Profound morphological changes in the erythrocytes and fibrin networks of patients with hemochromatosis or with hyperferritinemia, and their normalization by iron chelators and other agents

PLoS ONE

Volumn 9, Issue 1, 2014, Pages

  Pretorius, Etheresia ^a   Bester, Janette ^a   Vermeulen, Natasha ^a   Lipinski, Boguslaw ^b   Gericke, George S ^c   Kell, Douglas B ^d  

^a UNIVERSITY OF PRETORIA   (South Africa)

^b HARVARD MEDICAL SCHOOL   (United States)

^c Ampath National Laboratory Services   (South Africa)

^d UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CLIOQUINOL; DEFEROXAMINE MESYLATE; FIBRIN; IRON; IRON CHELATING AGENT; SALICYLIC ACID; SELENITE; THROMBIN;

ADOLESCENT; ADULT; AGED; ARTICLE; CHILD; CONTROLLED STUDY; ERYTHROCYTE; ERYTHROCYTE STRUCTURE; FEMALE; HEMOCHROMATOSIS; HUMAN; HUMAN CELL; HYPERFERRITINEMIA; IRON CHELATION; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; PROTEIN STRUCTURE; SCANNING ELECTRON MICROSCOPY; SCHOOL CHILD; THROMBOCYTE RICH PLASMA; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; CHILD; CLIOQUINOL; DEFEROXAMINE; ERYTHROCYTES; FEMALE; FERRITINS; FIBRIN; HEMOCHROMATOSIS; HUMANS; HYDROXYL RADICAL; IRON; IRON CHELATING AGENTS; MALE; MICROSCOPY, ELECTRON, SCANNING; MIDDLE AGED; PLATELET-RICH PLASMA; SALICYLIC ACID; SELENIOUS ACID; THROMBIN; UP-REGULATION;

EID: 84897404263     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0085271     Document Type: Article

References (155)

1. Kell DB (2009) Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2: 2.
2. Kell DB (2010) Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 84: 825-889.
3. Crichton RR, Dexter DT, Ward RJ (2011) Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm 118: 301-314.
4. Funke C, Schneider SA, Berg D, Kell DB (2012) Genetics and iron in the systems biology of Parkinson's disease and some related disorders. Neurochem Int.
5. Castellani RJ, Moreira PI, Perry G, Zhu X (2012) The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors 38: 133-138.
6. Camaschella C, Poggiali E (2011) Inherited disorders of iron metabolism. Curr Opin Pediatr 23: 14-20.
7. Pretorius E, Bester J, Vermeulen N, Lipinski B (2013) Oxidation inhibits iron-induced blood coagulation. Curr Drug Targets 14: 13-19.
8. Pretorius E, Vermeulen N, Bester J, Lipinski B, Kell DB (2013) A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy. Toxicol Mech Methods.
9. Finberg KE (2013) Striking the target in iron overload disorders. J Clin Invest 123: 1424-1427.
10. Tsuchiya K, Nitta K (2013) Hepcidin is a potential regulator of iron status in chronic kidney disease. Ther Apher Dial 17: 1-8.
11. Shizukuda Y, Bolan CD, Tripodi DJ, Yau YY, Nguyen TT, et al. (2006) Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis. Am J Cardiol 98: 954-959. (Pubitemid 44402270)
12. Shizukuda Y, Bolan CD, Nguyen TT, Botello G, Tripodi DJ, et al. (2007) Oxidative stress in asymptomatic subjects with hereditary hemochromatosis. Am J Hematol 82: 249-250. (Pubitemid 46363804)
13. Kwan T, Leber B, Ahuja S, Carter R, Gerstein HC (1998) Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene. Clin Invest Med 21: 251-257. (Pubitemid 29086255)
14. Martines AM, Masereeuw R, Tjalsma H, Hoenderop JG, Wetzels JF, et al. (2013) Iron metabolism in the pathogenesis of iron-induced kidney injury. Nat Rev Nephrol.
15. Day SM, Duquaine D, Mundada LV, Menon RG, Khan BV, et al. (2003) Chronic iron administration increases vascular oxidative stress and accelerates arterial thrombosis. Circulation 107: 2601-2606. (Pubitemid 36628943)
16. Ahluwalia N, Genoux A, Ferrieres J, Perret B, Carayol M, et al. (2010) Iron status is associated with carotid atherosclerotic plaques in middle-aged adults. J Nutr 140: 812-816.
17. Depalma RG, Hayes VW, Chow BK, Shamayeva G, May PE, et al. (2010) Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. J Vasc Surg 51: 1498-1503.
18. Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F (1997) Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 96: 3300-3307. (Pubitemid 27513398)
19. Merono T, Rosso LG, Sorroche P, Boero L, Arbelbide J, et al. (2011) High risk of cardiovascular disease in iron overload patients. Eur J Clin Invest 41: 479-486.
20. Nagy E, Eaton JW, Jeney V, Soares MP, Varga Z, et al. (2010) Red cells, hemoglobin, heme, iron, and atherogenesis. Arterioscler Thromb Vasc Biol 30: 1347-1353.
21. Cooper GJS (2011) Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease. Drugs 71: 1281-1320.
22. Simon M, Bourel M, Fauchet R, Genetet B (1976) Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 17: 332-334.
23. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, et al. (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13: 399-408. (Pubitemid 26256612)
24. Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, et al. (2008) Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med 358: 221-230.
25. Clark P, Britton LJ, Powell LW (2010) The diagnosis and management of hereditary haemochromatosis. Clin Biochem Rev 31: 3-8.
26. Gurrin LC, Osborne NJ, Constantine CC, McLaren CE, English DR, et al. (2008) The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis. Gastroenterology 135: 1945-1952.
27. Asberg A, Hveem K, Kannelonning K, Irgens WO (2007) Penetrance of the C28Y/C282Y genotype of the HFE gene. Scand J Gastroenterol 42: 1073-1077. (Pubitemid 47301132)
28. Dhillon BK, Das R, Garewal G, Chawla Y, Dhiman RK, et al. (2007) Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India. World J Gastroenterol 13: 2956-2959. (Pubitemid 47033754)
29. McCune CA, Ravine D, Carter K, Jackson HA, Hutton D, et al. (2006) Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients. Gut 55: 554-562.
30. McLaren GD, Gordeuk VR (2009) Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Hematology Am Soc Hematol Educ Program: 195-206.
31. Weiss G (2010) Genetic mechanisms and modifying factors in hereditary hemochromatosis. Nat Rev Gastroenterol Hepatol 7: 50-58.
32. Swinkels DW, Fleming RE (2011) Novel observations in hereditary hemochromatosis: potential implications for clinical strategies. Haematologica 96: 485-488.
33. Pietrangelo A (2010) Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 139: 393-408, 408 e391-392.
34. Babitt JL, Lin HY (2011) The molecular pathogenesis of hereditary hemochromatosis. Semin Liver Dis 31: 280-292.
35. Tanaka T, Roy CN, Yao W, Matteini A, Semba RD, et al. (2010) A genome-wide association analysis of serum iron concentrations. Blood 115: 94-96.
36. Darshan D, Frazer DM, Anderson GJ (2010) Molecular basis of iron-loading disorders. Expert Rev Mol Med 12: e36.
37. Santos PC, Krieger JE, Pereira AC (2012) Molecular diagnostic and pathogenesis of hereditary hemochromatosis. Int J Mol Sci 13: 1497-1511.
38. McLaren CE, Garner CP, Constantine CC, McLachlan S, Vulpe CD, et al. (2011) Genome-wide association study identifies genetic loci associated with iron deficiency. PLoS ONE 6: e17390.
39. Wang Y, Gurrin LC, Wluka AE, Bertalli NA, Osborne NJ, et al. (2012) HFE C282Y homozygosity is associated with an increased risk of total hip replacement for osteoarthritis. Semin Arthritis Rheum 41: 872-878.
40. Olynyk JK, Trinder D, Ramm GA, Britton RS, Bacon BR (2008) Hereditary hemochromatosis in the post-HFE era. Hepatology 48: 991-1001.
41. Crownover BK, Covey CJ (2013) Hereditary hemochromatosis. Am Fam Physician 87: 183-190.
42. Roetto A, Camaschella C (2005) New insights into iron homeostasis through the study of non-HFE hereditary haemochromatosis. Best Pract Res Clin Haematol 18: 235-250. (Pubitemid 40298367)
43. Vermeulen E, Vermeersch P (2012) Hepcidin as a biomarker for the diagnosis of iron metabolism disorders: a review. Acta Clin Belg 67: 190-197.
44. Ganz T, Nemeth E (2012) Hepcidin and iron homeostasis. Biochim Biophys Acta 1823: 1434-1443.
45. Altes A, Bach V, Ruiz A, Esteve A, Felez J, et al. (2009) Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene. Ann Hematol 88: 951-955.
46. Santos PC, Cancado RD, Pereira AC, Schettert IT, Soares RA, et al. (2011) Hereditary hemochromatosis: mutations in genes involved in iron homeostasis in Brazilian patients. Blood Cells Mol Dis 46: 302-307.
47. Chen J, Enns CA (2012) Hereditary hemochromatosis and transferrin receptor 2. Biochim Biophys Acta 1820: 256-263.
48. Kasvosve I (2013) Effect of ferroportin polymorphism on iron homeostasis and infection. Clin Chim Acta 416: 20-25.
49. Ayonrinde OT, Milward EA, Chua AC, Trinder D, Olynyk JK (2008) Clinical perspectives on hereditary hemochromatosis. Crit Rev Clin Lab Sci 45: 451-484.
50. Bassett ML (2001) Haemochromatosis: iron still matters. Intern Med J 31: 237-242.
51. Acton RT, Barton JC, Passmore LV, Adams PC, Speechley MR, et al. (2006) Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) study. Diabetes Care 29: 2084-2089. (Pubitemid 44871191)
52. Adams PC, Reboussin DM, Barton JC, Acton RT, Speechley M, et al. (2008) Serial serum ferritin measurements in untreated HFE C282Y homozygotes in the Hemochromatosis and Iron Overload Screening Study. Int J Lab Hematol 30: 300-305.
53. Jacobs EM, Hendriks JC, van Deursen CT, Kreeftenberg HG, de Vries RA, et al. (2009) Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study. J Hepatol 50: 174-183.
54. Jomova K, Valko M (2011) Importance of iron chelation in free radical-induced oxidative stress and human disease. Curr Pharm Des 17: 3460-3473.
55. Barton JC, Barton JC, Acton RT, So J, Chan S, et al. (2012) Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 mug/L at diagnosis. Clin Gastroenterol Hepatol 10: 412-416.
56. Prá D, Franke SI, Henriques JA, Fenech M (2012) Iron and genome stability: an update. Mutat Res 733: 92-99.
57. Ferro E, Visalli G, Civa R, La Rosa MA, Randazzo Papa G, et al. (2012) Oxidative damage and genotoxicity biomarkers in transfused and untransfused thalassemic subjects. Free Radic Biol Med 53: 1829-1837.
58. Pretorius E, Vermeulen N, Bester J, Lipinski B (2013) Novel use of scanning electron microscopy for detection of iron-induced morphological changes in human blood. Microsc Res Tech 76: 268-271.
59. Wilson JG, Lindquist JH, Grambow SC, Crook ED, Maher JF (2003) Potential role of increased iron stores in diabetes. Am J Med Sci 325: 332-339. (Pubitemid 36712655)
60. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, et al. (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291: 711-717. (Pubitemid 38543791)
61. Lee DH, Folsom AR, Jacobs DR, Jr. (2004) Dietary iron intake and Type 2 diabetes incidence in postmenopausal women: the Iowa Women's Health Study. Diabetologia 47: 185-194. (Pubitemid 38315354)
62. Rajpathak SN, Wylie-Rosett J, Gunter MJ, Negassa A, Kabat GC, et al. (2009) Biomarkers of body iron stores and risk of developing type 2 diabetes. Diabetes Obes Metab 11: 472-479.
63. Huang J, Jones D, Luo B, Sanderson M, Soto J, et al. (2011) Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes 60: 80-87.
64. Wood MJ, Powell LW, Dixon JL, Ramm GA (2012) Clinical cofactors and hepatic fibrosis in hereditary hemochromatosis: the role of diabetes mellitus. Hepatology 56: 904-911.
65. Moczulski DK, Grzeszczak W, Gawlik B (2001) Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy. Diabetes Care 24: 1187-1191. (Pubitemid 33716396)
66. Pretorius E, Lipinski B (2013) Iron alters red blood cell morphology. Blood 121: 9.
67. Sheetz MP, Singer SJ (1974) Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions. Proc Natl Acad Sci U S A 71: 4457-4461.
68. Wong B (2011) Points of view: the overview figure. Nat Methods 8: 365.
69. Zeitz M, Sens P (2012) Reversibility of red blood cell deformation. Phys Rev E Stat Nonlin Soft Matter Phys 85: 051904.
70. Mangasser-Stephan K, Tag C, Reiser A, Gressner AM (1999) Rapid genotyping of hemochromatosis gene mutations on the LightCycler with fluorescent hybridization probes. Clin Chem 45: 1875-1878. (Pubitemid 29477354)
71. Pretorius E (2008) The role of platelet and fibrin ultrastructure in identifying disease patterns. Pathophysiol Haemost Thromb 36: 251-258.
72. Broadhurst D, Kell DB (2006) Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2: 171-196. (Pubitemid 46099798)
73. Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, et al. (1998) Management of hemochromatosis. Hemochromatosis Management Working Group. Ann Intern Med 129: 932-939.
74. Kellner H, Zoller WG (1992) Repeated isovolemic large-volume erythrocytapheresis in the treatment of idiopathic hemochromatosis. Z Gastroenterol 30: 779-783. (Pubitemid 23008795)
75. Adams P (2008) Management of elevated serum ferritin levels. Gastroenterol Hepatol (N Y) 4: 333-334.
76. Adams PC, Passmore L, Chakrabarti S, Reboussin DM, Acton RT, et al. (2006) Liver diseases in the hemochromatosis and iron overload screening study. Clin Gastroenterol Hepatol 4: 918-923; quiz 807.
77. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, et al. (2005) Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352: 1769-1778. (Pubitemid 40570925)
78. Gordeuk VR, Lovato L, Barton J, Vitolins M, McLaren G, et al. (2012) Dietary iron intake and serum ferritin concentration in 213 patients homozygous for the HFEC282Y hemochromatosis mutation. Can J Gastroenterol 26: 345-349.
79. Koziol JA, Ho NJ, Felitti VJ, Beutler E (2001) Reference centiles for serum ferritin and percentage of transferrin saturation, with application to mutations of the HFE gene. Clin Chem 47: 1804-1810. (Pubitemid 32881193)
80. Waalen J, Felitti VJ, Gelbart T, Beutler E (2008) Screening for hemochromatosis by measuring ferritin levels: a more effective approach. Blood 111: 3373-3376.
81. Brandhagen DJ, Fairbanks VF, Baldus W (2002) Recognition and management of hereditary hemochromatosis. Am Fam Physician 65: 853-860.
82. Limdi JK, Crampton JR (2004) Hereditary haemochromatosis. QJM 97: 315-324. (Pubitemid 38807410)
83. Daniels R (2010) Delmar's Guide to Laboratory and Diagnostic Tests. 2nd Ed.
84. McCullen MA, Crawford DH, Hickman PE (2002) Screening for hemochromatosis. Clin Chim Acta 315: 169-186. (Pubitemid 33145256)
85. Pretorius E, Vermeulen N, Bester J, Lipinski B, Kell DB (2013) A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy. Toxicol Mech Methods 23: 352-359.
86. Azizova OA, Shvachko AG, Aseichev AV (2009) Effect of iron ions on functional activity of thrombin. Bull Exp Biol Med 148: 776-779.
87. Flaten TP, Aaseth J, Andersen O, Kontoghiorghes GJ (2012) Iron mobilization using chelation and phlebotomy. J Trace Elem Med Biol 26: 127-130.
88. Ma Y, Zhou T, Kong X, Hider RC (2012) Chelating agents for the treatment of systemic iron overload. Curr Med Chem 19: 2816-2827.
89. Yu Y, Gutierrez E, Kovacevic Z, Saletta F, Obeidy P, et al. (2012) Iron chelators for the treatment of cancer. Curr Med Chem 19: 2689-2702.
90. Kaur H, Edmonds SE, Blake DR, Halliwell B (1996) Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid. Ann Rheum Dis 55: 915-920. (Pubitemid 26426686)
91. Halliwell BG, J. M C. (2006) Free Radicals in Biology and Medicine. Oxford University Press.
92. Madathil KS, Karuppagounder SS, Mohanakumar KP (2013) Sodium salicylate protects against rotenone-induced parkinsonism in rats. Synapse.
93. Hardy G, Hardy I, Manzanares W (2012) Selenium supplementation in the critically ill. Nutr Clin Pract 27: 21-33.
94. Bao G, Clifton M, Hoette TM, Mori K, Deng SX, et al. (2010) Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol 6: 602-609.
95. Abergel RJ, Warner JA, Shuh DK, Raymond KN (2006) Enterobactin protonation and iron release: structural characterization of the salicylate coordination shift in ferric enterobactin. J Am Chem Soc 128: 8920-8931. (Pubitemid 44061550)
96. Lipinski B, Pretorius E, Oberholzer HM, van der Spuy WJ (2012) Interaction of fibrin with red blood cells: the role of iron. Ultrastruct Pathol 36: 79-84.
97. Rai D, Felmy AR, Moore DA (1995) The solubility product of crystalline ferric selenite hexahydrate and the complexation constant of FeSeO3+. Journal of Solution Chemistry 24: 735-752.
98. Bush AI (2008) Drug development based on the metals hypothesis of Alzheimer's disease. J Alzheimers Dis 15: 223-240.
99. Bareggi SR, Cornelli U (2012) Clioquinol: review of its mechanisms of action and clinical uses in neurodegenerative disorders. CNS Neurosci Ther 18: 41-46.
100. Oyama TM, Ishida S, Okano Y, Seo H, Oyama Y (2012) Clioquinol-induced increase and decrease in the intracellular Zn2+ level in rat thymocytes. Life Sci 91: 1216-1220.
101. Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Seppanen R, et al. (1992) High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation 86: 803-811.
102. Brewer GJ (2007) Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease. Exp Biol Med (Maywood) 232: 323-335.
103. Franchini M, Targher G, Montagnana M, Lippi G (2008) Iron and thrombosis. Ann Hematol 87: 167-173.
104. Altamura S, Muckenthaler MU (2009) Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J Alzheimers Dis 16: 879-895.
105. Lipinski B, Pretorius E (2012) Novel pathway of ironinduced blood coagulation: implications for diabetes mellitus and its complications. Pol Arch Med Wewn 122: 115-122.
106. Núñez MT, Urrutia P, Mena N, Aguirre P, Tapia V, et al. (2012) Iron toxicity in neurodegeneration. Biometals 25: 761-776.
107. Gotz ME, Double K, Gerlach M, Youdim MB, Riederer P (2004) The relevance of iron in the pathogenesis of Parkinson's disease. Ann N Y Acad Sci 1012: 193-208. (Pubitemid 38455479)
108. Schneider SA, Bhatia KP (2012) Syndromes of neurodegeneration with brain iron accumulation. Semin Pediatr Neurol 19: 57-66.
109. Schneider SA, Hardy J, Bhatia KP (2012) Syndromes of neurodegeneration with brain iron accumulation (NBIA): an update on clinical presentations, histological and genetic underpinnings, and treatment considerations. Mov Disord 27: 42-53.
110. Funke C, Schneider SA, Berg D, Kell DB (2013) Genetics and iron in the systems biology of Parkinson's disease and some related disorders. Neurochem Int 62: 637-652.
111. Lipinski B, Pretorius E, Oberholzer HM, Van Der Spuy WJ (2012) Iron enhances generation of fibrin fibers in human blood: Implications for pathogenesis of stroke. Microsc Res Tech 75: 1185-1190.
112. Pretorius E, Lipinski B (2012) Differences in Morphology of Fibrin Clots Induced with Thrombin and Ferric Ions and Its Pathophysiological Consequences. Heart Lung Circ.
113. Barton JC, Bertoli LF, Rothenberg BE (2000) Peripheral blood erythrocyte parameters in hemochromatosis: evidence for increased erythrocyte hemoglobin content. J Lab Clin Med 135: 96-104. (Pubitemid 30042159)
114. Fleming RE, Britton RS, Waheed A, Sly WS, Bacon BR (2005) Pathophysiology of hereditary hemochromatosis. Semin Liver Dis 25: 411-419. (Pubitemid 41741258)
115. Terman A, Brunk UT (2004) Lipofuscin. Int J Biochem Cell Biol 36: 1400-1404. (Pubitemid 38625820)
116. Terman A, Brunk UT (2006) Oxidative stress, accumulation of biological 'garbage', and aging. Antioxid Redox Signal 8: 197-204. (Pubitemid 43324546)
117. Kurz T, Terman A, Gustafsson B, Brunk UT (2008) Lysosomes in iron metabolism, ageing and apoptosis. Histochem Cell Biol 129: 389-406.
118. Double KL, Dedov VN, Fedorow H, Kettle E, Halliday GM, et al. (2008) The comparative biology of neuromelanin and lipofuscin in the human brain. Cell Mol Life Sci 65: 1669-1682.
119. Yamanishi H, Iyama S, Yamaguchi Y, Kanakura Y, Iwatani Y (2002) Relation between iron content of serum ferritin and clinical status factors extracted by factor analysis in patients with hyperferritinemia. Clin Biochem 35: 523-529. (Pubitemid 35462127)
120. Nielsen P, Günther U, Dürken M, Fischer R, Düllmann J (2000) Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance. J Lab Clin Med 135: 413-418.
121. Konz T, Añón Alvarez E, Montes-Bayon M, Sanz-Medel A (2013) Antibody labeling and elemental mass spectrometry (inductively coupled plasma-mass spectrometry) using isotope dilution for highly sensitive ferritin determination and iron-ferritin ratio measurements. Anal Chem 85: 8334-8340.
122. Akoev VR, Shcherbinina SP, Matveev AV, Tarakhovskii Iu S, Deev AA, et al. (1997) [Study of structural transitions in erythrocyte membranes during hereditary hemochromatosis]. Biull Eksp Biol Med 123: 279-284.
123. Buys AV, Van Rooy MJ, Soma P, Van Papendorp D, Lipinski B, et al. (2013) Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study. Cardiovasc Diabetol 12: 25.
124. Mohandas N, Gallagher PG (2008) Red cell membrane: past, present, and future. Blood 112: 3939-3948.
125. Chan MM, Wooden JM, Tsang M, Gilligan DM, Hirenallur SD, et al. (2013) Hematopoietic protein-1 regulates the actin membrane skeleton and membrane stability in murine erythrocytes. PLoS ONE 8: e54902.
126. Girasole M, Dinarelli S, Boumis G (2012) Structure and function in native and pathological erythrocytes: a quantitative view from the nanoscale. Micron 43: 1273-1286.
127. Kozlova EK, Chernysh AM, Moroz VV, Kuzovlev AN (2012) Analysis of nanostructure of red blood cells membranes by space Fourier transform of AFM images. Micron.
128. Pasini EM, Lutz HU, Mann M, Thomas AW (2010) Red blood cell (RBC) membrane proteomics-Part I: Proteomics and RBC physiology. J Proteomics 73: 403-420.
129. Sheetz MP, Painter RG, Singer SJ (1976) Biological membranes as bilayer couples. III. Compensatory shape changes induced in membranes. J Cell Biol 70: 193-203.
130. Sheetz MP, Singer SJ (1976) Equilibrium and kinetic effects of drugs on the shapes of human erythrocytes. J Cell Biol 70: 247-251.
131. Lim HWG, Wortis M, Mukhopadhyay R (2002) Stomatocyte-discocyte-echinocyte sequence of the human red blood cell: evidence for the bilayer-couple hypothesis from membrane mechanics. Proc Natl Acad Sci U S A 99: 16766-16769. (Pubitemid 36034047)
132. Tachev KD, Danov KD, Kralchevsky PA (2004) On the mechanism of stomatocyte-echinocyte transformations of red blood cells: experiment and theoretical model. Colloids Surf B Biointerfaces 34: 123-140. (Pubitemid 38283688)
133. Cahoon L (2009) The curious case of clioquinol. Nat Med 15: 356-359.
134. Ritchie CW, Bush AI, Mackinnon A, Macfarlane S, Mastwyk M, et al. (2003) Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol 60: 1685-1691. (Pubitemid 37521621)
135. White AR, Barnham KJ, Bush AI (2006) Metal homeostasis in Alzheimer's disease. Expert Rev Neurother 6: 711-722. (Pubitemid 43961875)
136. Choi BY, Jang BG, Kim JH, Seo JN, Wu G, et al. (2013) Copper/zinc chelation by clioquinol reduces spinal cord white matter damage and behavioral deficits in a murine MOG-induced multiple sclerosis model. Neurobiol Dis.
137. Mohanakumar KP, Muralikrishnan D, Thomas B (2000) Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res 864: 281-290. (Pubitemid 30235109)
138. Prus E, Fibach E (2010) Effect of iron chelators on labile iron and oxidative status of thalassaemic erythroid cells. Acta Haematol 123: 14-20.
139. Leitman SF, Browning JN, Yau YY, Mason G, Klein HG, et al. (2003) Hemochromatosis subjects as allogeneic blood donors: a prospective study. Transfusion 43: 1538-1544. (Pubitemid 37371823)
140. Luten M, Roerdinkholder-Stoelwinder B, Rombout-Sestrienkova E, de Grip WJ, Bos HJ, et al. (2008) Red cell concentrates of hemochromatosis patients comply with the storage guidelines for transfusion purposes. Transfusion 48: 436-441. (Pubitemid 351294570)
141. Superior Health Council (2013) Acceptance of HFE haemochromatosis gene mutation carriers as blood donors. Brussels: Superior Health Council. SHC publication no 8672.
142. Davey HM, Kell DB (1996) Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses. Microbiol Rev 60: 641-696. (Pubitemid 26415671)
143. Adams RJ (2007) Big strokes in small persons. Arch Neurol 64: 1567-1574.
144. Lee MT, Piomelli S, Granger S, Miller ST, Harkness S, et al. (2006) Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood 108: 847-852. (Pubitemid 44154616)
145. Mazumdar M, Heeney MM, Sox CM, Lieu TA (2007) Preventing stroke among children with sickle cell anemia: an analysis of strategies that involve transcranial Doppler testing and chronic transfusion. Pediatrics 120: e1107-1116. (Pubitemid 47549606)
146. Mirre E, Brousse V, Berteloot L, Lambot-Juhan K, Verlhac S, et al. (2010) Feasibility and efficacy of chronic transfusion for stroke prevention in children with sickle cell disease. Eur J Haematol 84: 259-265.
147. Switzer JA, Hess DC, Nichols FT, Adams RJ (2006) Pathophysiology and treatment of stroke in sickle-cell disease: present and future. Lancet Neurol 5: 501-512.
148. Verduzco LA, Nathan DG (2009) Sickle cell disease and stroke. Blood 114: 5117-5125.
149. Adamkiewicz TV, Abboud MR, Paley C, Olivieri N, Kirby-Allen M, et al. (2009) Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury. Blood 114: 4632-4638.
150. Walter PB, Harmatz P, Vichinsky E (2009) Iron metabolism and iron chelation in sickle cell disease. Acta Haematol 122: 174-183.
151. Inati A, Khoriaty E, Musallam KM (2011) Iron in sickle-cell disease: what have we learned over the years? Pediatr Blood Cancer 56: 182-190.
152. Inati A, Khoriaty E, Musallam KM, Taher AT (2010) Iron chelation therapy for patients with sickle cell disease and iron overload. Am J Hematol 85: 782-786.
153. Inati A, Musallam KM, Wood JC, Taher AT (2010) Iron overload indices rise linearly with transfusion rate in patients with sickle cell disease. Blood 115: 2980-2981; author reply 2981-2982.
154. Raghupathy R, Manwani D, Little JA (2010) Iron overload in sickle cell disease. Adv Hematol 2010: 272940.
155. Smith-Whitley K, Thompson AA (2012) Indications and complications of transfusions in sickle cell disease. Pediatr Blood Cancer 59: 358-364.