The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Eliezer A Rachmilewitz - One of the best experts on this subject based on the ideXlab platform.
-
cerebrovascular accident in β thalassemia major β tm and β thalassemia intermedia β ti
American Journal of Hematology, 2008Co-Authors: Mehran Karimi, Maryam Khanlari, Eliezer A RachmilewitzAbstract:Chronic hypercoagulable state expressed clinically by thromboembolic events has been described in thalassemia. One of the affected organs is the brain where symptomatic and asymptomatic damage has been reported. The present report describes seven cases who presented with the signs of cerebrovascular accident (CVA), five ischemic and two with hemorrhage. Two of them died. All patients were splenectomized, five received regular blood transfusions, and their ferritin levels were between 1,200 and 3,000 mg %. In addition, four patients had congestive heart failure and atrial fibrillation, and three had "Bronze Diabetes," The recommendation on the basis of the results is that well-designed clinical trials are indicated to monitor asymptomatic brain damage by magnetic resonance imaging in splenectomized patients over the age of 20 years, who are not regularly transfused and have a high risk to develop thromboembolic events. In this subset of patients, anticoagulant and/or antiplatelet therapy should be considered. Moreover, treatment of additional complications resulting from iron overload, which may contribute to the etiology of CVA such as cardiac failure and arrhythmia with or without "Bronze Diabetes," is mandatory.
Mehran Karimi - One of the best experts on this subject based on the ideXlab platform.
-
cerebrovascular accident in β thalassemia major β tm and β thalassemia intermedia β ti
American Journal of Hematology, 2008Co-Authors: Mehran Karimi, Maryam Khanlari, Eliezer A RachmilewitzAbstract:Chronic hypercoagulable state expressed clinically by thromboembolic events has been described in thalassemia. One of the affected organs is the brain where symptomatic and asymptomatic damage has been reported. The present report describes seven cases who presented with the signs of cerebrovascular accident (CVA), five ischemic and two with hemorrhage. Two of them died. All patients were splenectomized, five received regular blood transfusions, and their ferritin levels were between 1,200 and 3,000 mg %. In addition, four patients had congestive heart failure and atrial fibrillation, and three had "Bronze Diabetes," The recommendation on the basis of the results is that well-designed clinical trials are indicated to monitor asymptomatic brain damage by magnetic resonance imaging in splenectomized patients over the age of 20 years, who are not regularly transfused and have a high risk to develop thromboembolic events. In this subset of patients, anticoagulant and/or antiplatelet therapy should be considered. Moreover, treatment of additional complications resulting from iron overload, which may contribute to the etiology of CVA such as cardiac failure and arrhythmia with or without "Bronze Diabetes," is mandatory.
Maryam Khanlari - One of the best experts on this subject based on the ideXlab platform.
-
cerebrovascular accident in β thalassemia major β tm and β thalassemia intermedia β ti
American Journal of Hematology, 2008Co-Authors: Mehran Karimi, Maryam Khanlari, Eliezer A RachmilewitzAbstract:Chronic hypercoagulable state expressed clinically by thromboembolic events has been described in thalassemia. One of the affected organs is the brain where symptomatic and asymptomatic damage has been reported. The present report describes seven cases who presented with the signs of cerebrovascular accident (CVA), five ischemic and two with hemorrhage. Two of them died. All patients were splenectomized, five received regular blood transfusions, and their ferritin levels were between 1,200 and 3,000 mg %. In addition, four patients had congestive heart failure and atrial fibrillation, and three had "Bronze Diabetes," The recommendation on the basis of the results is that well-designed clinical trials are indicated to monitor asymptomatic brain damage by magnetic resonance imaging in splenectomized patients over the age of 20 years, who are not regularly transfused and have a high risk to develop thromboembolic events. In this subset of patients, anticoagulant and/or antiplatelet therapy should be considered. Moreover, treatment of additional complications resulting from iron overload, which may contribute to the etiology of CVA such as cardiac failure and arrhythmia with or without "Bronze Diabetes," is mandatory.
Laura Silvestri - One of the best experts on this subject based on the ideXlab platform.
-
L (2011) Molecular mechanisms regulating hepcidin revealed by hepcidin disorders
2020Co-Authors: Clara Camaschella, Laura SilvestriAbstract:Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (ironrefractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders. KEYWORDS: iron, iron metabolism, hepcidin, erythropoiesis, anemia INTRODUCTION Iron is an essential element for life since it modulates fundamental processes, such as hemoglobin synthesis, oxygen transport, and cell respiration and proliferation. However, due to its propensity to release electrons and produce reactive oxygen species, excess iron is toxic. For this reason, several regulatory mechanisms have been developed in mammals to avoid iron overload and to regulate iron uptake, utilization, release, and storage, according to cell and organism needs 1358 The Iron Regulator Hepcidin Hepcidin, the central iron regulator, is a small peptide produced by the hepatocytes in response to increased body iron and inflammation. Hepcidin binds to the iron exporter ferroportin on duodenal enterocytes and macrophages, triggering its internalization and lysosomal degradation 1359 Hepcidin expression is enhanced by inflammatory cytokines, especially IL-6, which binds to its receptor, activating JAK2 signaling and STAT3 phosphorylation The BMP-SMAD pathway and hepcidin transcription are both down-regulated in hypoxia, iron deficiency, and erythropoietic expansion, but the molecular mechanisms of this down-regulation are unclear The hepcidin identification has dramatically changed our understanding of the systemic regulation of iron metabolism and the pathophysiology of inherited iron disorders, now explained based on hepcidin dysregulation. In addition, it has allowed the recognition of new disorders, such as iron-refractory irondeficiency anemia (IRIDA) GENETIC DISORDERS OF THE HEPCIDIN PATHWAY Disorders Caused by Hepcidin Deficiency Hepcidin deficiency leads to excessive ferroportin function and systemic iron overload, with iron accumulation and toxicity in parenchymal cells of the liver and other organs. Genetic iron overload (hereditary hemochromatosis) was first described in the 19 th century as "Bronze Diabetes" because of the recognizable clinical complications due to excess tissue iron deposition, i.e., Diabetes and dark skin. At present, using genetic tests, the hemochromatosis genotype may be diagnosed as early as at the stage of genetic susceptibility to develop iron overload, before the development of any clinical complications Juvenile hemochromatosis is a recessive hemochromatosis due to HJV mutations. HJV is a GPIlinked membrane protein, which is a BMP coreceptor essential for iron-mediated hepcidin activation 1360 Acquired hepcidin deficiency Iron-loading anemias Excessive hepcidin inhibition Anemia, iron overload Acquired hepcidin overexpression Hepcidin-producing adenoma Inappropriate hepcidin expression Microcytic anemia Inflammation (acute, chronic) IL-6-induced hepcidin expression Anemia of inflammation, ACD TfR2-hemochromatosis is a further type of recessive disease, whose expression (early onset, but moderate severity) differs from both HFE-related and juvenile hemochromatosis, suggesting that TfR2 exerts more complex functions than that of a simple HFE partner. In agreement, Hfe-/-mice have less severe iron overload than Tfr2-/-mice and the double knockout has the most severe phenotype Ferroportin is the functional receptor of hepcidin and is essential for life Animal models are available for all hemochromatosis types (for review, see Supplemental Some murine models of iron overload due to extremely low hepcidin levels have been described that do not have a human correspondent, such as beta2-microglobulin knockout Bmp6 is up-regulated in response to iron overload in Hfe-/-mice, but Smad signaling and hepcidin levels are down-regulated In conclusion, hemochromatosis results from the interruption of the regulatory axis that activates hepcidin in response to increased body iron. A unifying model relies on hepcidin dysregulation, either decreased hepcidin in recessive diseases due to mutations of HFE, TfR2, HJV, hepcidin, or due to hepcidin resistance in selected ferroportin mutations. Disorders Caused by Hepcidin Excess Hepcidin overexpression was first shown to cause iron deficiency anemia in hepcidin transgenic mice Molecular defects inactivating TMPRSS6 cause the inherited disorder called iron-refractory irondeficiency anemia (IRIDA) in humans 1362 HEPCIDIN IN ACQUIRED DISORDERS Hepcidin Deficiency in Acquired Disorders Hepcidin deficiency was first reported in beta-thalassemia patients and then shown to be a feature of the so-called "iron-loading anemias". These anemias are characterized by high degrees of ineffective erythropoiesis and high iron stores. However, despite iron overload, hepcidin is not increased. They are considered a model to study the "erythroid regulator". This concept was defined by Clement Finch more than 30 years ago to indicate the strong signal that leads to increased iron absorption according to the erythropoiesis needs, irrespective of the iron stores Other conditions in which hepcidin is reduced are severe liver disease and alcoholic liver disease, characterized by iron overload, due to insufficient hepcidin production. Moderate hepcidin decrease in chronic viral C hepatitis has been reported[61] due to viral-mediated suppression of hepcidin productio
Clara Camaschella - One of the best experts on this subject based on the ideXlab platform.
-
L (2011) Molecular mechanisms regulating hepcidin revealed by hepcidin disorders
2020Co-Authors: Clara Camaschella, Laura SilvestriAbstract:Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (ironrefractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders. KEYWORDS: iron, iron metabolism, hepcidin, erythropoiesis, anemia INTRODUCTION Iron is an essential element for life since it modulates fundamental processes, such as hemoglobin synthesis, oxygen transport, and cell respiration and proliferation. However, due to its propensity to release electrons and produce reactive oxygen species, excess iron is toxic. For this reason, several regulatory mechanisms have been developed in mammals to avoid iron overload and to regulate iron uptake, utilization, release, and storage, according to cell and organism needs 1358 The Iron Regulator Hepcidin Hepcidin, the central iron regulator, is a small peptide produced by the hepatocytes in response to increased body iron and inflammation. Hepcidin binds to the iron exporter ferroportin on duodenal enterocytes and macrophages, triggering its internalization and lysosomal degradation 1359 Hepcidin expression is enhanced by inflammatory cytokines, especially IL-6, which binds to its receptor, activating JAK2 signaling and STAT3 phosphorylation The BMP-SMAD pathway and hepcidin transcription are both down-regulated in hypoxia, iron deficiency, and erythropoietic expansion, but the molecular mechanisms of this down-regulation are unclear The hepcidin identification has dramatically changed our understanding of the systemic regulation of iron metabolism and the pathophysiology of inherited iron disorders, now explained based on hepcidin dysregulation. In addition, it has allowed the recognition of new disorders, such as iron-refractory irondeficiency anemia (IRIDA) GENETIC DISORDERS OF THE HEPCIDIN PATHWAY Disorders Caused by Hepcidin Deficiency Hepcidin deficiency leads to excessive ferroportin function and systemic iron overload, with iron accumulation and toxicity in parenchymal cells of the liver and other organs. Genetic iron overload (hereditary hemochromatosis) was first described in the 19 th century as "Bronze Diabetes" because of the recognizable clinical complications due to excess tissue iron deposition, i.e., Diabetes and dark skin. At present, using genetic tests, the hemochromatosis genotype may be diagnosed as early as at the stage of genetic susceptibility to develop iron overload, before the development of any clinical complications Juvenile hemochromatosis is a recessive hemochromatosis due to HJV mutations. HJV is a GPIlinked membrane protein, which is a BMP coreceptor essential for iron-mediated hepcidin activation 1360 Acquired hepcidin deficiency Iron-loading anemias Excessive hepcidin inhibition Anemia, iron overload Acquired hepcidin overexpression Hepcidin-producing adenoma Inappropriate hepcidin expression Microcytic anemia Inflammation (acute, chronic) IL-6-induced hepcidin expression Anemia of inflammation, ACD TfR2-hemochromatosis is a further type of recessive disease, whose expression (early onset, but moderate severity) differs from both HFE-related and juvenile hemochromatosis, suggesting that TfR2 exerts more complex functions than that of a simple HFE partner. In agreement, Hfe-/-mice have less severe iron overload than Tfr2-/-mice and the double knockout has the most severe phenotype Ferroportin is the functional receptor of hepcidin and is essential for life Animal models are available for all hemochromatosis types (for review, see Supplemental Some murine models of iron overload due to extremely low hepcidin levels have been described that do not have a human correspondent, such as beta2-microglobulin knockout Bmp6 is up-regulated in response to iron overload in Hfe-/-mice, but Smad signaling and hepcidin levels are down-regulated In conclusion, hemochromatosis results from the interruption of the regulatory axis that activates hepcidin in response to increased body iron. A unifying model relies on hepcidin dysregulation, either decreased hepcidin in recessive diseases due to mutations of HFE, TfR2, HJV, hepcidin, or due to hepcidin resistance in selected ferroportin mutations. Disorders Caused by Hepcidin Excess Hepcidin overexpression was first shown to cause iron deficiency anemia in hepcidin transgenic mice Molecular defects inactivating TMPRSS6 cause the inherited disorder called iron-refractory irondeficiency anemia (IRIDA) in humans 1362 HEPCIDIN IN ACQUIRED DISORDERS Hepcidin Deficiency in Acquired Disorders Hepcidin deficiency was first reported in beta-thalassemia patients and then shown to be a feature of the so-called "iron-loading anemias". These anemias are characterized by high degrees of ineffective erythropoiesis and high iron stores. However, despite iron overload, hepcidin is not increased. They are considered a model to study the "erythroid regulator". This concept was defined by Clement Finch more than 30 years ago to indicate the strong signal that leads to increased iron absorption according to the erythropoiesis needs, irrespective of the iron stores Other conditions in which hepcidin is reduced are severe liver disease and alcoholic liver disease, characterized by iron overload, due to insufficient hepcidin production. Moderate hepcidin decrease in chronic viral C hepatitis has been reported[61] due to viral-mediated suppression of hepcidin productio
