protein unfolded during the process. It is suggested that interaction between the CuNPs and HbA0 stimulates the molten-globule state of the protein, leading to the onset of such an aggregative pathway. When studied for other variants, HbE, a common mutant of Hb, showed similar aggregative behavior, and on the other hand, rare variants such as HbC tended to remain in solution. A suitable scaling up of the approach may have important implications in screening hemoglobinopathies such as beta-thalassemia.
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PMID:Interaction of hemoglobin and copper nanoparticles: implications in hemoglobinopathy. 1729 42

Magnetic susceptibility measurements on the liver can quantify iron overload accurately and noninvasively. However, established susceptometer designs, using superconducting quantum interference devices (SQUIDs) that work in liquid helium, have been too expensive for widespread use. This paper presents a less expensive liver susceptometer that works at room temperature. This system uses oscillating magnetic fields, which are produced and detected by copper coils. The coil design cancels the signal from the applied field, eliminating noise from fluctuations of the source-coil current and sensor gain. The coil unit moves toward and away from the patient at 1 Hz, cancelling drifts due to thermal expansion of the coils. Measurements on a water phantom indicated instrumental errors less than 30 microg of iron per gram of wet liver tissue, which is small compared with other errors due to the response of the patient's body. Liver-iron measurements on eight thalassemia patients yielded a correlation coefficient r = 0.98 between the room-temperature susceptometer and an existing SQUID. These results indicate that the fundamental accuracy limits of the room-temperature susceptometer are similar to those of the SQUID.
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PMID:Noninvasive liver-iron measurements with a room-temperature susceptometer. 1739 91


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