Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil

AbstractInvasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil

Pregnancy In Sickle Cell Disease – Do We Know What To Expect?

[No abstract available]365313314Villers, M.S., Jamison, M.G., De Castro, L.M., James, A.H., Morbidity associated with sickle cell disease in pregnancy (2008) Am J Obstet Gynecol, 199 (2), pp. 125.e1-125.e5Brawley, O.W., Cornelius, L.J., Edwards, L.R., Gamble, V.N., Green, B.L., Inturrisi, C., National Institutes of Health Consensus Development Conference statement: Hydroxyurea treatment for sickle cell disease (2008) Ann Intern Med, 148 (12), pp. 932-938Diav-Citrin, O., Hunnisett, L., Sher, G.D., Koren, G., Hydroxyurea use during pregnancy: A case report in sickle cell disease and review of the literature (1999) Am J Hematol, 60 (2), pp. 148-150Ngô, C., Kayem, G., Habibi, A., Benachi, A., Goffinet, F., Galactéros, F., Pregnancy in sickle cell disease: Maternal and fetal outcomes in a population receiving prophylactic partial exchange transfusions (2010) Eur J Obstet Gynecol Reprod Biol, 152 (2), pp. 138-142Koshy, M., Burd, L., Wallace, D., Moawad, A., Baron, J., Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study (1988) N Engl J Med, 319 (22), pp. 1447-1455Gilli, S.C., De Paula, E.V., Biscaro, F.P., Marques, J.F., Costa, F.F., Saad, S.T., Third-trimester erythrocytapheresis in pregnant patients with sickle cell disease (2007) Int J Gynaecol Obstet, 96 (1), pp. 8-11Silva-Pinto, A.C., Ladeira, S.O., Brunetta, D.M., de Santis, G.C., Angulo, I.L., Covas, D.T., Sickle cell disease and pregnancy: Analysis of 34 patients followed at the Regional Blood Center of Ribeirão Preto, Brazil (2014) Rev Bras Hematol Hemoter, 36 (5), pp. 329-33

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

Inflammation, leucocyte and red cell adhesion to the endothelium contribute to the pathogenesis of sickle cell anaemia. Neutrophils appear to be important for vaso-occlusion, however, eosinophils may also participate in this phenomenon. The role of eosinophils in the pathophysiology of sickle cell anaemia (SCA) and the effect of hydroxycarbamide (HC) therapy on the functional properties of these cells are not understood. Patients with SCA and those on HC therapy (SCAHC) were included in the study. SCAHC individuals presented significantly lower absolute numbers of eosinophils than SCA. Furthermore, SCAHC eosinophils demonstrated significantly lower adhesive properties, compared to SCA eosinophils. SCA and SCAHC eosinophils presented greater spontaneous migration when compared with control eosinophils. Baseline eosinophil peroxidase and reactive oxygen species release was higher for SCA individuals than for control individuals, as were plasma levels of eosinophil derived neurotoxin. SCAHC eosinophil degranulation was lower than that of SCA eosinophil degranulation. Eotaxin-1 and RANTES levels were higher in the plasma of SCA and SCAHC individuals, when compared with controls. These data suggest that eosinophils exist in an activated state in SCA and indicate that these cells play a role in the vaso-occlusive process. The exact mechanism by which HC may alter SCA eosinophil properties is not clear.Inflammation, leucocyte and red cell adhesion to the endothelium contribute to the pathogenesis of sickle cell anaemia. Neutrophils appear to be important for vaso-occlusion, however, eosinophils may also participate in this phenomenon. The role of eosino1642286289sem informaçãosem informaçã

Udp-glucuronosyltransferase 1 Gene Promoter Polymorphism Is Associated With Increased Serum Bilirubin Levels And Cholecystectomy In Patients With Sickle Cell Anemia [1]

[No abstract available]642160162Bosma, P.J., Chowdury, J.R., Bakker, C., The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome (1995) N. Engl. J. Med., 333, pp. 1171-1175Monaghan, G., Ryan, M., Seddon, R., Hume, R., Burchell, B., Genetic variation in bilirubin UDP-glucuronosyltranferase gene promoter and Gilbert's syndrome (1996) Lancet, 347, pp. 578-581Clarke, D.J., Moghrabi, N., Monaghan, G., Genetic defects of the UDP-glucuronosyltransferase-1 (GT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias (1997) Clin. Chim. Acta, 266, pp. 63-74Galanello, R., Perseu, L., Melis, M.A., Hyperbilirubinaemia in heterozygotes beta-thalassemia is related to co-inherited Gilbert's syndrome (1997) Br. J. Haematol., 99, pp. 433-436Kaplan, M., Renbaum, P., Levy-Lahad, E., Gilbert's syndrome and glucose-6-phosphate dehydrogenase deficiency: A dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia (1997) Proc. Natl. Acad. Sci. USA, 94, pp. 12128-12132Bancroft, J.D., Kreamer, B., Gourley, G.R., Gilbert's syndrome accelerates development of neonatal jaundice (1998) J. Pediatr., 132, pp. 656-660Miraglia del Giudice, E., Perrotta, S., Nobili, B., Co-inheritance of Gilbert's syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis (HS) (1999) Blood, 94, pp. 2259-2262Akaba, K., Kimura, T., Sasaki, A., Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese (1999) J. Hum. Genet., 44, pp. 22-25Galanello, R., Piras, S., Barella, S., Cholelithiasis and Gilbert's syndrome in homozygotes β-thalassaemia (2001) Br. J. Haematol., 115, pp. 926-928Premawardhena, A., Fisher, C.A., Fathiu, F., Genetic determinants of jaundice and gallstones in haemoglobin E beta thalassemia (2001) Lancet, 357, pp. 1945-1946Gonçalves, M.S., Nechtman, J.F., Figueiredo, M.S., Sickle cell disease in a Brazilian population from São Paulo: A study of the βs haplotypes (1994) Hum. Hered., 44, pp. 322-327Fertrin, K.Y., Gonçalves, M.S., Saad, S.T.O., Costa, F.F., Frequencies of UDP-glucuronosyltransferase 1 (UGT1A1) gene promoter polymorphisms among distinct ethnic groups from Brazil (2002) Am. J. Med. Genet., 108, pp. 117-119Passon, R.G., Howard, T.A., Zimmerman, A.S., Schultz, W.H., Ware, R.E., Influence of bilirubin uridine diphosphate-glucuronosyltransferase 1A promoter polymorphisms on serum bilirubin levels and cholelithiasis in children with sickle cell anemia (2001) Am. J. Pediatr. Hematol. Oncol., 23, pp. 448-451Embury, S.H., Steinberg, M.H., Genetic Modulators of Disease (1994) Sickle Cell Disease - Basic Principles and Clinical Practice, pp. 279-298. , Embury SH, Hebbel RP, Mohandas N, Steinberg MH, eds. 1st edn. New York: Raven PressChui, D.H., Dover, G.J., Sickle cell disease: No longer a single gene disorder (2001) Curr. Opin. Pediatr., 13, pp. 22-2

Hydroxycarbamide Reduces Eosinophil Adhesion And Degranulation In Sickle Cell Anaemia Patients

Inflammation, leucocyte and red cell adhesion to the endothelium contribute to the pathogenesis of sickle cell anaemia. Neutrophils appear to be important for vaso-occlusion, however, eosinophils may also participate in this phenomenon. The role of eosinophils in the pathophysiology of sickle cell anaemia (SCA) and the effect of hydroxycarbamide (HC) therapy on the functional properties of these cells are not understood. Patients with SCA and those on HC therapy (SCAHC) were included in the study. SCAHC individuals presented significantly lower absolute numbers of eosinophils than SCA. Furthermore, SCAHC eosinophils demonstrated significantly lower adhesive properties, compared to SCA eosinophils. SCA and SCAHC eosinophils presented greater spontaneous migration when compared with control eosinophils. Baseline eosinophil peroxidase and reactive oxygen species release was higher for SCA individuals than for control individuals, as were plasma levels of eosinophil derived neurotoxin. SCAHC eosinophil degranulation was lower than that of SCA eosinophil degranulation. Eotaxin-1 and RANTES levels were higher in the plasma of SCA and SCAHC individuals, when compared with controls. These data suggest that eosinophils exist in an activated state in SCA and indicate that these cells play a role in the vaso-occlusive process. The exact mechanism by which HC may alter SCA eosinophil properties is not clear. © 2013 John Wiley & Sons Ltd.1642286295Adamko, D.J., Wu, Y., Gleich, G.J., Lacy, P., Moqbel, R., The induction of eosinophil peroxidase release: improved methods of measurement and stimulation (2004) Journal of Immunological Methods, 291, pp. 101-108Almeida, C.B., Favero, M.E., Pereira-Cunha, F.G., Lorand-Metze, I., Saad, S.T., Costa, F.F., Conran, N., Alterations in cell maturity and serum survival factors may modulate neutrophil numbers in sickle cell disease (2011) Experimental Biology and Medicine, 236, pp. 1239-1246Amer, J., Ghoti, H., Rachmilewitz, E., Koren, A., Levin, C., Fibach, E., Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants (2006) British Journal of Haematology, 132, pp. 108-113Assis, A., Conran, N., Canalli, A.A., Lorand-Metze, I., Saad, S.T., Costa, F.F., Effect of cytokines and chemokines on sickle neutrophil adhesion to fibronectin (2005) Acta Haematologica, 113, pp. 130-136Blanchard, C., Rothenberg, M.E., Biology of the eosinophil (2009) Advances in Immunology, 101, pp. 81-121Boyd, J.H., Macklin, E.A., Strunk, R.C., De-Baun, M.R., Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia (2006) Blood, 108, pp. 2923-2927Bruijnzeel, P., Storz, E., van der Donk, E., Bruijnzeel-Koomen, C., Skin eosinophilia in patients with allergic asthma, patients with nonallergic asthma, and healthy controls. II: 20-Hydroxy-leukotriene B4 is a potent in vivo and in vitro eosinophil chemotactic factor in nonallergic asthma (1993) The Journal of Allergy and Clinical Immunology, 91, pp. 634-642Canalli, A.A., Conran, N., Fattori, A., Saad, S.T., Costa, F.F., Increased adhesive properties of eosinophils in sickle cell disease (2004) Experimental Hematology, 32, pp. 728-734Canalli, A.A., Franco-Penteado, C.F., Traina, F., Saad, S.T., Costa, F.F., Conran, N., Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell disease (2007) European Journal of Haematology, 79, pp. 330-337Canalli, A.A., Proença, R.F., Franco-Penteado, C.F., Traina, F., Sakamoto, T.M., Saad, S.T., Conran, N., Costa, F.F., Participation of Mac-1, LFA-1 and VLA-4 integrins in the in vitro adhesion of sickle cell disease neutrophils to endothelial layers, and reversal of adhesion by simvastatin (2011) Haematologica, 96, pp. 526-533Charache, S., Barton, F.B., Moore, R.D., Terrin, M.L., Steinberg, M.H., Dover, G.J., Ballas, S.K., Orringer, E.P., Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (1996) Medicine (Baltimore), 75, pp. 300-326Chiang, E.Y., Frenette, P.S., Sickle cell vaso-occlusion (2005) Hematology/Oncology Clinics of North America, 19, pp. 771-784Chihara, J., Kakazu, T., Higashimoto, I., Yamamoto, T., Kurachi, D., Nakajima, S., Increased eosinophil oxidative metabolism by treatment with soluble intercellular adhesion molecule-1 (1995) International Archives of Allergy and Immunology, 108, pp. 45-47Chihara, J., Yamada, H., Yamamoto, T., Kurachi, D., Hayashi-Kameda, N., Honda, K., Kayaba, H., Urayama, O., Priming effect of RANTES on eosinophil oxidative metabolism (1998) Allergy, 53, pp. 1178-1182Conran, N., Saad, S.T., Costa, F.F., Ikuta, T., Leukocyte numbers correlate with plasma levels of granulocyte-macrophage colony-stimulating factor in sickle cell disease (2007) Annals of Hematology, 86, pp. 255-261Costa, G.G., Silva, R.M., Franco-Penteado, C.F., Antunes, E., Ferreira, H.H., Interactions between eotaxin and interleukin-5 in the chemotaxis of primed and non-primed human eosinophils (2007) European Journal of Pharmacology, 566, pp. 200-205Dhalla, N.S., Temsah, R.M., Netticadan, T., Role of oxidative stress in cardiovascular diseases (2000) Journal of Hypertension, 18, pp. 655-673Ekeke, G.I., Sickle cell disease: some haematological changes in steady state and crisis (1987) Biomedica Biochimica Acta, 46, pp. 197-201Elsner, J., Petering, H., Höchstetter, R., Kimmig, D., Wells, T.N., Kapp, A., Proudfoot, A.E., The CC chemokine antagonist Met-RANTES inhibits eosinophil effector functions through the chemokine receptors CCR1 and CCR3 (1997) European Journal of Immunology, 27, pp. 2892-2898Elsner, J., Petering, H., Kimmig, D., Wells, T.N., Proudfoot, A.E., Kapp, A., The CC chemokine receptor antagonist met- RANTES inhibits eosinophil effector functions (1999) International Archives of Allergy and Immunology, 118, pp. 462-465Elsner, J., Dulkys, Y., Gupta, S., Escher, S.E., Forssmann, W.G., Kapp, A., Forssmann, U., Differential pattern of CCR1 internalization in human eosinophils: prolonged internalization by CCL5 in contrast to CCL3 (2005) Allergy, 60, pp. 1386-1393Ferreira, H.H., Lodo, M.L., Martins, A.R., Kandratavicius, L., Salaroli, A.F., Conran, N., Antunes, E., De Nucci, G., Expression of nitric oxide synthases and in vitro migration of eosinophils from allergic rhinitis subjects (2002) European Journal of Pharmacology, 442, pp. 155-162Field, J.J., Horst, J., Strunk, R.C., White, F.V., DeBaun, M.R., Death due to asthma in two adolescents with sickle cell disease (2011) Pediatric Blood & Cancer, 56, pp. 454-457Gleich, G.J., Adolphson, C.R., The eosinophilic leukocyte: structure and function (1986) Advances in Immunology, 39, pp. 177-253Hansel, T.T., De Vries, I.J., Iff, T., Rihs, S., Wandzilak, M., Betz, S., Blaser, K., Walker, C., An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils (1991) Journal of Immunological Methods, 145, pp. 105-110Hassan, H., Mughal, I., Dar, J., Al Mekki, T.E., Chapunduka, Z., Haddad, A., Hassan, I.S., Significant bronchospasm during sickle cell painful crises is associated with a lower peripheral eosinophil count (2006) Respirology, 11, pp. 633-637Hofstra, T.C., Kalra, V.K., Meiselman, H.J., Coates, T.D., Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst (1996) Blood, 87, pp. 4440-4447Holtzclaw, J.D., Jack, D., Aguayo, S.M., Eckman, J.R., Roman, J., Hsu, L.L., Enhanced pulmonary and systemic response to endotoxin in transgenic sickle mice (2004) American Journal of Respiratory and Critical Care Medicine, 169, pp. 687-695Honda, K., Chihara, J., Eosinophil activation by eotaxin primes the production of reactive oxygen species from eosinophils (1999) Allergy, 54, pp. 1262-1269Horie, S., Okubo, Y., Hossain, M., Sato, E., Nomura, H., Koyama, S., Suzuki, J., Sekiguchi, M., Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis (1997) Internal Medicine, 36, pp. 179-185Kim, K.W., Lee, K.E., Kim, E.S., Song, T.W., Sohn, M.H., Kim, K.E., Serum eosinophil-derived neurotoxin (EDN) in diagnosis and evaluation of severity and bronchial hyperresponsiveness in childhood asthma (2007) Lung, 185, pp. 97-103Kinney, T.R., Helms, R.W., O'Branski, E.E., Ohene-Frempong, K., Wang, W., Daeschner, C., Vichinsky, E., Ware, R.E., Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. 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(1996) The Journal of Allergy and Clinical Immunology, 97, pp. 889-892Klings, E.S., Farber, H.W., Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease (2001) Respiratory Research, 2, pp. 280-285Knight-Madden, J.M., Forrester, T.S., Lewis, N.A., Greenough, A., Asthma in children with sickle cell disease and its association with acute chest syndrome (2005) Thorax, 60, pp. 206-210Kroegel, C., Yukawa, T., Dent, G., Venge, P., Chung, K.F., Barnes, P.J., Stimulation of degranulation from human eosinophils by platelet-activating factor (1989) The Journal of Immunology, 142, pp. 3518-3526Kuijpers, T.W., Hoogerwerf, M., van der Laan, L.J., Nagel, G., van der Schoot, C.E., Grunert, F., Roos, D., CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells (1992) The Journal of Cell Biology, 118, pp. 457-466Lanaro, C., Franco-Penteado, C.F., Albuquerque, D.M., Saad, S.T., Conran, N., Costa, F.F., Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy (2009) Journal of Leukocyte Biology, 85, pp. 235-242Logan, M.R., Odemuyiwa, S.O., Moqbel, R., Understanding exocytosis in immune and inflammatory cells: the molecular basis of mediator secretion (2003) The Journal of Allergy and Clinical Immunology, 111, pp. 923-932Mohamed, A.O., Hashim, M.S., Nilsson, U.R., Venge, P., Increased in vivo activation of neutrophils and complement in sickle cell disease (1993) American Journal of Tropical Medicine and Hygiene, 49, pp. 799-803Morris, C.R., Asthma management: reinventing the wheel in sickle cell disease (2009) American Journal of Hematology, 84, pp. 234-241Morris, C.R., Role of arginase in sickle cell lung disease and hemolytic anemias (2010) The Open Nitric Oxide Journal, 2, pp. 41-54Moser, R., Fehr, J., Bruijnzeel, P.L., IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals (1992) The Journal of Immunology, 149, pp. 1432-1438Nagata, M., Sedgwick, J.B., Bates, M.E., Kita, H., Busse, W.W., Eosinophil adhesion to vascular cell adhesion molecule activates superoxide anion generation (1995) The Journal of Immunology, 155, pp. 2194-2202Nandedkar, S.D., Feroah, T.R., Hutchins, W., Weihrauch, D., Konduri, K.S., Wang, J., Strunk, R.C., Pritchard, K.A., Histopathology of experimentally induced asthma in a murine model of sickle cell disease (2008) Blood, 112, pp. 2529-2538Newaskar, M., Hardy, K.A., Morris, C.R., Asthma in sickle cell disease (2011) Scientific World Journal, 26, pp. 1138-1152Nordness, M.E., Lynn, J., Zacharisen, M.C., Scott, P.J., Kelly, K.J., Asthma is a risk factor for acute chest syndrome and cerebral vascular accidents in children with sickle cell disease (2005) Clininical and Molecular Allergy: CMA, 3, p. 2Oh, S.O., Ibe, B.O., Johnson, C., Kurantsin-Mills, J., Raj, J.U., Platelet-activating factor in plasma of patients with sickle cell disease in steady state (1997) Journal of Laboratory and Clinical Medicine, 130, pp. 191-196Phillips, R.M., Stubbs, V.E., Henson, M.R., Williams, T.J., Pease, J.E., Sabroe, I., Variations in eosinophil chemokine responses: an investigation of CCR1 and CCR3 function, expression in atopy, and identification of a functional CCR1 promoter (2003) The Journal of Immunology, 170, pp. 6190-6201Ponath, P.D., Qin, S., Ringler, D.J., Clark-Lewis, I., Wang, J., Kassam, N., Smith, H., Mackay, C.R., Cloning of the human eosinophil chemoattractant, eotaxin. 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Multicenter Study of Hydroxyurea (1997) Blood, 89, pp. 1078-1088Stocks, S.C., Ruchaud-Sparagano, M.H., Kerr, M.A., Grunert, F., Haslett, C., Dransfield, I., CD66: role in the regulation of neutrophil effector function (1996) European Journal of Immunology, 26, pp. 2924-2932Sylvester, K.P., Patey, R.A., Broughton, S., Rafferty, G.F., Rees, D., Thein, S.L., Greenough, A., Temporal relationship of asthma to acute chest syndrome in sickle cell disease (2007) Pediatric Pulmonology, 42, pp. 103-106Walter, P.B., Fung, E.B., Killilea, D.W., Jiang, Q., Hudes, M., Madden, J., Porter, J., Harmatz, P., Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease (2006) British Journal of Haematology, 135, pp. 254-263Warringa, R.A., Schweizer, R.C., Maikoe, T., Kuijper, P.H., Bruijnzeel, P.L., Koendermann, L., Modulation of eosinophil chemotaxis by interleukin-5 (1992) American Journal of Respiratory and Cell Molecular Biology, 7, pp. 631-636Williams, T.J., Jose, P.J., Role of eotaxin and related CC chemokines in allergy and asthma (2000) Chemical Immunology, 78, pp. 166-177Yoon, J., Terada, A., Kita, H., CD66b regulates adhesion and activation of human eosinophils (2007) The Journal of Immunology, 179, pp. 8454-8462Zimmermann, N., King, N.E., Laporte, J., Yang, M., Mishra, A., Pope, S.M., Muntel, E.E., Rothenberg, M.E., Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis (2003) Journal of Clinical Investigation, 111, pp. 1863-187

A chip calorimetry-based method for the real-time investigation of metabolic activity changes in human erythrocytes caused by cell sickling

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOA new calorimetric technique is described which allows the measurement of metabolic heat rates in biological materials which are triggered by changes in the oxygen tension. It uses the high permeability for oxygen of a thin-walled Teflon flow channel of a136771781FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2014/00984-3The authors are indebted to FAPESP – Fundação de Amparo à Pesquisa do Estado de São Paulo, Brasil for financial support (2014/00984-3) and Hematology and Hemotherapy Center –Hemocentro Campinas for supplying the samples. We would like to thank Dominique

Thalassemia Major Phenotypes Secondary To The Association Of β 5′utr +20(c→t) Allele With β 39(c→t)

[No abstract available]893273275Ho, P.J., Rochette, J., Fisher, C.A., Wonke, B., Jarvis, M.K., Yardumian, A., Thein, S.L., Moderate reduction of beta-globin gene transcript by a novel mutation in the 5′ untranslated region: a study of its interaction with other genotypes in two families (1996) Blood, 87, pp. 1170-1178Lewis, B.A., Kim, T.K., Orkin, S.H., A downstream element in the human beta-globin promoter: evidence of extended sequence-specific transcription factor IID contacts (2000) Proc Natl Acad Sci U S A, 97, pp. 7172-7177Sgourou, A., Routledge, S., Antoniou, M., Papachatzopoulou, A., Psiouri, L., Athanassiadou, A., Thalassaemia mutations within the 5′UTR of the human beta-globin gene disrupt transcription (2004) Br J Haematol, 124, pp. 828-835Rossetti, L.C., Targovnik, H.M., Varela, V., The molecular basis of beta-thalassemia in Argentina. Influence of the pattern of immigration from the Mediterranean Basin (2004) Haematologica, 89, pp. 746-747Talmaci, R., Traeger-Synodinos, J., Kanavakis, E., Coriu, D., Colita, D., Gavrila, L., Scanning of beta-globin gene for identification of beta-thalassemia mutation in Romanian population (2004) J Cell Mol Med, 8, pp. 232-240Yavarian, M., Harteveld, C.L., Batelaan, D., Bernini, L.F., Giordano, P.C., Molecular spectrum of beta-thalassemia in the Iranian Province of Hormozgan (2001) Hemoglobin, 25, pp. 35-43Orkin, S.H., Kazazian Jr., H.H., Antonarakis, S.E., Goff, S.C., Boehm, C.D., Sexton, J.P., Waber, P.G., Giardina, P.J., Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster (1982) Nature, 296, pp. 627-631Halvorsen, M., Martin, J.S., Broadaway, S., Laederach, A., Disease-associated mutations that alter the RNA structural ensemble (2010) PLoS Genet, 6, pp. e1001074Leach, K.M., Vieira, K.F., Kang, S.L., Aslanian, A., Teichmann, M., Roeder, R.G., Bungert, J., Characterization of the human β-globin downstream promoter region (2003) Nucleic Acids Res, 31, pp. 1292-1301Reichert, V.C., de Castro, S.M., Wagner, S.C., de Albuquerque, D.M., Hutz, M.H., Leistner-Segal, S., Identification of beta thalassemia mutations in South Brazilians (2008) Ann Hematol, 87, pp. 381-384Pirastu, M., Galanello, R., Doherty, M.A., Tuveri, T., Cao, A., Kan, Y.W., The same β-globin gene mutation is present on nine different β-thalassemia chromosomes in a Sardinian population (1987) Proc Nat Acad Sci USA, 84, pp. 2882-2885Smith, R.A., Ho, P.J., Clegg, J.B., Kidd, J.R., Thein, S.L., Recombination breakpoints in the human β-globin gene cluster (1998) Blood, 92, pp. 4415-442

Increased Circulating Pedf And Low Sicam-1 Are Associated With Sickle Cell Retinopathy

Sickle cell retinopathy (SCR) develops in up to 30% of sickle cell disease patients (SCD) during the second decade of life. Treatment for this affection remains palliative, so studies on its pathophysiology may contribute to the future development of novel therapies. SCR is more frequently observed in hemoglobin SC disease and derives from vaso-occlusion in the microvasculature of the retina leading to neovascularization and, eventually, to blindness. Circulating inflammatory cytokines, angiogenic factors, and their interaction may contribute to the pathophysiology of this complication. Angiopoietin (Ang)-1, Ang-2, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM)-1, E-selectin, P-selectin, IL1-β, TNF-α, pigment epithelium derived factor (PEDF) and vascular endothelial growth factor plasmatic levels were determined in 37 SCD patients with retinopathy, 34 without retinopathy, and healthy controls. We observed that sICAM-1 is significantly decreased, whereas PEDF is elevated in HbSC patients with retinopathy (P = 0.012 and P = 0.031, respectively). Ang-1, Ang-2 and IL1-β levels were elevated in SCD patients (P = 0.001, P < 0.001 and P = 0.001, respectively), compared to controls, and HbSS patients presented higher levels of Ang-2 compared to HbSC (P < 0.001). Our study supports the possible influence of sICAM-1 and PEDF on the pathophysiology of retinal neovascularization in SCD patients. © 2014 Elsevier Inc. All rights reserved

Brazilian Thalassemia Association Protocol For Iron Chelation Therapy In Patients Under Regular Transfusion

In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.356428434Borgna-Pignatti, C., Rugolotto, S., de Stefano, P., Zhao, H., Cappellini, M.D., Del Vecchio, G.C., Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine (2004) Haematologica, 89 (10), pp. 1187-1193. , Comment in: Haematologica. 2004;89(10):1157-9Cunningham, M.J., Macklin, E.A., Neufeld, E.J., Cohen, A.R., Thalassemia Clinical Research Network. Complications of beta-thalassemia major in North America (2004) Blood, 104 (1), pp. 34-39Kirk, P., Roughton, M., Porter, J.B., Walker, J.M., Tanner, M.A., Patel, J., Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major (2009) Circulation, 120 (20), pp. 1961-1968. , Comment in: Circulation. 2009;120(20):1937-9Brittenham, G.M., Griffith, P.M., Nienhuis, A.W., McLaren, C.E., Young, N.S., Tucker, E.E., Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major (1994) N Engl J Med, 331 (9), pp. 567-573. , Comment in: N Engl J Med. 1995;332(4):270-1. N Engl J Med. 1995;332(4):271-2. N Engl J Med. 1994;331(9):609-10Olivieri, N.F., Nathan, D.G., Macmillan, J.H., Wayne, A.S., Liu, P.P., McGee, A., Survival in medically treated patients with homozygous beta-thalassemia (1994) N Engl J Med, 331 (9), pp. 574-578. , Comment in: N Engl J Med. 1995;332(4):271author reply 272-3N Engl J Med. 1995;332(4):271-2author reply 272-3N Engl J Med. 1994331(9):609-10Gabutti, V., Piga, A., Results of long-term iron-chelating therapy (1996) Acta Haematol, 95 (1), pp. 26-36Modell, B., Khan, M., Darlison, M., Survival in beta-thalassaemia major in the UK: Data from the UK Thalassaemia Register (2000) Lancet, 355 (9220), pp. 2051-2052Anderson, L.J., Westwood, M.A., Prescott, E., Walker, J.M., Pennell, D.J., Wonke, B., Development of thalassaemic iron overload cardiomyopathy despite low liver iron levels and meticulous compliance to desferrioxamine (2006) Acta Haematol, 115 (1-2), pp. 106-108Hoffbrand, A.V., Cohen, A., Hershko, C., Role of deferiprone in chelation therapy for transfusional iron overload (2003) Blood, 102 (1), pp. 17-24Victor Hoffbrand, A., Deferiprone therapy for transfusional iron overload (2005) Best Pract Res Clin Haematol, 18 (2), pp. 299-317Wonke, B., Wright, C., Hoffbrand, A.V., Combined therapy with deferiprone and desferrioxamine (1998) Br J Haematol, 103 (2), pp. 361-364. , Comment in: Br J Haematol. 1999;106(1):252-3Mourad, F.H., Hoffbrand, A.V., Sheikh-Taha, M., Koussa, S., Khoriaty, A.I., Taher, A., Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients (2003) Br J Haematol, 121 (1), pp. 187-189Kattamis, A., Kassou, C., Berdousi, H., Ladis, V., Papassotiriou, I., Kattamis, C., Combined therapy with desferrioxamine and deferiprone in thalassemic patients: Effect on urinary iron excretion (2003) Haematologica, 88 (12), pp. 1423-1425Wu, K.H., Chang, J.S., Tsai, C.H., Peng, C.T., Combined therapy with deferiprone and desferrioxamine successfully regresses severe heart failure in patients with beta-thalassemia major (2004) Ann Hematol, 83 (7), pp. 471-473Alymara, V., Bourantas, D., Chaidos, A., Bouranta, P., Gouva, M., Vassou, A., Effectiveness and safety of combined iron-chelation therapy with deferoxamine and deferiprone (2004) Hematol J, 5 (6), pp. 475-479Origa, R., Bina, P., Agus, A., Crobu, G., Defraia, E., Dessi, C., Combined therapy with deferiprone and desferrioxamine in thalassemia major (2005) Haematologica, 90 (10), pp. 1309-1314. , Comment in: Haematologica. 2005;90(10):1297ADaar, S., Pathare, A.V., Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload (2006) Ann Hematol, 85 (5), pp. 315-319Kattamis, A., Ladis, V., Berdousi, H., Kelekis, N.L., Alexopoulou, E., Papasotiriou, I., Iron chelation treatment with combined therapy with deferiprone and deferioxamine: A 12-month trial (2006) Blood Cells Mol Dis, 36 (1), pp. 21-25Piga, A., Gaglioti, C., Fogliacco, E., Tricta, F., Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: A retrospective analysis (2003) Haematologica, 88 (5), pp. 489-496. , Comment in: Haematologica. 2003;88(5):481-2Borgna-Pignatti, C., Cappellini, M.D., de Stefano, P., Del Vecchio, G.C., Forni, G.L., Gamberini, M.R., Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major (2006) Blood, 107 (9), pp. 3733-3737Pennell, D.J., Berdoukas, V., Karagiorga, M., Ladis, V., Piga, A., Aessopos, A., Randomized controlled trial of deferiprone or desferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis (2006) Blood, 107 (9), pp. 3738-3744Tanner, M.A., Galanello, R., Dessi, C., Smith, G.C., Westwood, M.A., Agus, A., A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance (2007) Circulation, 115 (14), pp. 1876-1884Tsironi, M., Deftereos, S., Andriopoulos, P., Farmakis, D., Meletis, J., Aessopos, A., Reversal of heart failure in thalassemia major by combined chelation therapy: A case report (2005) Eur J Haematol, 74 (1), pp. 84-85Davis, B.A., Porter, J.B., Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia (2000) Blood, 95 (4), pp. 1229-1236Neufeld, E.J., Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: New data, new questions (2006) Blood, 107 (9), pp. 3436-3441Cappellini, M.D., Cohen, A., Piga, A., Bejaoui, M., Perrotta, S., Agaoglu, L., A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia (2006) Blood, 107 (9), pp. 3455-3462. , Comment in: Blood. 2006;108(5):1775-6Blood. 2006;108(2):774-5Blood. 2006;108(2):778Deugnier, Y., Turlin, B., Ropert, M., Cappellini, M.D., 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J.B., Cappellini, M.D., Chan, L.L., El-Beshlawy, A., Aydinok, Y., Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload (2011) Haematologica, 96 (1), pp. 48-54. , Comment in: Haematologica. 2011;96(1):5-8Pennell, D.J., Porter, J.B., Cappellini, M.D., Chan, L.L., El-Beshlawy, A., Aydinok, Y., Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major (2012) Haematologica, 97 (6), pp. 842-848De Assis, R.A., Ribeiro, A.A., Kay, F.U., Rosemberg, L.A., Nomura, C.H., Loggetto, S.R., Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients (2012) Eur J Radiol, 81 (7), pp. 1465-1470Wood, J.C., Tyszka, J.M., Carson, S., Nelson, M.D., Coates, T.D., Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease (2004) Blood, 103 (5), pp. 1934-1936Wood, J.C., Origa, R., Agus, A., Matta, G., Coates, 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