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Motoko Tanaka, Kazuki Yoshida, Shingo Fukuma, Kazuko Ito, Kazutaka Matsushita, Masafumi Fukagawa, Shunichi Fukuhara, Tadao Akizawa
OBJECTIVES: Anemia is an important prognostic factor in hemodialysis patients. It has been reported that parathyroidectomy ameliorates anemia and reduces the requirement of postoperative erythropoiesis-stimulating agents. The objective of this study was to assess the effect of cinacalcet, which is considered as a pharmacological parathyroidectomy, on anemia in hemodialysis patients. METHODS: We used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism; the criteria were: intact parathyroid hormone concentrations ≥ 180 pg/mL or use of an intravenous or oral vitamin D receptor activator...
2016: PloS One
Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Achiya Zvi Amir, Gadi Horev, Joanne Yacobovich, Michael Bennett, Hannah Tamary
The congenital dyserythropoietic anemias (CDAs) are a group of rare genetic disorders characterized by ineffective erythropoiesis and the development of secondary hemochromatosis. Distal limb anomalies are a well-documented though rare feature of congenital dyserythropoietic anemia type I, that have not been reported so far in other types. We describe a patient with congenital dyserythropoietic anemia type II and four members of a family with clinical features of congenital dyserythropoietic anemia type III with distal limb anomalies...
October 19, 2016: American Journal of Medical Genetics. Part A
Nicolas Leuenberger, Emanuele Bulla, Olivier Salamin, Raul Nicoli, Neil Robinson, Norbert Baume, Martial Saugy
The concentration of hepcidin, a key regulator of iron metabolism, is suppressed during periods of increased erythropoietic activity. The present study obtained blood samples from 109 elite athletes and examined the correlations between hepcidin and markers of erythropoiesis and iron metabolism (i.e., hemoglobin, erythropoietin (EPO), ferritin, erythroferrone (ERFE), and iron concentration). Furthermore, an administration study was undertaken to examine the effect of recombinant human EPO (rhEPO) delta (Dynepo™) on hepcidin concentrations in healthy male volunteers...
October 18, 2016: Drug Testing and Analysis
George Moschonis, Ellen G H M van den Heuvel, Christina Mavrogianni, Cécile M Singh-Povel, Michalis Leotsinidis, Yannis Manios
The benefits of dairy consumption seem to extend beyond its significant contribution to ensuring nutrient intake adequacy as indicated by the favourable associations with several health outcomes reported by different studies. The aims of the present study were to examine the associations of milk consumption with fitness, anthropometric and biochemical indices in children and further explore whether the observed associations are attributed to vitamins B₂ and B12 derived from milk. A representative subsample of 600 children aged 9-13 years participating in the Healthy Growth Study was examined...
October 13, 2016: Nutrients
Yu Seob Shin, Jae Hyung You, Jai Seong Cha, Jong Kwan Park
OBJECTIVE: To investigate the relationship between serum total testosterone (TT) and free testosterone (FT) levels in men with anemia. METHODS: We reviewed the records of 1221 subjects between March 2009 and December 2014. All the subjects' blood samples were drawn for TT and FT assays. Their serum hemoglobin (Hb) and serum hematocrit (Hct) levels were measured. The primary objective of our study was to investigate the association between TT and FT levels with Hb and Hct levels...
October 18, 2016: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
Francesca Lupo, Elena Tibaldi, Alessandro Matte, Alok K Sharma, Anna Maria Brunati, Seth L Alper, Carlo Zancanaro, Donatella Benati, Angela Siciliano, Mariarita Bertoldi, Francesca Zonti, Alexander Storch, Ruth H Walker, Adrian Danek, Benedikt Bader, Andreas Hermann, Lucia De Franceschi
Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red-cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1, Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation...
October 14, 2016: Blood
Christina M Wyatt, Tilman B Drüeke
The treatment of anemia with erythropoiesis-stimulating agents and iron supplementation has become the standard of care in patients with chronic kidney disease. Because of the risks associated with this approach, hypoxia inducible factor stabilizing prolyl hydroxylase inhibitors were developed as a potential treatment alternative. In recent phase 2 trials, these agents raised hemoglobin in a predictable and controlled manner and improved markers of iron metabolism. More experience is needed to establish long-term efficacy, tolerability, and safety, and to determine whether their use is associated with lower iron requirements...
November 2016: Kidney International
Rebecca Baum, Shruti Sharma, Jason M Organ, Christopher Jakobs, Veit Hornung, David B Burr, Ann Marshak-Rothstein, Katherine A Fitzgerald, Ellen M Gravallese
OBJECTIVE: Cytosolic DNA sensors detect microbial DNA and promote type I interferon and pro-inflammatory cytokine production through the adaptor stimulator of interferon genes (STING) to resolve infection. Endogenous DNA also engages the STING pathway, contributing to autoimmune disease. We identified a novel role for STING in bone in arthritic DNase II/IFNaR double deficient (DKO) mice, and sought to define the bone phenotype in these mice and to address mechanism. METHODS: Bone parameters were evaluated in DKO, STING/DNaseII/IFNaR triple deficient and control mice by microcomputed tomography and histomorphometry...
October 14, 2016: Arthritis & Rheumatology
Naoya Uchida, Juan J Haro-Mora, Atsushi Fujita, Duck-Yeon Lee, Thomas Winkler, Matthew M Hsieh, John F Tisdale
Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell-derived erythroid cells predominantly produce ε- and γ-globin without β-globin production. We recently demonstrated that ES cell-derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β-globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation...
October 14, 2016: Stem Cells
Umberto Gianelli, Daniele Cattaneo, Anna Bossi, Ivan Cortinovis, Leonardo Boiocchi, Yen-Chun Liu, Claudia Augello, Arturo Bonometti, Stefano Fiori, Nicola Orofino, Francesca Guidotti, Attilio Orazi, Alessandra Iurlo
In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Patrick Biggar, Frank Leistikow, Andreas Walper
AIMS: The aim of this study was to investigate the effectiveness, safety, and tolerability of iron isomaltoside in routine practical care of iron deficiency anemia (IDA) in patients with chronic renal failure. METHODS: The study included 698 patients with IDA on dialysis or with nondialysis chronic kidney disease (CKD) stages 3 - 5 designated by their physicians for treatment with iron isomaltoside. Data were recorded at baseline and after 3 and 9 months. Effectiveness data included measurement of hemoglobin (Hb), hematocrit, s-iron, transferrin saturation (TSAT), and s-ferritin...
October 14, 2016: Clinical Nephrology
Yanming Li, Qian Zhang, Zhenglin Du, ZhiChao Lu, Shuge Liu, Lu Zhang, Nan Ding, Binghao Bao, Yadong Yang, Qian Xiong, Hai Wang, Zhaojun Zhang, Hongzhu Qu, Haibo Jia, Xiangdong Fang
Previous studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid-inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF-1 cells confirmed its inhibitory role in erythroid differentiation...
October 13, 2016: British Journal of Haematology
Hannah L Bader, Tien Hsu
BACKGROUND: Mutations in the tumor suppressor gene von Hippel-Lindau (VHL) underlie a hereditary cancer syndrome-VHL disease-and are also frequently observed in sporadic renal cell carcinoma of the clear cell type (ccRCC). VHL disease is characterized by malignant and benign tumors in a few specific tissues, including ccRCC, hemangioblastoma and pheochromocytoma. The etiology of these tumors remains unresolved. METHODS: Conditional inactivation of the VHL gene in mouse (Vhlh) was generated to examine the pathophysiological role of the VHL gene function...
October 12, 2016: BMC Cancer
Tomas Ganz
Hepcidin is an iron-regulating peptide hormone made in the liver. It controls the delivery of iron to blood plasma from intestinal cells absorbing iron, from erythrocyte-recycling macrophages, and from iron-storing hepatocytes. Hepcidin acts by binding to and inactivating the sole cellular iron exporter, ferroportin, which delivers iron to plasma from all iron-transporting cells. In a classical endocrine feedback system, hepcidin production is stimulated by plasma iron and iron stores. Reflecting a likely role of hepcidin in innate immunity, hepcidin is also induced by inflammation...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Bin Mao, Shu Huang, Xulin Lu, Wencui Sun, Ya Zhou, Xu Pan, Jinfeng Yu, Mowen Lai, Bo Chen, Qiongxiu Zhou, Song Mao, Guohui Bian, Jiaxi Zhou, Tatsutoshi Nakahata, Feng Ma
The development of human erythroid cells has been mostly examined in models of adult hematopoiesis, while their early derivation during embryonic and fetal stages is largely unknown. We observed the development and maturation of erythroblasts derived from human pluripotent stem cells (hPSCs) by an efficient co-culture system. These hPSC-derived early erythroblasts initially showed definitive characteristics with a glycophorin A(+) (GPA(+)) CD34(low)CD36(-) phenotype and were distinct from adult CD34(+) cell-derived ones...
October 4, 2016: Stem Cell Reports
Leo Kager, Lesley J Bruce, Petra Zeitlhofer, Joanna F Flatt, Tabita M Maia, M Leticia Ribeiro, Bernhard Fahrner, Gerhard Fritsch, Kaan Boztug, Oskar A Haas
We describe the second patient with anionic exchanger 1/band 3 null phenotype (band 3 null(VIENNA) ), which was caused by a novel nonsense mutation c.1430C>A (p.Ser477X) in exon 12 of SLC4A1. We also update on the previous band 3 null(COIMBRA) patient, thereby elucidating the physiological implications of total loss of AE1/band 3. Besides transfusion-dependent severe hemolytic anemia and complete distal renal tubular acidosis, dyserythropoiesis was identified in the band 3 null(VIENNA) patient, suggesting a role for band 3 in erythropoiesis...
October 8, 2016: Pediatric Blood & Cancer
Gaurav Agarwal, Padam Hirachan, Jonathan Gelfond, Paolo Fanti, Claudia Hura, Shweta Bansal
BACKGROUND: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency (VDD) is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effect of oral ergocalciferol supplementation on requirement of erythropoietin (EPO) and active vitamin D analogues, and hospitalization rate in maintenance hemodialysis (HD) patients. METHODS: This retrospective cohort study included 186 patients who were on HD for 3 months and had 25(OH)D levels < 30 ng/ml...
October 7, 2016: BMC Nephrology
Larissa M Williams, Briony A Lago, Andrew G McArthur, Amogelang R Raphenya, Nicholas Pray, Nabil Saleem, Sophia Salas, Katherine Paulson, Roshni S Mangar, Yang Liu, Andy H Vo, Jordan A Shavit
Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants as compared to an adult. In response to pro-oxidant exposure, members of the Cap'n'Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including Nfe2 and Nfe2-related factors, Nrfs) activate the expression of genes whose protein products contribute to reduced toxicity. Here, we studied the role of the CNC protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish (Danio rerio)...
October 1, 2016: Aquatic Toxicology
Michela Asperti, Tanja Stuemler, Maura Poli, Magdalena Gryzik, Lena Lifshitz, Esther G Meyron-Holtz, Israel Vlodavsky, Paolo Arosio
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS)...
2016: PloS One
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