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Eliezer Rachmilewitz

Publications and source records attributed to Eliezer Rachmilewitz.

7 recordsLinked to original sources
PubMed2006

Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera.

Beta-thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of beta-thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in beta-thalassaemia might suppress liver hepcidin expression. Sera from beta-thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from beta-thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by beta-thalassaemia major sera (r = 0.852, P < 0.0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from beta-thalassaemia intermedia patients. In contrast, the majority of sera from hereditary haemochromatosis patients induced an increase in HAMP expression, which correlated with transferrin (Tf) saturation (r = 0.765, P < 0.0099). Our results suggest that, in beta-thalassaemia, serum factors might override the potential effect of iron overload on HAMP expression, thereby providing an explanation for the failure to arrest excessive intestinal iron absorption in these patients.

Acute-Phase Proteins↗
PubMed2006

mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models.

beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of beta-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.

Acute-Phase Proteins↗
PubMed2006

Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants.

Sickle cell disease (SCD) is basically a red blood cell (RBC) disorder characterised by sickling and haemolysis, but platelets and polymorphonuclear neutrophils (PMN) are also involved. Oxidative damage may play a role in the pathogenesis of SCD. Using flow cytometry, we measured oxidative-state markers simultaneously in RBC, platelets and PMN obtained from 25 normal donors, nine homozygous (SS) patients and six SS/beta-thalassaemia patients. Reactive oxygen species (ROS) and reduced glutathione (GSH) were measured following staining of blood samples with fluorescence probes and gating on specific subpopulations based on size and granularity. Ten- to 30-fold higher ROS production and 20-50% lower GSH content were found in RBC, platelets and PMN from SCD patients versus those of their normal counterparts. This could in part account for the clinical manifestations, such as haemolysis, a hypercoagulable state, recurrent bacterial infections and vaso-occlusive incidences, in SCD. We further showed that exposure of SCD samples to antioxidants, such as N-acetyl-cysteine, vitamin C and vitamin E, decreased their oxidative stress. These results suggest that antioxidant treatment of patients with SCD could reduce oxidative damage to RBC, PMN and platelets, thereby alleviating symptoms associated with their pathology. The flow cytometry techniques presented herein could assist in monitoring the efficacy of such treatment.

Adolescent↗
PubMed2005

Beta-thalassemia.

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Antioxidants↗
PubMed2005

Prevalence of iron deficiency and anemia among strenuously trained adolescents.

PURPOSE: There is a lack of awareness among physicians, dieticians, and public health planners as to the prevalence of iron deficiency and anemia among adolescents undergoing strenuous physical training. The aim of this study was to estimate the prevalence of iron deficiency and anemia among male adolescents undergoing such activity. METHODS: We studied 292 male adolescents on the day of entry into a volunteer military unit. Hemoglobin (Hb), mean corpuscular volume, ferritin, iron, iron-transferrin saturation, and soluble transferrin receptor (TfR) were measured, and TfR-F index was calculated. RESULTS: The mean Hb level (+/-SD) in the study population was 14.7 +/- .9 g/dL (range, 10.8-16.8 g/dL), mean ferritin level was 50.6 +/- 32.6 ng/mL (range, 5.4-162.5 ng/mL), and mean iron level was 97.1 +/- 39.9 microg/dL (range, 24-267 microg/dL). The prevalence of anemia (Hb <14 g/dL) was 18.5%, and 3.4% had Hb concentrations less than 13 g/dL. Iron deficiency (ferritin <22 ng/mL) was present in 18% of the subjects, and 11.3% had ferritin levels less than 17 ng/mL. The mean soluble transferrin receptor concentration was 1.9 +/- .8 mg/L, and the mean TfR-F index was 1.21 +/- .57. CONCLUSIONS: Nearly 19% of the study subjects had mild anemia at recruitment, and depletion of iron stores was observed among 18%. Overall, these changes were not accompanied by a significant increase in soluble TfR. This high prevalence is most likely the result of "sports anemia" due to the intense physical training regimen adopted prior to their recruitment.

Adolescent↗