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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study focuses on the extent of oxidative DNA damage in peripheral blood leukocytes of chronic peritoneal dialysis (CPD) patients. 8-Hydroxy 2'-deoxyguanosine (8-OHdG) contents in peripheral leukocyte DNA were measured by an HPLC-electrochemical detection method in 24 age- and sex-matched healthy subjects, 22 nondialyzed patients with advanced renal failure, and 42 CPD patients. Mean 8-OHdG content was the highest in CPD patients, followed by the nondialyzed patients, and then by the healthy subjects (19.4 versus 11.9 versus 8.3/10(6) dG; ANOVA P < 0.001). In nondialyzed subjects, peripheral leukocyte 8-OHdG contents inversely correlated with renal creatinine clearance (r = -0.772; P < 0.001). Deficiency of blood antioxidants in CPD and nondialyzed patients was expressed by the lower plasma levels of ascorbate, cholesterol-standardized alpha-tocopherol and whole-blood reduced glutathione, and the higher levels of whole-blood oxidized glutathione as compared with healthy subjects (ANOVA P < 0.05). Mean serum ferritin and iron levels and transferrin saturation were higher in the CPD patients than those in the nondialyzed patients and controls (ANOVA P < 0.05). Flow cytometric analyses of intracellular reactive oxygen species production of peripheral leukocytes showed that spontaneous production by granulocytes, as well as phorbol-12-myristate-13-acetate (PMA)-induced production by granulocytes, lymphocytes and monocytes, were the highest from CPD patients, followed by nondialyzed patients, and then by the healthy subjects (ANOVA P < 0.05). Forward stepwise multiple regression disclosed that uremia, PD treatment, spontaneous and PMA-induced reactive oxygen species production in leukocytes, and serum iron were the independent determinants of peripheral leukocyte 8-OHdG content (R(2) = 0.769; P < 0.001). In conclusion, profound increased 8-OHdG levels in peripheral leukocyte DNA occur in the course of chronic renal failure, gradually increase with its progression, and are further exacerbated by PD treatment.
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PMID:Increased oxidative damage to peripheral blood leukocyte DNA in chronic peritoneal dialysis patients. 1196 Oct 20

Numerous pathologies may involve toxic side effects of free heme and heme-derived iron. Deficiency of the heme-catabolizing enzyme, heme oxygenase-1 (HO-1), in both a human patient and transgenic knockout mice leads to an abundance of circulating heme and damage to vascular endothelium. Although heme can be directly cytotoxic, the present investigations examine the possibility that hemoglobin-derived heme and iron might be indirectly toxic through the generation of oxidized forms of low-density lipoprotein (LDL). In support, hemoglobin in plasma, when oxidized to methemoglobin by oxidants such as leukocyte-derived reactive oxygen, causes oxidative modification of LDL. Heme, released from methemoglobin, catalyzes the oxidation of LDL, which in turn induces endothelial cytolysis primarily caused by lipid hydroperoxides. Exposure of endothelium to sublethal concentrations of this oxidized LDL leads to induction of both HO-1 and ferritin. Similar endothelial cytotoxicity was caused by LDL isolated from plasma of an HO-1-deficient child. Spectral analysis of the child's plasma revealed a substantial oxidation of plasma hemoglobin to methemoglobin. Iron accumulated in the HO-1-deficient child's LDL and several independent assays revealed oxidative modification of the LDL. We conclude that hemoglobin, when oxidized in plasma, can be indirectly cytotoxic through the generation of oxidized LDL by released heme and that, in response, the intracellular defense-HO-1 and ferritin-is induced. These results may be relevant to a variety of disorders-such as renal failure associated with intravascular hemolysis, hemorrhagic injury to the central nervous system, and, perhaps, atherogenesis-in which hemoglobin-derived heme may promote the formation of fatty acid hydroperoxides.
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PMID:Pro-oxidant and cytotoxic effects of circulating heme. 1213 Apr 98

Study results on acute phase reactants of renal failure patients are controversial. In this study, we enrolled 39 patients and divided them into 2 groups: acute renal failure (ARF), and chronic renal failure (CRF) patients. As opposed to CRF patients, the patients with ARF had higher serum ferritin levels that were independent of anemia parameters and other acute phase reactants.
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PMID:Importance of serum ferritin levels in patients with renal failure. 1218 11

Anaemia is one of the most common disorders in pregnancy. The most common cause is iron deficiency. Iron deficiency anaemia is relatively easy to diagnose using a serum ferritin of <15 ng/ml. However, because ferritin is an acute phase reactant, the diagnosis of iron deficiency anaemia in hospitalised or ill patients may be difficult, since serum ferritin may be normal or raised, even in the face of iron deficiency. Soluble transferrin receptor assay (STfR) may be useful in these situations because it reflects the degree of iron requirement in relation to supply, and it is not an acute phase reactant. This study was undertaken to detect subclinical anaemia in pregnant women and to correlate STfR assay with the current diagnostic tests for iron deficiency anaemia. One hundred and fifty-three consenting pregnant women seen at the antenatal clinic at King Edward VIII Hospital (KEH) were recruited. Women on haemantinics, who had renal failure, haemoglinopathy and blood transfusion in the past 3 months, were excluded. An ELISA technique was used for the assay of STfR while standard methodology was used for the other biochemical and haematological assays (FBC, urea, creatinine, c reactive protein and iron studies). One hundred and fifty subjects were included in the final analysis. Seventy-two (48%) had varying degrees of iron deficiency anaemia. In 70% (105) of the samples analysed, serum ferritin and STfR agreed on the presence/absence of iron deficiency anaemia. STfR and S:F were 75% and 86% sensitive; 63% and 82% specific, respectively. The calculated positive and negative predictive values are: STfR 64% and 75%; S:F 84% and 87%; Hb 58% and 57%; mean corpuscular volume 91% and 55%, respectively. Ferritin remains the gold standard for the diagnosis of iron deficiency anaemia. However, because ferritin is an acute phase reactant, soluble transferrin receptor assay may be a better test in ill and hospitalised patients where ferritin may be normal or elevated, despite iron deficiency.
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PMID:Soluble transferrin receptors in anaemia of pregnancy. 1252 53

Cardiovascular diseases connected with atherosclerosis are the main factor of morbidity and mortality in patients with end-stage renal failure. Hyperhomocysteinemia is a known and independent risk factor of atherosclerosis, occurring in 85-95% patients treated with hemodialysis. The aim of this study was to analyse relation between plasma level of homocysteine and chosen indicators of atherosclerosis development and also examined retrospectively cardiovascular complications in these patients. The study was carried out in 100 patients on hemodialysis who were divided into two groups: 72 patients with mild (20.74 mumol/l +/- 3.75) and 28 patients with moderate hyperhomocysteinemia (38.81 mumol/l +/- 9.81). Ultrasonographic examinations of Carotid Communis Artery Intima-Media Thickness (IMT), Ankle-Arm Blood Pressure Index (AABPI), echocardiographic parameters and biochemical examinations such as: PTH, folic acid and Vitamin B12, total protein, albumin, fibrinogen, glucose, total, LDL and HDL cholesterol, transferring, apolipoprotein B, lipoprotein (a), sodium potassium, calcium, phosphate, magnesium, iron, ferritin, urea, creatinine, uric acid and value of Hb, Ht, total iron binding capacity and transferring saturation, were performed. Patients with hypertension were divided into groups according to the number of taken anti-hypertensive drugs. Hyperhomocysteinemia was confirmed in 96% of patients. Frequency and type of acute cardiovascular complications were not related with the level of hyperhomocysteinemia. Statistically significant difference between IMT and level of hyperhomocysteinemia was observed. In patients with mild hyperhomocysteinemia IMT was 0.68 mm +/- 0.24 whereas in patients with moderate hyperhomocysteinemia 0.80 mm +/- 0.25, p < 0.036). Positive correlation between level of homocysteine and IMT (r = 0.22, p < 0.03) was noted. Based on this study, we concluded, that measurement of intima-media thickness is a good indicator of atherosclerosis development and correlates with hyperhomocysteinemia in patients on maintenance hemodialysis. It clearly confirms the role of hyperhomocysteinemia as significant risk factor of atherosclerosis in those patients.
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PMID:[Hyperhomocysteinemia and advancement of atherosclerosis in patients with chronic renal failure on maintenance hemodialysis]. 1273 67

Vitamin E supplementation could elevate circulating vitamin E metabolites while modulating oxidative and inflammatory status in end-stage renal failure patients undergoing hemodialysis. Plasma concentrations of carboxyethyl-hydroxychromanols (alpha- and gamma-CEHC), ascorbic acid, alpha- and gamma-tocopherols, F2-isoprostanes, and inflammatory biomarkers [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP)] were measured in blood samples obtained from patients (n = 11) before and after dialysis on two occasions prior to, and at 1 and 2 mon of daily vitamin E supplementation (400 IU RRR-alpha-tocopherol). Supplementation nearly doubled plasma alpha-tocopherol concentrations (from 18 +/- 0.5 to 31 +/- 1.7 microM, P < 0.0001), whereas gamma-tocopherol concentrations decreased (from 2.8 +/- 0.3 to 1.7 +/- 0.2 microM, P = 0.001). Serum alpha-CEHC increased 10-fold from 68 +/- 3 to 771 +/- 175 nM (P < 0.0001), and gamma-CEHC increased from 837 +/- 164 to 1136 +/- 230 nM (P = 0.008). Vitamin E supplementation also increased postdialysis hematocrits from 38 +/- 1% to 41 +/- 1% (P < 0.001). Dietary antioxidant intakes (vitamins E and C) were low in most subjects; plasma ascorbic acid levels (88 +/- 27 microM) decreased significantly with dialysis (33 +/- 11 microM, P = 0.01). Plasma IL-6, CRP, TNF-alpha, and free F2-isoprostane concentrations were elevated throughout the study. There is a complex relationship between chronic inflammation and oxidative stress that is not mitigated by short-term vitamin E supplementation. Importantly, serum vitamin E metabolite concentrations that increased 10-fold within 30 d of supplementation did not increase further, suggesting routes other than urine for removal of metabolites.
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PMID:Vitamin E supplementation increases circulating vitamin E metabolites tenfold in end-stage renal disease patients. 1457 59

In patients with renal anemia, iron therapy can be administered intermittently or regularly at a low dose. We performed a randomized clinical trial in pediatric patients with end-stage renal failure on hemodialysis and absolute or functional iron deficiency. The study group received maintenance iron therapy according to the ferritin serum levels and the control group received intermittent 10-weekly doses. Success was defined as stabilization of ferritin levels between 100 and 800 microg/l and transferrin saturation (TSAT) between 20% and 50%, in addition to an increase in the hemoglobin level. The major reason for exclusion was iron overload. The study group received 6 mg/kg per month of parenteral iron [95% confidence interval (CI) 3.3-8.8] and the control group 14.4 mg/kg per month (95% CI 12-16.8) ( P<0.001). After 4 months of treatment, ferritin levels increased to 66 microg/l (95% CI 69-200) in the study group and to 334 microg/l (95% CI 145-522) in the control group ( P=0.009). Maintenance therapy and intermittent weekly doses were successful in 73% and 38%, respectively. After 3 months of treatment, hemoglobin levels increased to 10 g/dl, with no difference between the groups. However, in the control group the increase in hemoglobin levels was unsustained, and 3 patients needed transfusion. Patients in the control group had a higher risk of iron overload than patients in the study group (70% vs. 19%). Thus, the regimen based on assessment of serum ferritin levels was more efficient than the intermittent regimen because it increased and maintained the hemoglobin levels with lower iron doses and a lower risk of iron overload.
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PMID:Intermittent versus maintenance iron therapy in children on hemodialysis: a randomized study. 1463 60

Iron therapy maintains iron stores and optimizes the response to recombinant human erythropoietin (r-HuEPO) in patients with end-stage renal failure. Information is limited, however, regarding the preferential route of iron administration in pediatric patients receiving hemodialysis. Therefore, we prospectively randomized 35 iron-replete patients (aged >1 to <20 years) to receive up to 16 weeks of maintenance i.v. ( n=17) or daily oral ( n=18) iron. Eligible patients had received hemodialysis for >2 months, had a baseline transferrin saturation [TSAT] >20%, and were receiving maintenance r-HuEPO. Treatment arms were evenly distributed with respect to baseline demographic and clinical characteristics, with no statistically significant differences in baseline hemoglobin (Hb), hematocrit (Hct), reticulocyte Hb content (CHr), serum ferritin (SF), TSAT, or r-HuEPO dose. In the 35 patients, i.v. iron dextran and not oral iron was associated with a significant increase (138.5 to 259.1 ng/ml, P=0.003) in SF. A comparison of the change in SF between the i.v. iron group and the oral iron group was also significant ( P=0.001). Whereas only i.v. iron was associated with a significant decrease in the dose of r-HuEPO (234.0 to 157.6 U/kg per week, P=0.046) and an increase of the CHr (29.2 to 30.1 pg, P=0.049), these changes were not significantly different from those experienced by patients in the oral iron group. In both groups, the Hct remained stable and in neither group was there a significant change in the TSAT. In summary, although both oral and i.v. iron maintained patients in an iron-replete state in this short-term study, only i.v. therapy allowed for a significant improvement in iron stores.
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PMID:Iron therapy in the pediatric hemodialysis population. 1506 42

Diabetes is known to be a risk factor for the severity of anemia in non-dialyzed patients with renal failure. The aim of this study was to evaluate differences in hemoglobin (Hb) response to erythropoietin (EPO) in diabetic and nondiabetic patients on chronic hemodialysis (CHD). Sixty-four patients on CHD were included in the study: 24 type 2 diabetics (mean age, 59+/-11 years; 10 men, 14 women) and 40 nondiabetics (age, 53+/-14 years; 21 men, 19 women). All patients received a fixed dose of 50 mg ferric saccharate and EPO per week, dosed individually to achieve a target Hb level of 12 g/dl. Hb levels, ferritin, transferrin saturation (TSAT), EPO requirement (IU/kg/week), folic acid, vitamin B12 and C-reactive protein (CRP) were measured every two months. Additionally, the incidence of infectious diseases during the observation period of six months was evaluated, and a univariate correlation analysis of CRP and EPO requirements was performed in both groups. Patients with and without diabetes were divided into two groups each: those with normal CRP and those with elevated CRP. The EPO requirements of these groups were compared. Under identical iron substitution the mean Hb level increased more, but not significantly, in non-diabetic patients than in diabetic patients. After 6 months the mean Hb levels were 12.1+/-1.2 versus 11.5+/-1.2 g/dl (NS), although the actual EPO requirement was higher in diabetic than in non-diabetic subjects (244+/-122 versus 183+/-118 IU/kg/week; p<0.05). CRP after 6 months was significantly higher in diabetic than in non-diabetic patients (2.6+/-2.2 versus 1.5+/-1.3 mg/dl; p<0.05), as was the incidence of infectious disease (n/patient/month) (0.24 versus 0.08; p<0.05). The correlation coefficient between CRP and EPO requirements was statistically significant in both diabetic (r=0.547 p<0.01) and non-diabetic subjects (r=0.577; p<0.001). All other laboratory indices were similar in both groups. In the diabetic patients with normal CRP (n=6) the Hb levels achieved after six months were similar to those of non-diabetic patients (n=10) with normal CRP (11.9+/-1.1 versus 12.1+/-1.2%), and the required EPO was comparable. We conclude that the Hb response to EPO is reduced in diabetic patients on CHD. This elevated EPO requirement may be explained by a greater prevalence of infectious diseases, characterized by a significantly higher CRP level, in these patients. Other causes for the elevated EPO requirement could be excluded.
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PMID:Erythropoietin requirement in patients with type 2 diabetes mellitus on maintenance hemodialysis therapy. 1569 Sep 69

Classic iron deficiency (ID) does not represent a challenge for the laboratory and physicians. The anemia that accompanies infection, inflammation, and cancer, commonly termed anemia of chronic disease (ACD), features apparently normal or increased iron stores. However, 20% of these patients have iron-restricted erythropoiesis (functional ID), an imbalance between the iron requirements of the erythroid marrow and the actual iron supply. Functional ID leads to a reduction in red cell hemoglobiniza-tion, causing hypochromic microcytic anemia. The diagnosis of functional ID in real time is based on measuring the hemoglobin content of reticulocytes. An examination of the biochemical markers of iron metabolism demonstrates weaknesses in the diagnosis of functional ID. We developed a diagnostic plot for the assessment of iron status in ACD and the detection of advancing ID in patients with ID, ACD, and the combined state of functional ID and ACD. The plot indicates the correlation between a marker of the iron supply for erythropoiesis (ie, the ratio of the soluble transferrin receptor value to the logarithm of the ferritin value) and the reticulocyte hemoglobin content and functions as a marker of iron demand. The diagnostic plot shows good selectivity for assessing the iron status of disease-specific anemias such as classic ID, end-stage renal failure, cancer-related anemia, and the anemia of infection and inflammation. The therapeutic implications of the diagnostic plot are to differentiate patients who should be administered oral iron supplements, recombinant human erythropoietin (r-HuEPO), or a combination of r-HuEPO and iron. The response of erythropoiesis to r-HuEPO depends on the iron supply and the proliferation of erythropoiesis. The lack of an increase or a decrease in reticulocyte hemoglobin levels indicates a nonresponder to r-HuEPO or functional ID.
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PMID:Anemia of chronic disease: pathophysiology and laboratory diagnosis. 1579 May 48


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