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Iron is an essential element to the well functionning of the organism and requires careful maintenance of its homeostasis. This is mainly due to hepcidin, a hormone secreted by the liver that controls the flow of iron within the body. It has a hyposideremic action by reducing the expression of ferroportin, the only protein known to this day, which can export iron into the extracellular environment. This has the effect of decreasing intestinal absorption and increasing intracellular retention, especially in macrophages. Hepcidin is stimulated by elevation of iron and inflammation while activation of erythropoiesis inhibits it. Understanding its regulation allows a better understanding of the pathophysiological mechanisms of overload diseases and iron deficiency. Therefore, hepcidin analysis is interesting for the exploration of iron homeostasis. In combination with other biological parameters of iron status, it is possible to find better instructions for therapeutic managements of iron metabolism diseases. Thus, an assaying method by coupling liquid chromatography and tandem mass spectrometry has been implemented at Grenoble University Hospital and the analytical performances of this assay met the laboratory requirements in terms of reliability of the analysis. [ABSTRACT FROM AUTHOR]

Les hémochromatoses bénéficient d'une grande clarification de leur nosologie grâce à la prise en compte des mécanismes qui sous-tendent le développement de la surcharge en fer. Ainsi, le dénominateur commun mécanistique est la déficience en hepcidine, hormone du métabolisme du fer, qui, en favorisant l'activité d'export cellulaire du fer par la ferroportine au niveau du duodénum et de la rate, entraîne une cascade : hyper-sidérémie, apparition de fer non lié à la transferrine, ciblage en premier lieu du foie par ce fer non lié, effet toxique cellulaire conduisant à l'endommagement d'organes clés et développement de la maladie hémochromatosique, source de morbidité et de mortalité. Chez le sujet caucasien, c'est l'hémochromatose liée au gène HFE qui est de loin la plus fréquente. Les hémochromatoses non liées à HFE sont rares, multi-ethniques et souvent sévères. L'apport de la biologie est majeur tant pour la compréhension de la physiopathologie (rôle de l'hypo-hepcidinémie) que pour l'évocation du diagnostic (coefficient de saturation de la transferrine, ferritinémie), pour l'identification étiologique (tests génétiques), et pour le suivi thérapeutique (importance de la ferritinémie et possiblement dans l'avenir de l'hepcidinémie). Le diagnostic des hémochromatoses est devenu totalement non invasif (basé sur la clinique, la biologie et l'imagerie) et sa thérapeutique, qui demeure basée sur les saignées, devrait faire appel dans l'avenir à des approches innovantes visant à restaurer un métabolisme du fer normal. Hemochromatoses benefit from a great clarification of their nosology thanks to the consideration of the mechanism underlying the development of iron overload. Thus, the mechanistic common denominator is hepcidin deficiency which, by stimulating the cellular iron export activity of ferroportin in the duodenum and the spleen, leads to a cascade: hyper-sideremia, appearance of non-transferrin bound iron that first targets the liver, and exerts cellular toxicity damaging key organs and corresponding to the development of hemochromatosis, that is source of morbidity and mortality. In the Caucasian subject, hemochromatosis linked to the HFE gene is by far the most frequent. Non HFE -related hemochromatoses are rare but multi-ethnic and often severe. The contribution of biology is major for the understanding of the pathophysiology (role of hypo-hepcidinemia), for the diagnosis (coefficient of transferrin saturation, ferritinemia) including the etiological identification (genetic tests), and for the therapeutic follow-up (importance of ferritinemia and possibly in the future of hepcidinemia). The diagnosis of hemochromatosis has become totally non-invasive (based on clinical, biological and imaging techniques) and its therapy, which remains based on phlebotomies, should in the future call for innovative approaches aimed at restoring normal iron metabolism. [ABSTRACT FROM AUTHOR]

Aksaray Malakli Shepherd Dog is a native Anatolian race which is raised in Aksaray and it is marked recently. This study is prepared to reveal significative biochemical properties of Aksaray Malakli Dog. Blood samples were collected from 20 Malakli dogs which are raised in various animal shelters in Aksaray region. Biochemical parameters; serum total protein, albumin, globulin, blood urea nitrogen, creatinine, glucose, total cholesterol, triglyceride, calcium, phosphor, iron, ferritin, and ALP, AST, ALT, creatine enzyme activities were measured calorimetrically. Obtained results were 6.25 g/dL, 3.62 g/dL, 2.63 g/dL, 16.53 mg/dL, 0.88 mg/dL, 91.10 g/dL, 186.85 mg/dL, 47.65 mg/dL, 9.53 mg/dL, 4.36 mg/dL, 112.45 µg/dL, 0.51 ng/dL respectively. and enzyme levels were 42.50 IU/L, 31.90 IU/L, 43.30 IU/L, 166.4 IU/L, respectively. Serum Paraoxonase 1 and hepcidine levels were measured with ELISA kits manually. Obtained results were 33.0 ng/ml and 23.55 ng/ml respectively. With this study, we determined some serum biochemical parameters of Malakli dog and we tried to find out the differences between the other Anadolu Çoban dogs. Obtained results may be useful for the next studies about morbidity-health status of these dogs.

Abstract Iron overload pathophysiology has benefited from significant advances in the knowledge of iron metabolism and in molecular genetics. As a consequence, iron overload nosology has been revisited. The hematologist may be confronted to a number of iron overload syndromes, from genetic or acquired origin. Hemochromatoses, mostly but not exclusively related to the HFE gene, correspond to systemic iron overload of genetic origin in which iron excess is the consequence of hepcidin deficiency, hepcidin being the hormone regulating negatively plasma iron. Iron excess develops following hypersideremia and the formation of non-transferrin-bound iron, which targets preferentially parenchymal cells (hepatocytes). The ferroportin disease has a totally different iron overload mechanism consisting of defective egress of cellular iron into the plasma, iron deposition taking place mostly within the macrophages (spleen). Hereditary aceruloplasminemia is peculiar since systemic iron overload involves the brain. Two main types of acquired iron overload can be seen by the hematologist, one related to dyserythropoiesis (involving hypohepcidinemia), the other related to multiple transfusions (thalassemias, myelodysplasia, hematopoietic stem cell transplantation). Congenital sideroblastic anemias, either monosyndromic (anemia) or polysyndromic (anemia plus extra-hematological syndromes), develop both compartimental iron excess within the erythroblast mitochondria, and systemic iron overload (through dyserythropoiesis and/or transfusions). [ABSTRACT FROM AUTHOR]

Numerous tests have been proposed as a diagnostic method for iron deficiency, with sometimes variable thresholds depending on the populations. Biomarkers are used to analyze the state of iron stocks according to the compartments where it is present. The state of intracellular iron stores is analyzed by hemoglobin levels, microcytosis, reticulocyte levels, hypochromic erythrocyte levels, and reticulocyte hemoglobin content. The iron storage compartments are analyzed via ferritin levels and myelogram data. The transport iron can be analyzed by the transferrin saturation, the soluble transferrin receptor level, and the transferrin/ferritin soluble receptor ratio. The biological formula will be different depending on the type of deficiency: absolute iron deficiency (low ferritin, low transferrin saturation factor), functional iron deficiency (normal or high ferritin, but low transferrin saturation), or even mixed deficiency (for example, absolute deficiency due to blood loss and functional deficiency due to inflammation). After martial supplementation (oral or parenteral), the markers described above will also be useful to confirm (or deny) the effectiveness of treatments. The kinetics of correction of abnormalities is as follows: transferrin saturation factor, hemoglobin level, ferritin level, and finally microcytosis. [ABSTRACT FROM AUTHOR]

Alcohol consumption during pregnancy places the fetus at risk for permanent physical, cognitive, and behavioral impairments, collectively termed fetal alcohol spectrum disorder (FASD). However, prenatal alcohol exposure (PAE) outcomes vary widely, and growing evidence suggests that maternal nutrition is a modifying factor. Certain nutrients, such as iron, may modulate FASD outcomes. Untreated gestational iron deficiency (ID) causes persistent neurodevelopmental deficits in the offspring that affect many of the same domains damaged by PAE. Although chronic alcohol consumption enhances iron uptake and elevates liver iron stores in adult alcoholics, alcohol-abusing premenopausal women often have low iron reserves due to menstruation, childbirth, and poor diet. Recent investigations show that low iron reserves during pregnancy are strongly associated with a worsening of several hallmark features in FASD including reduced growth and impaired associative learning. This review discusses recent clinical and animal model findings that maternal ID worsens fetal outcomes in response to PAE. It also discusses underlying mechanisms by which PAE disrupts maternal and fetal iron homeostasis. We suggest that alcohol-exposed ID pregnancies contribute to the severe end of the FASD spectrum. [ABSTRACT FROM AUTHOR]

Résumé En cas de stimulation de l’érythropoïèse, les besoins en fer de l’organisme augmentent afin de permettre la production de nouveaux érythrocytes. Dans les années 1950, l’observation d’une augmentation de l’absorption digestive du fer en cas de phlébotomie avait conduit à proposer l’existence d’un facteur érythroïde régulant la mise à disposition du fer pour l’érythropoïèse dans cette situation. L’hormone régulant l’homéostasie du fer a été identifiée en 2000, comme étant l’hepcidine. Tout récemment, en 2014, a été découvert un facteur de régulation du métabolisme du fer, indépendant de celui des stocks martiaux et répondant à l’augmentation des besoins en fer après stimulation de l’érythropoïèse par l’érythropoïétine. Ce facteur a été dénommé érythroferrone. Ainsi, la régulation des stocks de fer dépend de l’hepcidine, tandis que les phénomènes d’adaptation de la disponibilité du fer en cas d’érythropoïèse sont favorisés par un facteur érythroïde qui pourrait être l’érythroferrone. Cette revue synthétise l’état des connaissances sur le rôle supposé de l’érythroferrone dans le métabolisme du fer en s’appuyant sur les résultats expérimentaux, obtenus principalement sur des modèles murins, dans les surcharges martiales liées aux β-thalassémies, les perturbations martiales lors des anémies inflammatoires et l’insuffisance rénale chronique. Ces résultats devront être confrontés à ceux obtenus chez l’homme, dès qu’une méthode de dosage fiable de l’érythroferrone humaine sera disponible. D’un point de vue clinique, l’érythroferrone pourrait devenir un marqueur biologique du métabolisme du fer et une cible thérapeutique. In case of erythropoiesis, body iron needs to increase to enable the production of new red blood cells. In the 1950s, the observation of an increased digestive iron absorption in the case of phlebotomies had led to propose the existence of an “erythroid factor”, which regulate the availability of iron for erythropoiesis in this situation. The factor regulating iron stores has been identified in 2000 to be hepcidin. Recently, in 2014, a new factor was discovered, which regulates iron metabolism, independently of iron stores and responds to the increased requirements for iron after stimulation of erythropoiesis by erythropoietin. This factor has been referred to as erythroferrone. Thus, the regulation of iron stores depends on hepcidin, while the adaptation mechanisms of iron availability in case of anemia, are mediated by an erythroid factor that could be erythroferrone. This review summarizes the current knowledge on the role of erythroferrone in iron metabolism, starting from experimental results, obtained mainly on mouse models, and related to iron overload in β-thalassemia, iron disturbances during anemia of chronic diseases and chronic renal failure. These results will have to be compared with those obtained in humans, as soon as a reliable assay for human erythroferrone is available. From a clinical point of view, erythroferrone could become a useful biological marker of iron metabolism and a therapeutic target. [ABSTRACT FROM AUTHOR]

We determined the effects of repeated sprint exercise under normoxic and hypoxic conditions on serum hepcidin levels. Ten male athletes (age: 20.9 ± 0.3 years; height: 175.7 ± 6.0 cm; weight: 67.3 ± 6.3 kg) performed 2 exercise trials under normoxic (NOR; fraction of inspiratory oxygen (FiO2): 20.9%) or hypoxic conditions (HYPO; FiO2: 14.5%). The exercise consisted of 3 sets of 5 × 6 s of maximal pedaling (30-s rest periods between sprints, 10-min rest periods between sets). Blood samples were collected before exercise, immediately after exercise, and 1 and 3 h after exercise. Serum hepcidin levels were significantly elevated after exercise in both trials (both P < 0.01), with no significant difference between the trials. The postexercise blood lactate levels were significantly higher in the HYPO than the NOR ( P < 0.05). Both trials caused similar increases in plasma interleukin-6 and serum iron levels ( P < 0.001), with no significant difference between the trials. A significant interaction (trial × time) was apparent in terms of serum erythropoietin (EPO) levels ( P = 0.003). The EPO level was significantly higher in the HYPO than the NOR at 3 h after exercise ( P < 0.05). In conclusion, repeated sprint exercise significantly increased serum hepcidin levels to similar extent in 2 trials, despite differences in the inspired oxygen concentrations during both the exercise and the 3-h postexercise period. [ABSTRACT FROM AUTHOR]

Genetic medicine applied to the study of hemochromatosis has identified the systemic loop controlling iron homeostasis, centered on hepcidin-ferroportin interaction. Current challenges are to dissect the molecular pathways underlying liver hepcidin synthesis in response to circulatory iron, HFE, TFR2, HJV, TMPRSS6 and BMP6 functions, and to define the major structural elements of hepcidin-ferroportin interaction. We built a first 3D model of human ferroportin structure, using the crystal structure of EmrD, a bacterial drug efflux transporter of the Major Facilitator Superfamily, as template. The model enabled study of disease-associated mutations, and guided mutagenesis experiments to determine the role of conserved residues in protein stability and iron transport. Results revealed novel amino acids that are critical for the iron export function and the hepcidin-mediated inhibition mechanism: for example, tryptophan 42, localized in the extracellular end of the ferroportin pore and involved in both biological functions. Here, we propose a strategy that is not limited to structure analysis, but integrates information from different sources, including human disease-associated mutations and functional in vitro assays. The first major hypothesis of this PhD thesis is that ferroportin resistance to hepcidin relies on different molecular mechanisms that are critical for ferroportin endocytosis, and include at least three fundamental steps: (i) hepcidin binding to ferroportin, (ii) structural reorganization of the N- and C-ter ferroportin lobes, and (iii) ferroportin ubiquitination. [ABSTRACT FROM AUTHOR]

Iron homeostasis relies on the amount of its absorption by the intestine and its release from storage sites, the macrophages. Iron homeostasis is also dependent on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized predominantly by the liver, is the main regulator of iron metabolism. Hepcidin reduces serum iron by inhibiting the iron exporter, ferroportin expressed both tissues, the intestine and the macrophages. In addition, in the enterocytes, hepcidin inhibits the iron influx by acting on the apical transporter, DMT1. A defect of hepcidin expression leading to the appearance of a parenchymal iron overload may be genetic or secondary to dyserythropoiesis. The exploration of genetic hemochromatosis has revealed the involvement of several genes, including the recently described BMP6 . Non-transfusional secondary hemochromatosis is due to hepcidin repression by cytokines, in particular the erythroferone factor that is produced directly by the erythroid precursors. Iron overload is correlated with the appearance of a free form of iron called NTBI. The influx of NTBI seems to be mediated by ZIP14 transporter in the liver and by calcium channels in the cardiomyocytes. Beside the liver, hepcidin is expressed at lesser extent in several extrahepatic tissues where it plays its ancestral role of antimicrobial peptide. In the kidney, hepcidin modulates defense barriers against urinary tract infections. In the heart, hepcidin maintains tissue iron homeostasis by an autocrine regulation of ferroprotine expression on the surface of cardiomyocytes. In conclusion, hepcidin remains a promising therapeutic tool in various iron pathologies. [ABSTRACT FROM AUTHOR]

This study was conducted in Samarra, city on patients with amoebic dysentery and diarrhea for the period (1/12/ 2017 – 30/8/2018). The study included the examination of (600) stool samples of patients with diarrhea who were coming to the general Samarra hospital and medical clinics and took 30 samples with amoebic dysentery and 30 samples with diarrhea and anather 30 healthy samples as control. The results showed that 205 of tested samples were infected with amoebic dysentery (34.16%). Also, we have been studying and examining some of biochemical parameters of blood in patients with amoebic dysentery and diarrhea and for control group, these parameters are percentage of Ferritin, Hepsidin and Iron in serum and total iron band capacity (TIBC) and the results showed significant decrease (P≤0.05) in percentage of Ferritin, Iron and TIBC in patients with amoebic dysentery in compared with control group, while itwas increased (P≤0.05) in Hepcidin percentage. [ABSTRACT FROM AUTHOR]

Anemie komt frequent voor in de geriatrische populatie, voornamelijk bij geïnstitutionaliseerde en gehospitaliseerde ouderen. Bij een gehospitaliseerde geriatrische populatie zijn ijzer deficiënte anemie en anemie door chronische ziekte de meest voorkomende oorzaken. Voor de differentieeldiagnose is serumferritine-bepaling de meest gebruikte test, ondanks de lage sensitiviteit en matige specificiteit. Een beter begrip van de ijzerhomeostase leidt tot nieuwe diagnostische testen als serumhepcidine, serumtransferrinereceptor en hemoglobinegehalte in reticulocyten. Het belang van een goede diagnostiek en behandeling is in deze populatie groot, gezien de correlatie van anemie met morbiditeit en mortaliteit. Anemie bij ouderen wordt meestal gedefinieerd als een hemoglobinewaarde (Hb) < 12 g/dl voor vrouwen en < 13 g/dl voor mannen, alhoewel er geen eensgezindheid bestaat over een standaard hemoglobinewaarde waaronder onderzoek naar onderliggende pathologie zeker moet gestart worden. Dit dient steeds in functie van de algemene toestand van de patiënt geëvalueerd te worden.

Iron deficiency anemia is prevalent in subgroups of the Canadian population. The objective of this study was to examine iron status and anemia in preschool-age children. Healthy children ( n = 430, 2-5 years old, Montreal, Quebec, Canada) were sampled from randomly selected daycares. Anthropometry, demographics, and diet were assessed. Biochemistry included hemoglobin, ferritin, soluble transferrin receptors (sTfR), ferritin index, markers of inflammation (C-reactive protein, interleukin 6 (IL-6), and tumour necrosis factor alpha (TNFα)), and hepcidin. Iron deficiency and anemia cutoffs conformed to the World Health Organization criteria. Differences among categories were tested using mixed-model ANOVA or χ2 tests. Children were 3.8 ± 1.0 years of age, with a body mass index z score of 0.48 ± 0.97, and 51% were white. Adjusted intakes of iron indicated <1% were at risk for deficiency. Hemoglobin was higher in white children, whereas ferritin was higher with greater age and female sex. Inflammatory markers and hepcidin did not vary with any demographic variable. The prevalence of iron deficiency was 16.5% (95% confidence interval (CI), 13.0-20.0). Three percent (95% CI, 1.4-4.6) of children had iron deficiency anemia and 12.8% (95% CI, 9.6-16.0) had unexplained anemia. Children with iron deficiency, with and without anemia, had lower plasma ferritin and hepcidin but higher sTfR, ferritin index, and IL-6, whereas those with unexplained anemia had elevated TNFα. We conclude that iron deficiency anemia is not very common in young children in Montreal. While iron deficiency without anemia is more common than iron deficiency with anemia, the correspondingly reduced circulating hepcidin would have enabled heightened absorption of dietary iron in support of erythropoiesis. [ABSTRACT FROM AUTHOR]

Gaucher disease induces some metabolic abnormalities so increased serum ferritin appears in more than 60% at diagnosis. The storage of glucosylceramide in macrophages produces an inflammatory response with iron recycling deregulation and release of cytokines. Iron homeostasis is controlled by the circulating peptide hepcidin and its production is influenced by inflammatory cytokines. Iron damages cells by excess of catalyzing reactive oxygen species, removal of the excess iron has a positive influence on the response to treatment and survival in patients with iron overload. We have analyzed some inflammatory biomarkers of macrophage activation and related to the iron profile, including hepcidin and liver iron deposits determined by MRI, in 8 type 1 GD patients with hyperferritinemia. We have explored the changes in this profile after 4 months under therapy with two different iron chelators, deferoxamine or deferasirox, by evaluating response, adverse events and quality of life. We observed a significant reduction in serum ferritin and hepcidin levels and in liver iron deposits. No differences were observed in chitotriosidase activity, CCL18/PARC concentration and IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1β,TNF-α cytokine levels. After two years on follow-up, clinical and analytical data were improved and stable ferritin levels maintained less than 700 ng/dL. [ABSTRACT FROM AUTHOR]

Iron is a trace mineral that is highly significant to endurance athletes. Iron is critical to optimal athletic performance because of its role in energy metabolism, oxygen transport, and acid-base balance. Endurance athletes are at increased risk for suboptimal iron status, with potential negative consequences on performance, because of the combination of increased iron needs and inadequate dietary intake. This review paper summarizes the role of iron in maximal and submaximal exercise and describes the effects of iron deficiency on exercise performance. Mechanisms that explain the increased risk of iron deficiency in endurance athletes, including exercise-associated inflammation and hepcidin release on iron sequestration, are described. Information on screening athletes for iron deficiency is presented, and suggestions to increase iron intake through diet modification or supplemental iron are provided. [ABSTRACT FROM AUTHOR]

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Abstract: During the past 10years, the knowledge of iron metabolism has been revolutionized by the discovery of the main regulatory hormone of body iron: hepcidin. Meanwhile, new formulations of intravenous iron have been developed and are already or readily available. In this article, we review the recent pathophysiological mechanisms underlying anemia of chronic disease or due to iron deficiency. We describe the various treatment modalities of iron deficiency anemia using oral or intravenous route and the emerging indications of treatment with iron. Finally, we discuss the situations in which iron supplementation may be harmful. [Copyright &y& Elsevier]

Abstract: About 60% of body iron is associated with hemoglobin in circulating red blood cells and daily erythropoiesis requires about 25 to 30mg iron per day. This iron is provided by macrophages through recycling of heme iron following phagocytosis of senescent red blood cells and heme catabolism. Intestinal iron absorption (1 to 2mg per day) only compensates for daily iron losses. Hepcidin, a 25 amino-acid peptide synthesized in hepatocytes, secreted in plasma and rapidly removed in urines, is a negative regulator of both intestinal iron absorption and heme iron recycling by macrophages. Hepcidin synthesis is stimulated by iron or by inflammation (mostly by IL-6) and is repressed by iron deficiency and by all conditions that stimulate bone marrow erythropoiesis such as anemia, bleeding, hemolysis, dyserythropoiesis or erythropoietin injections. A defect in the activation of hepcidin normally triggered by iron excess is the underlying mechanism for all juvenile or adult forms of hemochromatosis whereas a defect in hepcidin repression is responsible for an iron deficiency iron refractory anemia (IRIDA). Reduced hepcidin filtration in renal insufficiency contributes to the associated anemia and stimulation of hepcidin synthesis by inflammation is a major determinant of the anemia of chronic disorders. New therapeutic perspectives are currently underway such as the development of agonists or antagonists of hepcidin or siRNA approaches aiming at reducing hepcidin synthesis. The validation of hepcidin assays in a near future will allow identifying the patients most likely to benefit from intravenous iron therapy. [Copyright &y& Elsevier]

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Abstract: Hereditary hemochromatosis is mainly due to the mutation p.Cys282Tyr of the HFE gene, but other genes may be involved. Advances in the knowledge of iron metabolism have helped highlight the central role of hepcidin. Arthropathies and osteoporosis are at the forefront both at the time of diagnosis than to the phase state because of their impact on quality of life. Joint symptoms are one of the main complaints of patients; osteoporosis increases the risk of fracture. The life-threatening complications of the disease (liver, heart, diabetes) are preventable by the introduction of phlebotomies to obtain the desaturation. This treatment usually does not affect articular manifestations of hemochromatosis but these must be treated (symptomatic and local treatments). It is important to inform the patient about the disease and its repercussions for him and his relatives. Finally, any unexplained osteoarthropathy should lead to a determination of transferrin saturation and ferritin to diagnose iron overload. [Copyright &y& Elsevier]

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Copyright of Revue Francophone des Laboratoires is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: The field of hereditary iron overload has known, in the recent period, deep changes mainly related to major advances in molecular biology. It encompasses now a series of genetic entities. The mechanistic understanding of iron overload development and iron toxicity has greatly improved. The diagnostic approach has become essentially noninvasive with a major role for biological tests. From the therapeutic viewpoint, the phlebotomy treatment is now enriched by the possibility of resorting to oral chelation and by innovative perspectives directly linked to our improvement in the molecular understanding of these diseases. [ABSTRACT FROM AUTHOR]

Abstract: Genetic hemochromatosis (GH) encompass a heterogeneous group of disorders, which is related to hepcidin deficiency (except type 4A of the ferroportin disease), leading to iron overload and eventually organ failure due to inappropriately high intestinal iron absorption. The most frequent entity remains HFE-related hemochromatois associated with the homozygosity for the p.Cys282Tyr mutation in the HFE gene (C282Y mutation), first identified in 1996. Several other genetic causes have been identified since 2000, often referred to as non-HFE hemochromatosis, resulting from mutations in genes involved in the regulation of iron homeostasis, such as transferrin receptor 2 (TRF2, type 3 GH), hepcidin (HAMP, type 2 GH), hémojuvelin (HJV, type 2 GH), ferroportin (SLC40A1, type 4 GH). Iron excess is due to deficiencies in either hepcidin, regulated by BMP6, or ferroportin (type 4A GH). So, several genes underlie the various forms of the disease, which have similar pathophysiological profiles but distinct clinical presentations. Additional genetic and environmental factors can modify the severity of the disease. The introduction of molecular tests into clinical practice has provided a tool for early diagnosis of these genetic diseases. [Copyright &y& Elsevier]

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Abstract: Objective: To evaluate the practice concerning the iron prescription by French intensivists. Type of study: Survey during an intensive care-national congress. Methods: Interviewed practitioners were separated in two groups (prescribing [P] iron once time or more per week; or not [NP] less than one time per month). Iron-treatments (iv or oral) efficacy and tolerance were quoted from 1 to 10. Results: All the 128 interviewed intensivists (73% male; mean age 36±8 years) considered having anaemic patients and 94% considered having patients with iron deficiency. For 72% of them, the iron deficiency was judged frequent (concerning >10% of their patients) and 25% were P. Intravenous iron, oral iron or both were used by, respectively, 20, 35 and 44% of the interviewed intensivists. Intravenous iron was considered more efficient (7±2 versus 6±2; p <0.001) and better tolerated (7±2 versus 6±2; p <0.001) than oral iron. There was no demographic difference between P and NP. P answered more often having patients with iron deficiency (p =0.04), but they did not perform biological tests for diagnosis of iron deficiency more often and did not consider iron-treatment efficacy or tolerance higher than NP. Conclusion: Intensive-care anaemia and iron deficiency were considered to be frequent and iron treatments to be efficient and quite well tolerated. But only 25% of the interviewed intensivists were frequent-iron prescribers. This survey underscore that iron prescription in ICU seems to rely more on clinical feeling than on strong evidence: it’s time to investigate! [Copyright &y& Elsevier]

Abstract: Hepcidin, originally identified as a 25 amino acid antimicrobial peptide made in the liver, is a key regulator of iron balance and recycling in humans and mice. Closely related hepcidin genes and peptides have also been identified in a number of fish species and in teleosts are thought to function as endogenous antibiotics involved in host defense against infection. Here we report the transcriptional regulation of hepcidin expression by infection and anemia in the channel catfish. Changes in hepcidin expression in catfish challenged with Edwardsiella ictaluri and in fish affected by channel catfish anemia (CCA) were measured by real time quantitative PCR. Hepcidin transcript levels in the livers were increased 4, 19, and 22-fold at 4, 24, and 48h following bacterial challenge, respectively. However, augmented hepcidin expression in the intestine and olfactory sac was detected only at 48h post-infection. Hepcidin transcript levels in the livers of catfish affected by CCA were less than 14% of that present in healthy counterparts. Hepatic hepcidin transcript levels correlated significantly with serum iron concentrations (, ) and with the percent saturation of transferrin (, ). Similar to mammalian hepcidins, channel catfish hepcidin is an iron-responsive gene and may also play important roles in innate host defense to infection and in iron homeostasis. Mammalian hepcidins may have evolved from an antimicrobial peptide and its structure and transcriptional regulatory mechanisms have been conserved throughout vertebrate evolution. [Copyright &y& Elsevier]

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Abstract: Most of the iron required for erythropoiesis is provided by heme iron recycling following degradation of senescent erythrocytes by tissue macrophages. Accumulation of biochemical modifications at the red blood cell membrane during ageing (externalisation of phosphatidyl-serine, peroxydation of membrane-bound lipoproteins, loss of sialic acid residues and formation of senescence neoantigens) constitute a series of signals that will allow the macrophage to identify the red blood cells to be eliminated, through interaction with specific receptors. After this initial recognition step, the red blood cell is internalised by phagocytosis, and phagosome maturation, which can comprise recruitment of the endoplasmic reticulum, will favour degradation of red blood cell constituents. Heme is catabolised by heme oxygenase 1, anchored in the endoplasmic reticulum membrane. A fraction of the released iron will be recycled back to the plasma through ferroportin, a membrane-bound Fe (II) export molecule, and a fraction will retained within the ferritin molecules, to be released at later stages. Multiple evidence coming from human diseases (type 4 hemochromatosis) and animal models indicate that ferroportin is essential for heme iron recycling by macrophages. Furthermore, ferroportin seems to be the molecular target of hepcidin, this circulating peptide synthesized by the liver and acting as a negative regulator of intestinal iron absorption and iron recycling by macrophages. Perturbations in erythrophagocytosis play a physiopathological role in several diseases, including hemochromatosis, anemia of chronic disorders and thalassemia. [Copyright &y& Elsevier]

Abstract: HFE hemochromatosis is the most frequent genetic iron overload disease. It is linked to the C282Y mutation of the HFE protein, protein encoded by the HFE gene, which is located on chromosome 6. The mechanisms accounting for iron excess are not only digestive hyperabsorption of iron but also excessive recycling of macrophagic iron coming from erythrophagocytosis and secreted into the blood. Both mechanisms are linked to an HFE-related hepatic failure in producing hepcidin, a key hormone of body iron regulation. The marked phenotypic variability of C282Y homozygosity expression is likely related to both genetic and environmental factors. The HFE gene discovery has rendered non invasive the positive diagnostic of HFE hemochromatosis, which is now based first on an increased level of plasma transferrin saturation leading to the request of the HFE mutation. Then, hepatic MRI is a reliable method to quantify iron overload. The HFE gene discovery has also paved the road of an enlarged field of differential diagnoses corresponding to novel entities of non-HFE related genetic iron overload syndromes. [Copyright &y& Elsevier]

Abstract: Purpose. – Advances towards the understanding of gene regulation and protein function recently discovered through iron metabolism disorders are the subject of this review. Current knowledge and key points. – Within a few years the discovery of genes that determine heritable defects of cellular iron uptake or regulation in mice as in humans have provided new insights for investigation into iron metabolism pathways. Future prospects and projects. – It is still unclear how connections are made between new proteins in iron uptake, trafficking and regulation of iron homeostasis. Gene expression studies using microarrays technology in different iron conditions should help to explore iron homeostasis further. [Copyright &y& Elsevier]

Copyright of EMC-Hepatologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)