UNIPROT:P02794 - FACTA Search

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)

Cardiovascular disease is one of the most important causes of morbidity and mortality in children with end-stage renal failure. Chronic inflammation and malnutrition have been suggested to be risk factors for cardiovascular disease. However, to date, biomarkers of inflammation have not been well studied in children. The aim of this study was to investigate the relation between chronic inflammation and cardiovascular risk factors in children on hemodialysis therapy. Twenty-seven patients on hemodialysis (14 girls, 13 boys) of mean age 15.3 +/- 2.4 years and 20 healthy children (13 girls, 7 boys) of mean age 14.3 +/- 2.7 years were included the study. C-reactive protein (CRP), albumin, prealbumin, transferrin, ferritin, and fibrinogen were measured as the markers of inflammation. The levels of CRP, ferritin, and erythrocyte sedimentation rate among hemodialysis patients were significantly higher than those of control subjects (P < .001 for all). Albumin and transferrin levels were found to be lower than those of control group (P = .02 and P < .001, respectively). CRP levels were negatively correlated with albumin, prealbumin, apoprotein A1, HDL, and hemoglobin levels, and positively correlated with erythropoietin/Htc ratios. This study suggests that hemodialyzed children are exposed to chronic inflammation. In addition, CRP may be an indicator of chronic inflammation related to cardiovascular risk factors, such as malnutrition, dyslipidemia, and anemia. In conclusion, we suggest that the risk of cardiovascular disease could be reduced by defining markers of chronic inflammation and malnutrition in hemodialyzed children and by taking necessary measures at an early stage.
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PMID:Relationship between chronic inflammation and cardiovascular risk factors in children on maintenance hemodialysis. 1621 60

Routine monitoring of body iron stores is an essential component of overall management for the patient on hemodialysis. Adequate iron levels are important for the prevention and treatment of iron-deficiency anemia, which is associated with reduced physical functioning, cardiovascular disease, and poor quality of life. Hemodialysis patients are at especially high risk for iron-deficiency anemia, owing to continuous blood losses and supraphysiologic levels of erythropoiesis driven by recombinant human erythropoietin therapy. Unfortunately, the accurate determination of iron status in these patients can be a challenging task, which is made more difficult by inflammation, infections, and the large number of comorbid conditions that can affect commonly used indices of body iron stores. Despite their limitations, transferrin saturation (TSAT) and serum ferritin remain the cornerstones of iron status assessment. Because these values can be altered by a number of non-iron-related factors, it is necessary to go beyond these measures and draw upon additional sources of information to determine the patient's iron status. Other important factors to consider when assessing the need for iron therapy include evidence of underlying inflammatory processes that may block iron mobilization and distort the standard iron indices, the results of alternative iron indices, and the patient's recent history of iron administration. Frequently, the response to a gram of intravenous (i.v.) iron is a safe and effective way to determine the role of iron deficiency in the anemia of the problematic patient. The chronic inflammatory state associated with malnutrition and clinical or subclinical infections substantially increases the risk of misdiagnosing the patient with iron overload and may place the patient at risk of iron deficiency owing to inappropriate withdrawal of i.v. iron therapy. To avoid the risks of withholding iron therapy, the nephrologist must keep this relationship in mind whenever serum ferritin testing suggests replete iron stores, whereas TSAT testing suggests insufficient iron availability.
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PMID:Iron indices: what do they really mean? 1683 Jun 99

Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cytokine interferon-gamma, which is released by activated T-lymphocytes. Human macrophages are centrally involved in plaque formation, and interferon-gamma and macrophages are also of importance in the development of oxidative stress for antimicrobial and antitumoural defence within the cell-mediated immune response. Interferon-gamma also stimulates the enzyme indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine. Again, macrophages are the most important cell type executing this enzyme reaction, but also other cells like dendritic cells, endothelial cells or fibroblasts can contribute to the depletion of tryptophan. Likewise, enhanced tryptophan degradation was reported in patients with coronary heart disease and was found to correlate with enhanced neopterin formation. In chronic diseases such as in cardiovascular disease, biochemical reactions induced by interferon-gamma may have detrimental consequences for host cells. In concert with other pro-inflammatory cytokines, interferon-gamma is the most important trigger for the formation and release of reactive oxygen species (ROS). Chronic ROS-production leads to the depletion of antioxidants like vitamin C and E and glutathione, with a consequence that oxidative stress develop. Oxidative stress plays a major role in the atherogenesis and progression of cardiovascular disease, and it may also account for the irreversible oxidation of other oxidation-sensitive substances like B-vitamins (e.g. folic acid and B12). They are essential cofactors in homocysteine-methionine metabolism. Associations between moderate hyperhomocysteinaemia and cellular immune activation are found in several diseases including coronary heart disease, and data indicate that hyperhomocysteinaemia may develop as a consequence of immune activation. Homocysteine accumulation in the blood is established as an independent risk factor for cardiovascular disease. Homocysteine itself has the capacity to further enhance oxidative stress. Interferon-gamma appears to be a central player in atherogenesis and in the development and progression of cardiovascular disease. Anti-inflammatory and immunosuppressive treatment (e.g. with non-steroidal anti-inflammatory drugs or statins) may among other consequences, also contribute to a slow-down of the adverse effects of interferon-gamma.
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PMID:Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease. 1684 38

Several studies showed that carotid atherosclerosis and stiffness are independent prognostic factors of cardiovascular morbidity and mortality in the general population and in end-stage renal disease patients. However, the impact of established risk factors on carotid structural and elastic properties in non-diabetic elderly hemodialysis patients with negative history for cardiovascular disease has not been fully elucidated. In this paper, we investigated the effect of established and potential risk factors on carotid atherosclerosis and stiffness. Thirty stable, non-symptomatic, non-diabetic patients, aged 65-years and older (mean age 71.4+/-4.15, range 65-79) on hemodialysis for more than 6 months, were included. All patients underwent B-mode ultrasonography of common carotid artery estimating intima-media wall thickness and wall-to-lumen ratio bilaterally and checking for the presence of plaques. Carotid elasticity was evaluated by compliance, distensibility, and the incremental elastic modulus (Einc), whereas systemic arterial stiffening was evaluated by the augmentation index provided by tonometry of radial artery. Our results showed that presence of carotid plaques and wall thickening were frequent findings in this population (76% and 73.3%, respectively) and they were positively associated with fibrinogen (P<0.005), diastolic blood pressure (P<0.004), visceral obesity (P<0.001) and bio-intact PTH (i-PTH) (P=0.03). Overall, systemic and carotid stiffness were strongly correlated with hs-CRP (P=0.018), serum ferritin (P=0.02) with age (P=0.03), lipids (P=0.03) and i-PTH (P=0.05). In conclusion, our findings show that stiffening and atherosclerosis in non-symptomatic elderly HD patients are very common and they are related not only to hemodynamic changes (diastolic blood pressure), inflammation (hs-CRP, fibrinogen, ferritin) or metabolic dysfunction (increased i-PTH, abnormal lipid profile), but also to abnormal fat deposition (increased waist to hip ratio and waist circumference). Considering the high morbidity and mortality of elderly patients, close monitoring of these parameters could be useful to prevent cardiovascular events.
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PMID:Atherosclerotic risk factors and carotid stiffness in elderly asymptomatic HD patients. 1708 15

Anemia is a frequent complication of chronic kidney disease (CKD). Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells (RBCs). Anemia of CKD develops early and worsens with progressive renal insufficiency. Although over 40% of patients with CKD are anemic, anemia in this population is under-recognized and undertreated. Of considerable importance, anemia is a risk factor for cardiovascular disease and is associated with higher rates of hospitalization and mortality. Despite the availability of erythropoiesis-stimulating proteins (ESPs) to stimulate RBC production in CKD patients, approximately three fourths of patients initiating dialysis have a hemoglobin <11 g/dL. The recognition of anemia of CKD begins with an estimation of glomerular filtration rate (GFR), which can be far lower than a normal serum creatinine might suggest, especially in the elderly and in those with poor nutrition and muscle mass. If GFR is <60 mL/min/1.73 m(2), hemoglobin should be checked. The anemia is diagnosed when the hemoglobin is <12 g/dL in a man or a postmenopausal woman, or <11 g/dL in a premenopausal woman. The cause of anemia should be investigated in these individuals; this can range from erythropoietin deficiency due to CKD, to deficiency of vitamin B(12) and/or folate, iron deficiency, blood loss, inflammation, malignancy, and aluminum intoxication. After other causes of anemia have been excluded, CKD is the most likely etiology, and it should be treated with an ESP. Currently, epoetin alfa and darbepoetin alfa are the only 2 ESPs approved for use in the United States. Extended dosing of ESP has potential advantages for the patient and may also improve resource utilization. Consequently, both agents have been tested for dosing at extended intervals. Adequate iron stores--defined as transferrin saturation >20% and ferritin >100 mg--as well as ESP administration are needed to produce an appropriate increase in hemoglobin. Poor response to treatment with ESP can be due to many factors, including presence of iron deficiency, inflammation, continued blood loss, and hemoglobinopathy.
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PMID:Practical approach to the diagnosis and treatment of anemia associated with CKD in elderly. 1709 34

The information available in the literature regarding pulmonary hypertension (PH) in peritoneal dialysis (PD) patients is limited. The objective of the present study was to examine the prevalence and characteristics of PH in PD patients. We retrospectively collected the clinical profile, echocardiographic (ECHO) findings, and biochemical data for 36 PD patients for which ECHO findings were available. We compared characteristics between patients with and without PH. We found PH, defined as pulmonary arterial pressure (PAP) > or = 35 mmHg, in 15 patients. The prevalence of PH was 42%. Mean age (+/- standard deviation) of the patients with and without PH was 58 +/- 15 years and 52 +/- 15 years respectively (p = 0.30). Mean PAP of the PH patients was 43.8 +/- 9.0 mmHg (range: 35-65 mmHg). Patients with PH had a lower ejection fraction than did patients without PH (46.3% +/- 19.8% vs. 56.5% +/- 11.8% respectively, p = 0.07). Patients with PH also had a higher prevalence of global hypokinesia (60% vs. 29%, p = 0. 059) and dilated left ventricular chamber (53% vs. 19%, p = 0.03). In PH patients, body mass index (24 +/- 4.5 kg/m2 vs. 28 +/- 5.0 kg/m2, p = 0.024), normalized protein catabolic rate (0. 78 +/- 0.21 g/kg vs. 0.95 +/- 0.27 g/kg daily, p = 0.049), and ferritin (226 +/- 210 ng/mL vs. 873 +/- 965 ng/mL, p = 0.005) were significantly lower and lactate dehydrogenase was higher (264 +/- 99 U/L vs. 206 +/- 79 U/L, p = 0.06) than in patients without PH. We observed no significant differences in race or sex, incidence of hypertension or cardiovascular disease, or vitamin D analog use between the two groups of patients. During the study period, 60% of PH patients and 38% of patients without PH died (p = 0.19). Values of PAP correlated directly with serum levels of phosphorus (r = 0.44, p = 0.02), CaxP product (r = 0.40, p = 0.04), and parathyroid hormone (r = 0.42, p = 0.03). Of continuous ambulatory PD and continuous cycling PD patients, 21% and 55% respectively had PH (p = 0. 049). In PD patients, PH is highly prevalent and may be associated with higher mortality risk.
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PMID:Pulmonary hypertension in peritoneal dialysis patients. 1788 18

Chronic kidney disease (CKD) is highly prevalent, with increasing numbers of patients affected by the disease world-wide, and anemia is a common finding in patients with CKD. Anemia impacts negatively on cardiovascular disease, exercise capacity, and quality of life, resulting in significant mortality and morbidity. The aim of this study was to evaluate the levels of ischemia-modified albumin and lactate in patients with established anemia associated with CKD and its correlations with hemoglobin levels. Hematocrit, hemoglobin, iron, ferritin, albumin, creatinine, lactate, and ischemia-modified albumin (IMA) were measured in 17 patients with established anemia associated to CKD and 19 controls by standard methods. The results of hematocrit, hemoglobin, iron, and albumin were lower in the anemia group than in the control group. Ferritin, creatinine, and lactate levels were higher in anemia of the CKD group than the control group. IMA increase in the anemia group (0.8115+/-0.1304 absorbance units [ABSU]) compared to control (0.4951+/-0.0393 ABSU). Significant correlations between IMA and lactate, IMA and hemoglobin, IMA and creatinine, and hemoglobin and lactate were observed. IMA and lactate increase during anemia and this elevation could be associated to hypoxia due to low hemoglobin levels. However, our data suggest that lactate is more sensitive to anemia compared to IMA.
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PMID:Evaluation of ischemia-modified albumin in anemia associated to chronic kidney disease. 1820 May 83

Cardiovascular disease caused by accelerated atherosclerosis is the major determinant of morbidity and mortality in chronic kidney disease patients. Vitamin D and its analogs provide survival benefit for hemodialysis (HD) patients. Vitamin D exerts its effects through the vitamin D receptor (VDR) that is coded for by a gene showing several polymorphisms that, in turn, are associated with a variety of diseases and differential responses to vitamin D. In this study, we evaluated the association between 4 VDR polymorphisms (ie, those identified by the restriction enzymes BsmI, ApaI, TaqI, and FokI) and iron indices (serum iron, transferrin, transferrin saturation, and ferritin) in 88 hemodialysis patients routinely treated with vitamin D. The absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f, respectively. Our results show that in HD patients with transferrin saturation <20%, the F allele was more frequent than in HD patients with transferrin saturation >20% (P = .03). This relationship may provide a link between VDR alleles and iron and nutritional markers, which are highly predictive variables of cardiovascular morbidity and mortality in hemodialysis patients.
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PMID:Iron indices and vitamin D receptor polymorphisms in hemodialysis patients. 1833 45

Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.
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PMID:Relationship between serum nickel and homocysteine concentration in hemodialysis patients. 1846 90

Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups. We examined cardiovascular disease risk factors and iron and liver biomarkers, as well as morbidity and mortality associated with the C282Y and H63D variants of HFE in the Atherosclerosis Risk in Communities (ARIC) study, which is a population-based cohort of nearly 16,000 U.S. white and black men and women who were 45-64 years old at baseline. Subjects were followed for an average of 15 years for death, incident coronary heart disease, stroke, and heart failure, and an average of 8 years for incident diabetes. The prevalence of C282Y homozygosity was 0.42% (45/10,800) in whites, which is similar to other North American population-based studies. C282Y homozygotes had significantly lower mean low-density lipoprotein (LDL) cholesterol and fibrinogen as well as higher mean levels of iron (ferritin, transferrin saturation) and liver biomarkers (alanine aminotransferase, Hepascore) compared with HFE wild-type subjects. Rates of all-cause mortality, cardiovascular disease, and diabetes were similar across HFE genotypes. These prospective, population-based data indicate higher serum iron indices and possible mild liver dysfunction or disease in some C282Y homozygotes, but they provide little evidence that HFE C282Y or H63D mutations are related to all-cause mortality, cardiovascular disease, or diabetes. Reduced LDL in C282Y homozygotes may be because of effects of excess iron on cholesterol metabolism and lipoprotein formation in the liver.
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PMID:HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study. 1859 31

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