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)

Deferiprone at a dose of 75 mg/kg/day is not sufficiently effective to maintain iron stores at a level which has been considered safe in all patients with iron overload. Our main aim was to determine the safety of long-term therapy with high-dose (100 mg/kg/day) deferiprone. A secondary aim was to determine the efficacy of this high dose. Twelve thalassemia major patients received deferiprone at a dose of 100 mg/kg/day over 2 years. Transient aspartate aminotransferase increase (8 patients), gastrointestinal discomfort (3 patients) and arthralgia (2 patients) were the most commonly reported side effects. None of the patients discontinued therapy. The mean serum ferritin level fell from 3,901 +/- 3,618 to 1,790 +/- 2,205 microg/l after 2 years (p < 0.05). Five of the 12 patients continued to receive deferiprone for an additional 3 years. No new side effects were encountered. The mean serum ferritin level in this subgroup was initially 2,510 +/- 332 microg/l and dropped to 1,511 +/- 664 microg/l after 5 years (p < 0.05). Liver iron levels at the end of the 2-year study ranged from 1.0 to 30.9 mg/g dry weight, 3 of the patients having levels above 15 mg/g.
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PMID:Safety and effectiveness of 100 mg/kg/day deferiprone in patients with thalassemia major: a two-year study. 1622 77

There is significant upregulation of interleukin-18 (IL-18) expression in viral infectious diseases and in some chronic hepatic diseases, especially (i) hepatitis C virus (HCV) infection, (ii) HCV infection with persistently normal ALT levels (PNAL), and (iii) non-alcoholic fatty liver disease (NAFLD). The aim of this study was a better understanding of the implications of plasma IL-18 levels in the above-mentioned liver diseases. Thirty-four patients with HCV infection, 13 with NAFLD, and 10 controls were enrolled. The HCV-RNA and HCV-genotypes and the serum or plasma levels of IL-18, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase, total cholesterol, triglycerides, alpha(1)-fetoprotein, and ferritin were evaluated. Patients with HCV showed higher levels of IL-18 than the NAFLD patients (p <0.01) and the controls (p <0.005). Patients with NAFLD showed higher values of body mass index and liver disease parameters, compared to HCV-infected subjects or controls. These data confirm previous reports of enhanced expression of IL-18 in patients with HCV and NAFLD, compared to healthy subjects, and suggest that IL-18 is important as a marker of liver diseases.
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PMID:Association between plasma interleukin-18 levels and liver injury in chronic hepatitis C virus infection and non-alcoholic fatty liver disease. 1625 58

A study was conducted to determine the relationship between ferritin and glycosylated isoforms of ferritin and insulin resistance in 69 HIV-infected men receiving HAART. Ferritin levels were significantly correlated with aspartate aminotransferase, alanine aminotransferase, bilirubin and with insulin resistance. The ferritin isoelectric focusing patterns of five insulin-resistant HIV-infected patients under HAART showed large amounts of hyperglycosylated isoforms, which was not found in 56 control subjects and 46 untreated HIV-1-infected patients.
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PMID:Hyperglycosylated ferritin in sera of HIV-1-infected patients treated with highly active antiretroviral therapy. 1643 82

Our objective was to assess the iron indexes of patients with one or more mutations of the HFE gene with a specific interest in studying the effect of the H63D/H63D genotype. Eight hundred twenty subjects who underwent HFE mutational testing for C282Y and H63D mutations were retrospectively identified. Data collected included age, gender, HFE genotype, and values for serum ferritin, iron saturation, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Compared to the Wild/Wild genotype (0.34 +/- 0.17), genotypes H63D/C282Y (0.44 +/- 0.14 P < 0.01), H63D/H63D (0.51 +/- 0.21 P < 0.01), and C282Y/C282Y (0.64 +/- 0.20 P < 0.01) had significantly higher transferrin saturation levels and were independent predictors of higher iron saturation in multivariate regression analysis. Compared to the Wild/Wild genotype, no abnormal HFE genotypes had significantly higher ferritin levels, although the genotype H63D/H63D was an independent predictor of higher serum ferritin (P = 0.02) in regression analysis. There was no significant difference in the proportion of patients with abnormally elevated AST (P = 0.64) or ALT (P = 0.80) between groups. H63D homozygotes have elevated transferrin saturation compared to the Wild genotype, comparable to that of C282Y homozygotes and compound heterozygotes. The clinical significance of this finding is unclear but warrants further study.
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PMID:Individuals homozygous for the H63D mutation have significantly elevated iron indexes. 1661 7

In the present study we used patient data to calculate laboratory-specific indirect reference intervals. These values were compared with reference intervals obtained for a healthy group according to recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine and manufacturer suggestions. Laboratory results (422,919 records) from all subjects of 18-45 years of age over a 1-year period were retrieved from our laboratory information system and indirect reference intervals for 40 common analytes were estimated using a modified Bhattacharya procedure. Indirect reference intervals for most of the biochemical analytes were comparable, with small differences in lower [alkaline phosphatase (ALP) (male), alanine aminotransferase (ALT), creatine kinase, iron (male), total iron-binding capacity, folic acid, calcium (female), lactate dehydrogenase (LDH), lipoprotein (a) [Lp(a)], thyroid-stimulating hormone (TSH), total triiodothyronine (T(3)), direct bilirubin, apolipoprotein A-I (apoA-I), glucose, homocysteine, total cholesterol, ferritin, total protein, ceruloplasmin, sodium, blood urea nitrogen (BUN) and uric acid (female)] and/or upper limits [albumin, ALP (male), amylase, apoA-I, creatine kinase-MB (CK-MB), total iron-binding capacity, phosphorus, glucose, total cholesterol, gamma-glutamyltransferase (gamma-GT), magnesium, total protein, high-density lipoprotein cholesterol (HDL-C), total T(3), ALP (male), ALT, aspartate aminotransferase (AST) (male), direct bilirubin (male), creatine kinase, iron, folic acid (female), Lp(a), uric acid and triglycerides], to the reference intervals determined for healthy subjects in our laboratory. The indirect reference intervals, with the exception of a few parameters (creatinine, direct total bilirubin, calcium, BUN and potassium), were not similar to the reference intervals suggested by the manufacturers. We conclude that laboratory-specific reference intervals can be determined from stored data with a relatively easy and inexpensive method. Indirect reference intervals derived from stored data may be particularly suitable for the evaluation of results for the presenting population.
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PMID:Use of total patient data for indirect estimation of reference intervals for 40 clinical chemical analytes in Turkey. 1677 35

To assess the effects of liver iron overload and fibrosis after treatment with a chelating agent in hepatitis C virus (HCV)-infected thalassemia, from April 1999 to July 2004, 45 patients with thalassemia major (age range 9-33 years, mean 19.3) received daily deferiprone (L1) for 23-60 months (75 mg/kg). The patients were divided into two groups on the basis of their hepatitis status (27 with, 18 without). Their serum was analyzed for alanine aminotransferase (GPT), aspartate aminotransferase (GOT), bilirubin (total/direct), r-glutamyl transpeptidase (r-GT), alkaline phosphatase (Alk-P), and ferritin. Liver iron overload and fibrosis were defined by a senior pathologist. No significant differences were demonstrated in serum levels of GPT, GOT, bilirubin, r-GT, Alk-P or ferritin; comparison was made for each group before and after L1 treatment. Iron scores were 2.3 +/- 0.9 and 2.8 +/- 0.9 for the hepatitis C negative and positive groups, respectively (p = 0.07), with liver fibrosis scores of 1.0 +/- 0.5 and 0.4 +/- 0.52 (p = 0.56). The two scores were not higher for the positive group. There was no evidence of: 1) greater iron overload and fibrosis in the HCV-infected thalassemic patients; 2) L1 inducing progressive hepatic fibrosis or worsening iron overload in HCV-infected thalassemic patients after long-term therapy; 3) further damage to liver cells associated with L1 treatment.
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PMID:Effect of deferiprone on liver iron overload and fibrosis in hepatitis-C-virus-infected thalassemia. 1679 45

Beta-thalassemia/hemoglobin (Hb) E is a hereditary hemolytic anemia with varying degrees of severity. Severely affected patients are treated with blood transfusion and/or splenectomy in order to maintain an optimum level of hemoglobin for normal growth and physical activities. As thrombosis has been observed among splenectomized patients, we have investigated alterations in coagulation and fibrinolysis in beta-thalassemia/Hb E patients. Plasma levels of prothrombin, fibrinogen, factors V, VII, VIII, IX and XI, protein C, protein S, thrombin activatable fibrinolysis inhibitor (TAFI) and prothrombin fragment 1+2 were determined in 61 patients (21 non-severe non-splenectomized, 18 severe non-splenectomized, 22 severe splenectomized) and 28 healthy individuals. Serum levels of D-dimer, ferritin, aspartate transaminase and alanine transaminase were also measured. All severe patients received regular blood transfusion. Prothrombin fragment 1+2 and D-dimer were significantly elevated in splenectomized patients compared to the healthy control subjects, whereas levels of proteins C, protein S, TAFI, fibrinogen, and factors V and VIII in the splenectomized groups were statistically lower than those in control group. There are no statistical differences for the other parameters measured between patients and controls. Coagulation tests showed only significantly reduction in TAFI and factor V and VIII levels in severe splenectomized group in comparison with severe non-splenectomized patients. These results demonstrate the existence of a low grade consumptive coagulopathy among blood-transfused splenectomized patients with severe clinical manifestations, indicating that these patients may have a higher risk for thrombosis than comparable patients with intact spleen.
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PMID:Hemostatic alterations in splenectomized and non-splenectomized patients with beta-thalassemia/hemoglobin E disease. 1738 94

Patients with human granulocytic anaplasmosis present with fever, thrombocytopenia, leukopenia, and an elevated aspartate transaminase level. Clinical and histopathologic features of severe disease suggest macrophage activation. Twenty-nine patients with human granulocytic anaplasmosis had higher ferritin, interleukin-10, interleukin-12 p70, and interferon- gamma levels than did control subjects matched for age and sex; severity correlated with triglyceride, ferritin, and interleukin-12 p70 levels. Several severely affected patients had cases that fulfilled macrophage activation syndrome diagnostic criteria. Macrophage activation and excessive cytokine production may belie tissue injury associated with Ananplasma phagocytophilum infection.
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PMID:Human granulocytic anaplasmosis and macrophage activation. 1757 79

Mitochondria are involved in the development of organ failure in critical care diseases. However, the mechanisms underlying mitochondrial dysfunction are not clear yet. Inducible hemoxygenase (HO-1), a member of the heat shock protein family, is upregulated in critical care diseases and considered to confer cytoprotection against oxidative stress. However, one of the products of HO-1 is Fe2+ which multiplies the damaging potential of reactive oxygen species catalyzing Fenton reaction. The aim of this study was to clarify the relevance of free iron metabolism to the oxidative damage of the liver in endotoxic shock and its impact on mitochondrial function. Endotoxic shock in rats was induced by injection of lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v.). We observed that the pro-inflammatory cytokine TNF-alpha and the liver necrosis marker aspartate aminotransferase were increased in blood, confirming inflammatory response to LPS and damage to liver tissue, respectively. The levels of free iron in the liver were significantly increased at 4 and 8 h after onset of endotoxic shock, which did not coincide with the decrease of transferrin iron levels in the blood, but rather with expression of the inducible form of heme oxygenase (HO-1). The proteins important for sequestering free iron (ferritin) and the export of iron out of the cells (ferroportin) were downregulated facilitating the accumulation of free iron in cells. The temporarily increased concentration of free iron in the liver correlated with the temporary impairment of both mitochondrial function and tissue ATP levels. Addition of exogenous iron ions to mitochondria isolated from control animals resulted in an impairment of mitochondrial respiration similar to that observed in endotoxic shock in vivo. Our data suggest that free iron released by HO-1 causes mitochondrial dysfunction in pathological situations accompanied by endotoxic shock.
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PMID:A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction. 1798 71

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of alcohol abuse worldwide. Non-alcoholic steatohepatitis (NASH) is the most progressive form of NAFLD. The aim of this study was to investigate the role of apolipoprotein E (APOE) polymorphisms in the development of NASH. We analysed 57 NASH patients and 245 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a case-control study. The diagnosis of the patients was based on liver biopsy. The serum levels of glucose, lipids, vitamin B12, folic acid, homocysteine, insulin, total biluribin, total protein, albumin, ferritin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined in all of the subjects. Body mass index (BMI), waist circumference (WC), AST, ALT, fasting blood sugar (FBS), total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, insulin and ferritin levels were significantly higher in the 57 patients with NASH compared with the 245 healthy controls. The APOE epsilon3 allele was overrepresented in the whole group of NASH patients (epsilon3=97.37% in NASH versus 82.45% in controls). The APOE polymorphism was statistically significantly associated with NASH (chi(2)=15.741; p=0.008). The APOE3/3 genotype (odds ratio [OR]=7.941; p=0.000) was strongly associated with increased risk for NASH in all NASH patients. Consequently, the APOE3/3 genotype may play a role in the aetiopathogenesis of NASH.
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PMID:Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis. 1846 45


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