Regulating the master iron regulator hepcidin

The inflammatory cytokine IL-6 directly regulates hepcidin through induction and subsequent promoter binding of STAT3. Clarification of the mechanism regulating hepcidin may allow the development of innovative therapeutic interventions for clinical conditions of abnormal iron homeostasis. ..

Anemia of chronic disease

This book summarizes the most current research on the anemia of chronic disease and identifies effective diagnostic strategies for this common clinical condition-covering key topics related to the design and selection of therapeutic options including the treatment of the underlying disease, the biology of erythropoietin and the regulation of erythropoiesis, the disturbance of iron homeostasis, and the complex nature of the systemic inflammatory response

The clinical relevance of detectable plasma iron species in iron overload states and subsequent to intravenous iron-carbohydrate administration

Many disorders of iron homeostasis (e.g., iron overload) are associated with dynamic kinetic profiles of multiple non-transferrin bound iron (NTBI) species, chronic exposure to which is associated with deleterious end-organ effects. Here we discuss the chemical nature of NTBI species, challenges with measuring NTBI in plasma and the clinical relevance of NTBI exposure based on source (iron overload disorder vs. intravenous iron-carbohydrate complex administration). NTBI is not a single entity but consists of multiple, often poorly characterized species, some of which are kinetically non-exchangeable while others are relatively exchangeable. Prolonged presence of plasma NTBI is associated with excessive tissue iron accumulation in susceptible tissues with consequences such as endocrinopathy and heart failure. By contrast, intravenous iron-carbohydrate nanomedicines administration leads only to transient NTBI appearance and lacks evidence for association with adverse clinical outcomes. Assays to measure plasma NTBI are typically technically complex and remain chiefly a research tool. There have been two general approaches to estimating NTBI: capture assays and redox-activity assays. Early assays could not avoid capturing some iron from transferrin thus overestimating NTBI. By contrast some later assays may have promoted the donation of NTBI species to transferrin during the assay procedure, potentially underestimating NTBI levels. The levels of transferrin saturation at which NTBI species have been detectable have varied between different methodologies and between patient populations studied. This article is protected by copyright. All rights reserved

Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion.

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.Journal Articleinfo:eu-repo/semantics/publishe