Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron-chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13-40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1-weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.
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PMID:Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. 158 21

174 serum ferritin assays in 121 patients with various haemolytic disorders have been performed. The mean serum ferritin levels were significantly increased in all these disorders in contrast to healthy controls. The highest serum ferritin levels were found in pyruvate kinase (PK) deficiency, moderate increase was observed in hereditary sphaerocytosis (HS) and in autoimmune haemolytic anaemia (AIHA) with massive haemolysis and in glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Mild elevation of serum ferritin levels was depicted in paroxysmal nocturnal haemoglobinuria (PNH), in beta thalassaemia minor and in other types of haemoglobinopathies. The range of values was associated with a degree of haemolysis and its relation to duration of the disease was not apparent in most cases. Highly significant differences between serum ferritin levels in splenectomized and non-splenectomized patients with HS and between serum ferritin levels in patients with AIHA with massive haemolysis or in remission were found. As compared to normal controls, significant increase of serum ferritin levels was observed even in patients with AIHA in remission or in splenectomized patients with HS. In two patients with PK deficiency the levels exceeding 2,000 micrograms/l indicated manifest iron overload. A reliability of serum ferritin assay as an index of iron stores in haemolytic disorders has been discussed.
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PMID:Serum ferritin in patients with various haemolytic disorders. 169 23

The aim of this study was to determine the crude prevalence of alpha-thalassemia traits in Taiwan. A total of 1435 healthy employees from a statewide company were randomly screened by complete blood count determination with indices. Subjects with mean corpuscular volume less than 80 fl were analyzed by hemoglobin electrophoresis on cellulose acetate to exclude beta-thalassemia and with serum ferritin to exclude iron deficiency. Modified hemoglobin H inclusion staining was performed to confirm the diagnosis of alpha-thalassemia traits, and DNA probe studies were used to confirm the validity of this test. The overall prevalence rate of alpha-thalassemia trait was 3.4% (48 out of 1435). In persons of mainland Chinese origin, prevalence was 0.4%, and among persons of Taiwanese origin, it was 4.0% (47 out of 1171). We conclude that alpha-thalassemia traits are common genetic disorders in Taiwan and that antenatal screening is advised to reduce the frequency of occurrence of hemoglobin Bart's hydrops fetalis. The methods we used proved to be reliable and inexpensive.
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PMID:Alpha-thalassemic traits are common in the Taiwanese population: usefulness of a modified hemoglobin H preparation for prevalence studies. 174 8

To elucidate the effects of iron on lipid peroxidation, three kinds of assays were done. (i) The effects of intravenous injection of single doses of iron dextran (100 mg iron) on lipid peroxidation in various tissues and the blood plasma of rats were examined by the thiobarbituric acid reaction. Malondialdehyde concentrations were significantly elevated in the spleen, heart, and plasma 3 h after injection, whereas significant increases were observed in the liver and adipose tissue at 24 and 48 h, respectively. In the liver and spleen, the elevated malondialdehyde concentrations persisted until Day 28. In contrast, levels were reduced in the heart and adipose tissue within 4 weeks after iron injection. Plasma malondialdehyde concentrations were 70-times that of controls at 24 h after iron injection. The level subsequently decreased sharply by Day 6. In red blood cells, lipid peroxidation was not affected by iron. Malondialdehyde levels were correlated with the iron contents of the liver, spleen, heart, adipose tissue, and plasma (r value range 0.39-0.88, p less than 0.05). Furthermore, there was a strong correlation in the liver and spleen at iron levels below 2,000 micrograms/g (r = 0.94, p less than 0.0001; r = 0.94, p less than 0.0001, respectively). (ii) In vitro experiments demonstrated that the addition of iron as ferric chloride, iron dextran, ferritin, and hemosiderin to normal liver homogenate accelerated malondialdehyde production. However, such increases were less than 10% of those caused by equivalent iron in the liver homogenate of iron treated rats. (iii) Compared to controls, spleens from eight thalassemia patients showed a high level of malondialdehyde and iron.
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PMID:Effects of iron on lipid peroxidation. 174 52

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.
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PMID:[Nuclear magnetic resonance and iron overload in thalassemia]. 179 2

Twenty-four patients with beta thalassaemia major, aged 8-22 years (mean 15.3 +/- 8.1) were given 1-2, dimethyl-3-hydroxypyrid-4-one (L1) orally for a period of three months. The drug was given in the dose of 25 mg/Kg/day for the first week and gradually increased to 100 mg/Kg/day which was continued until 3 months. The mean urinary iron excretion was 5.73 +/- 3.648 mg/day on 25 mg/Kg/day of L1; 15.2 +/- 11.225 mg/day on 50 mg/Kg/day; 24.2 +/- 12.69 mg/day on 75 mg/Kg/day and 36.3 +/- 19.4 mg/day on 100 mg/Kg/day of L1. Serum ferritin estimated by ELISA before and 3 months after L1 therapy in 21 patients showed significant drop in levels, the mean drop being 964.3 +/- 844.4 (P less than 0.001). The only side-effects noted were transient gastrointestinal symptoms in 5 patients and skeletomuscular pain in 3 patients. Both these groups of symptoms were of transient nature. The efficacy of L1 appears to be excellent and equivalent to the standard iron chelation therapy available at present i.e. desferrioxamine. It appears to be free of major toxicity. L1 is also a specific chelator for iron as it does not deplete trace metals. L1 appears to be a cheap and effective oral alternative to desferrioxamine for treating iron overloading.
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PMID:Efficacy and safety of 1-2, dimethyl-3-hydroxypyrid-4-one (L1) as an oral iron chelator in patients of beta thalassaemia major with iron overload. 181 96

This study examined anterior pituitary function and the effect of chelation therapy in 31 patients with beta-thalassemia/HbE disease. Patients were divided into those receiving chelation therapy by deferoxamine and those receiving no such therapy (control group). Pituitary function studies were repeated in both groups 18 months later. The results showed decreased pituitary responses following stimulation in 22 patients. Among these, gonadotropin and PRL responses were most affected. After 18 months, serum ferritin levels had significantly decreased in the deferoxamine group. PRL and GH responses were improved in 3 patients receiving chelation therapy without changes in other hormone responses. In contrast, no changes in pituitary responses were shown in the control group at the end of follow-up. There were 6 drop-outs (4 in the control and 2 in the deferoxamine group) and 3 deaths (2 in the control and 1 in the deferoxamine group) during 18 months. In conclusion, gonadotropin and PRL deficiencies occur most frequently in thalassemic patients. Chelation therapy for 18 months markedly reduced serum ferritin level and might preserve or improve PRL and GH secretions, but seems to have no beneficial effects on other pituitary hormone reserves.
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PMID:Pituitary function in thalassemic patients and the effect of chelation therapy. 190 Mar 79

Single-dose and steady-state pharmacokinetics of the new oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1) were studied in 14 patients with thalassemia and correlated with iron excretion. Food prolongs the rate of absorption of L1, but it does not affect significantly the extent of absorption measured by the area under the plasma concentration-time curve. Similarly, it does not affect the chelation potential of the drug. The mean elimination half-life of the drug is 3 hours, suggesting that a divided dose every 8 hours may assure better chelation. Our steady-state studies reveal that urinary iron excretion is independently influenced by body iron load (measured by ferritin levels) and by steady-state trough concentrations of the drug. While patients were receiving an unchanged regimen of 75 mg/kg/day, we have detected a gradual and significant decrease in trough concentrations in the presence of unchanged patients' compliance monitored by the Medication Event Monitoring System, diaries, and pill count. These findings suggest self-induction of L1 metabolism or decreased absorption during long-term therapy. Because of the concentration-dependent iron excretion, patients may need increasing doses to achieve negative iron balance.
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PMID:Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia. 191 64

The cores of ferritins isolated from different organs of human subjects with beta-thalassemia/hemoglobin E (beta-thal/HbE) disease have different size distributions and crystallinities depending on the source organ. These patients have not been treated by hypertransfusion regimen or iron chelation therapy. beta-Thal/HbE spleens and livers yield ferritin cores which are less crystalline than those isolated from normal spleens and livers, reflecting the more rapid deposition of iron in the diseased state. Ferritins isolated from the hearts and pancreases of beta-thal/HbE subjects were found to have larger, more crystalline cores than those from the beta-thal/HbE livers and spleens, possibly as a consequence of the role of the heart and pancreas as long-term iron deposition sites in this iron overload pathology.
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PMID:Organ-specific crystalline structures of ferritin cores in beta-thalassemia/hemoglobin E. 193 35

Serum ferritin spectrotypes from patients heterozygous for beta-thalassaemia were determined after agarose isoelectric focusing followed by radio-immunofixation with anti-ferritin antibody. Multivariate analysis demonstrated a specific spectrotype for heterozygous beta-thalassaemia. This spectrotype was shown to be different from those in hereditary spherocytosis and idiopathic haemochromatosis. Statistical discrimination reached 100% of well-classified patients between these pathological conditions.
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PMID:Serum ferritin spectrotypes in patients with heterozygous beta-thalassaemia. 204 59


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