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

While the prevalence of iron deficiency has remained relatively constant, there has been continuing refinement in its laboratory recognition, especially with the recent introduction of serum ferritin and FEP measurements. It is helpful to classify iron deficiency into three stages. Storage iron depletion is identified by marrow examination or serum ferritin, iron deficient erythropoiesis by TS, FEP, or MCV, and iron deficiency anemia by hemoglobin concentration or therapeutic iron trial. Combinations of these measurements have been used in prevalence studies to obtain a quantitative measure of body iron stores. The optimal laboratory approach to diagnosing iron deficiency depends on the clinical setting. In the office or outpatient clinic, iron depletion is best recognized by the serum ferritin, although the TS, FEP, and MCV are helpful in gauging its severity. In hospitalized patients with overt anemia, the TS, FEP, and MCV are much less helpful because similar changes are seen in the anemia of chronic disease. Examination of marrow iron remains the method of choice, especially in patients with infection, chronic disease, malignancy, or liver disease, although in many clinical situations the same information can be obtained from a serum ferritin. Serial measurements of serum ferritin have been particularly useful in monitoring patients at high risk of iron deficiency such as those with rheumatoid arthritis, chronic inflammatory bowel disease, or chronic renal failure.
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PMID:Clinical evaluation of iron deficiency. 676 40

Interleukin 11 (IL-11) is a pleiotropic cytokine with biological activities on many different cell types. Recombinant human IL-11 (rhIL-11) is produced by recombinant DNA technology in Escherichia coli. Both in vitro and in vivo, rhIL-11 has shown effects on multiple hematopoietic cell types. Its predominant in vivo hematopoietic activity is the stimulation of peripheral platelet counts in both normal and myelosuppressed animals. This activity is mediated through effects on both early and late progenitor cells to stimulate megakaryocyte differentiation and maturation. rhIL-11 has been approved for the treatment of chemotherapy-induced thrombocytopenia. The hematopoietic effects of rhIL-11 are most likely direct effects on progenitor cells and megakaryocytes in combination with other cytokines or growth factors. rhIL-11 also induces secretion of acute phase proteins (ferritin, haptoglobin, C-reactive protein, and fibrinogen) from the liver. The induction of heme oxidase and inhibition of several P450 oxidases have been reported from in vitro studies. In vivo, rhIL-11 treatment decreases sodium excretion by the kidney by an unknown mechanism and induces hemodilution. rhIL-11 also exhibits anti-inflammatory effects in a variety of animal models of acute and chronic inflammation, including inflammatory bowel disease, inflammatory skin disease, autoimmune joint disease, and various infection-endotoxemia syndromes. rhIL-11 has trophic effects on non-transformed intestinal epithelium under conditions of mucosal damage. The mechanism of the anti-inflammatory activity of rhIL-11 has been extensively studied. rhIL-11 directly affects macrophage and T cell effector function. rhIL-11 inhibits tumor necrosis factor-alpha (TNF alpha), interleukin 1beta (IL-1beta), interleukin 12 (IL-12), interleukin 6 (IL-6), and nitric oxide (NO) production from activated macrophages in vitro. The inhibition of cytokine production was associated with inhibition of nuclear translocation of the transcription factor, nuclear factor kappa B (NF-kappaB). The block to NF-kappaB nuclear translocation correlates with the ability of rhIL-11 to maintain or enhance production of the inhibitors of NF-kappaB, IkappaB-alpha and IkappaB-beta. In addition to effects on macrophages, rhIL-11 also reduces CD4+ T cell production of Th1 cytokines, such as IFN gamma induced by IL-12, while enhancing Th2 cytokine production. rhIL-11 also blocks IFN gamma production in vivo. The molecular effects of rhIL-11 have also been studied in a clinical trial. Molecular analysis of skin biopsies of patients with psoriasis before and during rhIL-11 treatment demonstrates a decrease in mRNA levels of TNF alpha, IFN gamma and iNOS. These activities suggest that in addition to its thrombopoietic clinical use, rhIL-11 may also be valuable in the treatment of inflammatory diseases. The clinical utility of the anti-inflammatory properties of rhIL-11 is being investigated in patients with Crohn's disease, psoriasis and rheumatoid arthritis. These diseases are believed to be initiated and maintained by activated CD4+ Th1 cells in conjunction with activated macrophages.
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PMID:Hematopoietic, immunomodulatory and epithelial effects of interleukin-11. 1048 79

Both anaemia of iron deficiency and anaemia of chronic disease are frequently encountered in inflammatory bowel disease. Anaemia of iron deficiency is mostly due to inadequate intake or loss of iron. Anaemia of chronic disease probably results from decreased erythropoiesis, secondary to increased levels of proinflammatory cytokines, reactive oxygen metabolites and nitric oxide. Assessment of the iron status in a condition associated with inflammation, such as inflammatory bowel disease, is difficult. The combination of serum transferrin receptor with ferritin concentrations, however, allows a reliable assessment of the iron deficit. The best treatment for anaemia of chronic disease is the cure of the underlying disease. Erythropoietin reportedly may increase haemoglobin levels in some of these patients. The anaemia of iron deficiency is usually treated with oral iron supplements. Iron supplementation may lead to an increased inflammatory activity through the generation of reactive oxygen species. To date, data from studies in animal models of inflammatory bowel disease support the theoretical disadvantage of iron supplementation in this respect. The results, however, cannot easily be extrapolated to the human situation, because the amount of supplemented iron in these experiments was much higher than the dose used in patients with iron deficiency.
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PMID:Iron and inflammatory bowel disease. 1128 71

Anemia is frequently observed in patients suffering from chronic inflammatory disorders. Recent in vitro data suggest that Th2 cytokines, such as IL-10, could be involved in its pathogenesis. We analyzed 1) changes in hemoglobin values in 329 patients with chronic active Crohn's disease receiving the anti-inflammatory cytokine IL-10 as part of a randomized, double-blind, placebo-controlled study, 2) serum iron parameters in a subgroup of these patients (n = 54), and 3) the in vitro effects of IL-10 on ferritin transcription and translation in human monocytic cells (THP-1) by means of Northern blot and immunoprecipitation after metabolic labeling. Patients receiving higher doses of IL-10 developed anemia and presented with a dose-dependent increase of ferritin and soluble transferrin receptor levels, an indicator of iron restriction to erythroid progenitor cells. According to our in vitro data, hyperferritinemia may result from direct stimulation of ferritin translation by IL-10 in activated monocytic cells, most likely by cytokine-mediated reduction of the binding affinity of translational repressors, iron-regulatory proteins, to the 5'-untranslated region of ferritin mRNA. In patients, all observed changes were most pronounced at the end of therapy (day +29), and thereafter hemoglobin levels and serum iron parameters returned to baseline levels within 4 wk of follow-up. Our data demonstrate that IL-10 causes anemia in patients with inflammatory bowel disease which may be referred to the induction of imbalances in iron homeostasis by the cytokine, leading to hyperferritinemia and limited iron availability to erythroid progenitor cells, a condition typically seen in the anemia of chronic inflammation.
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PMID:Role of IL-10 for induction of anemia during inflammation. 1216 51

The assessment of disease activity in inflammatory bowel disease is done using clinical parameters and various biological disease markers. Classical disease markers including erythrocyte sedimentation rate, acute phase proteins, such as orosomucoid and CRP, leukocyte and platelet counts, play an important role in the monitoring of disease activity. Furthermore, the determination of zinc, iron, ferritin, vitamin B12, and folic acid is important to avoid deficiencies in patients with severe disease or after surgeries. Stool cultures are helpful to detect bacterial or parasitic infections mimicking inflammatory bowel disease. The detection of specific antibodies such as pANCA, PAB and ASCA is helpful for the differential diagnosis Crohn's disease--ulcerative colitis.
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PMID:[Laboratory diagnosis in inflammatory bowel disease]. 1269 15

Anemia is the most common systemic complication of inflammatory bowel disease (IBD); so common that it is almost invariably not investigated and rarely treated. Several misconceptions are the reason for these clinical errors, and our goal will be to review them. The most common misconceptions are: anemia is uncommon in IBD; iron deficiency is also uncommon; just by treating the intestinal disease, anemia will be corrected; iron deficiency is the only cause for anemia in IBD; ferritin is an accurate parameter for the diagnosis of iron deficiency in IBD; the impact of anemia on the quality of life of IBD patients is limited; iron supplementation is rarely needed in IBD; high-dose oral iron solves the problem of iron malabsorption in IBD; intravenous (IV) iron is dangerous and of no proven benefit in IBD; IV iron is useful only for severe anemia; and erythropoietin has no role in the treatment of IBD anemia. These misconceptions are not evidence-based. On the contrary, there is enough evidence to support the following statements: (a) anemia is very common in IBD, (b) anemia should be investigated with care because many factors can be responsible, (c) treatment of anemia results in clear improvement in the objective parameters of well-being, especially in the quality of life, (d) IV iron is safe and effective in the treatment of iron deficiency anemia in IBD patients, and (e) erythropoietin is useful in a subset of patients with refractory anemia. Anemia diagnosis and treatment must not be neglected in IBD patients, and several misconceptions should be promptly abandoned.
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PMID:Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. 1847 54

Anaemia is the most frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A disabling complication of IBD, anaemia worsens the patient's general condition and quality of life, and increases hospitalization rates. The main types of anemia in IBD are iron deficiency anemia and anemia of chronic disease. The combination of the serum transferrin receptor with ferritin concentrations and inflammatory markers allows a reliable assessment of the iron status. Iron deficiency is usually treated with oral iron supplements. However, it is less effective in IBD and may lead to an increased inflammatory activity through the generation of reactive oxygen species. A systematic review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on the evidence from recent studies will be the focus of this article.
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PMID:[Pathophysiological-based diagnosis and therapy of iron-deficient anaemia in inflammatory bowel disease]. 1919 27

Ferric carboxymaltose (Ferinject(R)), a novel iron complex that consists of a ferric hydroxide core stabilized by a carbohydrate shell, allows for controlled delivery of iron to target tissues. Administered intravenously, it is effective in the treatment of iron-deficiency anaemia, delivering a replenishment dose of up to 1000 mg of iron during a minimum administration time of </=15 minutes. Results of several randomized trials have shown that intravenously administered ferric carboxymaltose rapidly improves haemoglobin levels and replenishes depleted iron stores in various populations of patients with iron-deficiency anaemia, including those with inflammatory bowel disease, heavy uterine bleeding, postpartum iron-deficiency anaemia or chronic kidney disease. It was well tolerated in clinical trials. Ferric carboxymaltose is, therefore, an effective option in the treatment of iron-deficiency anaemia in patients for whom oral iron preparations are ineffective or cannot be administered. Ferric carboxymaltose is a macromolecular ferric hydroxide carbohydrate complex, which allows for controlled delivery of iron within the cells of the reticuloendothelial system and subsequent delivery to the iron-binding proteins ferritin and transferrin, with minimal risk of release of large amounts of ionic iron in the serum. Intravenous administration of ferric carboxymaltose results in transient elevations in serum iron, serum ferritin and transferrin saturation, and, ultimately, in the correction of haemoglobin levels and replenishment of depleted iron stores. The total iron concentration in the serum increased rapidly in a dose-dependent manner after intravenous administration of ferric carboxymaltose. Ferric carboxymaltose is rapidly cleared from the circulation and is distributed primarily to the bone marrow ( approximately 80%) and also to the liver and spleen. Repeated weekly administration of ferric carboxymaltose does not result in accumulation of transferrin iron in patients with iron-deficiency anaemia. Intravenously administered ferric carboxymaltose was effective in the treatment of iron-deficiency anaemia in several 6- to 12-week, randomized, open-label, controlled, multicentre trials in various patient populations, including those with inflammatory bowel disease, heavy uterine bleeding or postpartum iron-deficiency anaemia, and those with chronic kidney disease not undergoing or undergoing haemodialysis. In most trials, patients received either ferric carboxymaltose equivalent to an iron dose of </=1000 mg (or 15 mg/kg in those weighing <66 kg) administered over </=15 minutes (subsequent doses administered at 1-week intervals) or oral ferrous sulfate at a dose equivalent to 65 mg iron three times daily or 100 mg iron twice daily. In one trial, patients with chronic kidney disease undergoing haemodialysis received 200 mg of iron intravenously either as ferric carboxymaltose or iron sucrose administered into the haemodialysis line two to three times weekly. In all trials, ferric carboxymaltose was administered until each patient had received his or her calculated total iron replacement dose. Haemoglobin-related outcomes improved in patients with iron-deficiency anaemia receiving ferric carboxymaltose. Treatment with ferric carboxymaltose was associated with rapid and sustained increases from baseline in haemoglobin levels. Ferric carboxymaltose was considered to be as least as effective as ferrous sulfate with regard to changes from baseline in haemoglobin levels or the proportion of patients achieving a haematopoietic response at various timepoints. In general, improvements in haemoglobin levels were more rapid with ferric carboxymaltose than with ferrous sulfate. In patients with chronic kidney disease undergoing haemodialysis, ferric carboxymaltose was at least as effective as iron sucrose. Ferric carboxymaltose also replenished depleted iron stores and improved health-related quality-of-life (HR-QOL) in patients with iron-deficiency anaemia. Recipients of ferric carboxymaltose demonstrated improvements from baseline in serum ferritin levels and transferrin saturation, as well as improvements from baseline in HR-QOL assessment scores. Ferric carboxymaltose was at least as effective as ferrous sulfate with regard to endpoints related to serum ferritin levels, transferrin saturation and HR-QOL. Ferric carboxymaltose was well tolerated in clinical trials in patients with iron-deficiency anaemia, with most drug-related adverse events considered to be mild to moderate in severity. Commonly reported drug-related adverse events include headache, dizziness, nausea, abdominal pain, constipation, diarrhoea, rash and injection-site reactions. The incidence of drug-related adverse events in patients receiving intravenous ferric carboxymaltose was generally similar to that in patients receiving oral ferrous sulfate. In general, rash and local injection-site reactions were more common with ferric carboxymaltose, whereas gastrointestinal adverse events were more frequent with ferrous sulfate. In patients with chronic kidney disease undergoing haemodialysis, a lower proportion of ferric carboxymaltose than iron sucrose recipients experienced at least one drug-related adverse event.
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PMID:Ferric carboxymaltose: a review of its use in iron-deficiency anaemia. 1940 53

Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD). In most trials, patients received either FCM doses of < or = 1000 mg, administered intravenously (i.v.) over < or = 15 min. or oral ferrous sulfate (FeSulf) 325 mg (65 mg iron), three times daily (t.i.d.), or 304 mg (100 mg iron), twice daily (b.i.d.). In one trial, patients on HD received 200 mg i.v. of either FCM or iron sucrose (ISC), two-to-three times weekly. In a pilot study in patients with CHF and CKD, patients received 200 mg of FCM by push injection compared with 200 mg of ISC slow injection. FCM was usually administered until the patient's calculated total iron replacement dose was achieved. Treatment with FCM improved indices of anemia (hemoglobin [Hb], ferritin and transferrin saturation [TSAT] values). In patients on HD with IDA secondary to CKD, FCM demonstrated comparable efficacy to ISC in achieving an increase in Hb. In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. Patients with PPA receiving FCM compared with those receiving oral iron achieved an Hb rise > or = 2.0 g/dl earlier (7 days compared with 14 days; p < 0.001), were more likely to achieve an Hb rise > or = 3.0 g/dl at any time beginning at day 14 (86.3% compared with 60.4%; p < 0.001), and achieve an Hb > 12.0 g/dl at the end of the study (Day 42; 90.5% compared with 68.6%, p < 0.01). Serum ferritin increased in the i.v. FCM treatment group, but not in the oral iron group. Differences between groups were significant at each study interval. TSAT increased significantly at every interval in both groups; however, FCM-treated patients showed higher TSAT at each interval after the first week. FCM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB. FCM also improved quality of life as well as functional symptoms and exercise capacity in patients with CHF. Safety data from more than 3000 patients showed that FCM was well tolerated. No safety concerns have been identified in breastfed infants of mothers receiving FCM. FCM is, therefore, an effective and well-tolerated option in the treatment of IDA.
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PMID:Efficacy and safety of ferric carboxymaltose in correcting iron-deficiency anemia: a review of randomized controlled trials across different indications. 2064 30

Anemia is the most prevalent extraintestinal complication of IBD. It can affect quality of life and ability to work, and can also increase the hospitalization rate in patients with IBD. Although the causes of anemia in IBD are multifactorial, iron deficiency anemia (IDA) is the most common. Assessment of the iron status of patients who have a condition associated with inflammation, such as IBD, by using common biochemical values is insufficient. However, new indices of iron metabolism (for instance ferritin:transferrin receptor ratio, reticulocyte hemoglobin content or percentage of hypochromic red blood cells) may help to improve the assessment of iron status in patients with IBD. The treatment of IDA traditionally involves oral iron supplementation. However, because of extensive gastrointestinal adverse effects, and data showing that the use of oral iron in IBD may be associated with disease exacerbation, current guidelines suggest that iron supplementation in IBD should be administered intravenously. This Review provides an overview of iron homeostasis in health before discussing diagnostic and therapeutic strategies for IDA in patients with IBD.
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PMID:Diagnosis and management of iron deficiency anemia in patients with IBD. 2092 67


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