An efficient protocol for the generation of monocyte derived dendritic cells using serum-free media for clinical applications in post remission aml patients

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on "good manufacture practices" (GM442180188sem informaçãosem informaçã

Autologous platelet gel: five cases illustrating use on sickle cell disease ulcers

Leg ulcers represent a particularly disabling complication in patients with sickle cell disease (SCD). Platelet gel (PG) is a novel therapeutic strategy used for accelerating wound healing of a wide range of tissues through the continuous release of platelet growth factors. Here, we describe the use of PG preparation according to Anitua's PRGF (preparations rich in growth factors) protocol for treating chronic nonhealing ulcers in patients with SCD. A positive response occurred in 3 patients with an area reduction of 85.7% to 100%, which occurred within 7 to 10 weeks, and a 35.2% and 20.5% of area reduction in 2 other patients, who however, had large ulcers. After calcium chloride addition, the platelet-rich plasmas demonstrated enhanced platelet-derived growth factors-BB (P < .001), transforming growth factor-β1 (P = .015), vascular endothelial growth factors (P = .03), and hepatocyte growth factors (nonsignificant) secretion. Furthermore, calcium chloride addition induced a significant decrease in platelet number (P = .0134) and there was no leukocyte detection in the PG product. These results demonstrate that PG treatment might impact the healing of leg ulcers in sickle cell disease, especially in patients with small ulcers.Leg ulcers represent a particularly disabling complication in patients with sickle cell disease (SCD). Platelet gel (PG) is a novel therapeutic strategy used for accelerating wound healing of a wide range of tissues through the continuous release of plate132120126sem informaçãosem informaçã

Obesity And Inflammation And The Effect On The Hematopoietic System

Bone marrow is organized in specialized microenvironments known as 'marrow niches'. These are important for the maintenance of stem cells and their hematopoietic progenitors whose homeostasis also depends on other cell types present in the tissue. Extrinsic factors, such as infection and inflammatory states, may affect this system by causing cytokine dysregulation (imbalance in cytokine production) and changes in cell proliferation and self-renewal rates, and may also induce changes in the metabolism and cell cycle. Known to relate to chronic inflammation, obesity is responsible for systemic changes that are best studied in the cardiovascular system. Little is known regarding the changes in the hematopoietic system induced by the inflammatory state carried by obesity or the cell and molecular mechanisms involved. The understanding of the biological behavior of hematopoietic stem cells under obesity-induced chronic inflammation could help elucidate the pathophysiological mechanisms involved in other inflammatory processes, such as neoplastic diseases and bone marrow failure syndromes. © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. All rights reserved.362147151Molofsky, A.V., Pardal, R., Morrison, S.J., Diverse mechanisms regulate stem cell self-renewal (2004) Curr Opin Cell Biol, 16, pp. 700-707Morrison, S.J., Spradling, A.C., Stem cells and niches: Mechanisms that promote stem cell maintenance throughout life (2008) Cell, 132, pp. 598-611Yamazaki, S., Iwama, A., Takayanagi, S., Eto, K., Ema, H., Nakauchi, H., TGF-beta as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation (2009) Blood, 113, pp. 1250-1256Wilson, A., Laurenti, E., Oser, G., van der Wath, R.C., Blanco-Bose, W., Jaworski, M., Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair (2008) Cell, 135, pp. 1118-1129Omatsu, Y., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno, K., The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche (2010) Immunity, 33, pp. 387-399Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche (2004) Cell, 118, pp. 149-161Zipori, D., Duksin, D., Tamir, M., Argaman, A., Toledo, J., Malik, Z., Cultured mouse marrow stromal cell lines. II. Distinct subtypes differing in morphology, collagen types, myelopoietic factors, and leukemic cell growth modulating activities (1985) J Cell Physiol, 122, pp. 81-90Zhang, J., Niu, C., Ye, L., Huang, H., He, X., Tong, W.G., Identification of the haematopoietic stem cell niche and control of the niche size (2003) Nature, 425, pp. 836-841Kiel, M.J., Yilmaz, O.H., Iwashita, T., Terhorst, C., Morrison, S.J., SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells (2005) Cell, 121, pp. 1109-1121Sugiyama, T., Kohara, H., Noda, M., Nagasawa, T., Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches (2006) Immunity, 25, pp. 977-988Nagasawa, T., The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche (2007) Adv Exp Med Biol, 602, pp. 69-75Hayashi, S., Yamada, T., Tsuneto, M., Yamane, T., Takahashi, M., Shultz, L.D., Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-alpha (2003) J Immunol, 171, pp. 5130-5139Christopher, M.J., Liu, F., Hilton, M.J., Long, F., Link, D.C., Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization (2009) Blood, 114, pp. 1331-1339Chen, C., Liu, Y., Zheng, P., Mammalian target of rapamycin activation underlies HSC defects in autoimmune disease and inflammation in mice (2010) J Clin Invest, 120, pp. 4091-4101Baldridge, M.T., King, K.Y., Boles, N.C., Weksberg, D.C., Goodell, M.A., Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection (2010) Nature, 465, pp. 793-797Zeng, W., Miyazato, A., Chen, G., Kajigaya, S., Young, N.S., Maciejewski, J.P., Interferon-gamma-induced gene expression in CD34 cells: Identification of pathologic cytokine-specific signature profiles (2006) Blood, 107, pp. 167-175Selleri, C., Sato, T., Anderson, S., Young, N.S., Maciejewski, J.P., Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death (1995) J Cell Physiol, 165, pp. 538-546Ferrante Jr., A.W., Obesity-induced inflammation: A metabolic dialogue in the language of inflammation (2007) J Intern Med, 262, pp. 408-414Hevener, A.L., Febbraio, M.A., The 2009 stock conference report: Inflammation, obesity and metabolic disease (2010) Obes Rev, 11, pp. 635-644Hotamisligil, G.S., Inflammation and metabolic disorders (2006) Nature, 444, pp. 860-867Bluher, M., The distinction of metabolically'healthy' from'unhealthy' obese individuals (2010) Curr Opin Lipidol, 21, pp. 38-43Cortez, M., Carmo, L.S., Rogero, M.M., Borelli, P., Fock, R.A., A high-fat diet increases IL-1, IL-6, and TNF-alpha production by increasing NF-kappaB and attenuating PPAR-gamma expression in bone marrow mesenchymal stem cells (2013) Inflammation, 36, pp. 379-386do Carmo, L.S., Rogero, M.M., Paredes-Gamero, E.J., Nogueira-Pedro, A., Xavier, J.G., Cortez, M., A high-fat diet increases interleukin-3 and granulocyte colony-stimulating factor production by bone marrow cells and triggers bone marrow hyperplasia and neutrophilia in Wistar rats (2013) Exp Biol Med (Maywood), 238, pp. 375-384Nanji, A.A., Freeman, J.B., Relationship between body weight and total leukocyte count in morbid obesity (1985) Am J Clin Pathol, 84, pp. 346-347Pratley, R.E., Wilson, C., Bogardus, C., Relation of the white blood cell count to obesity and insulin resistance: Effect of race and gender (1995) Obes Res, 3, pp. 563-571Yanoff, L.B., Menzie, C.M., Denkinger, B., Sebring, N.G., McHugh, T., Remaley, A.T., Inflammation and iron deficiency in the hypoferremia of obesity (2007) Int J Obes (Lond), 31, pp. 1412-1429Vuppalanchi, R., Troutt, J.S., Konrad, R.J., Ghabril, M., Saxena, R., Bell, L.N., Serum hepcidin levels are associated with obesity but not liver disease (2014) Obesity (Silver Spring), 22, pp. 836-841Chung, B., Matak, P., McKie, A.T., Sharp, P., Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells (2007) J Nutr, 137, pp. 2366-2370Ganz, T., Hepcidin--a regulator of intestinal iron absorption and iron recycling by macrophages (2005) Best Pract Res Clin Haematol, 18, pp. 171-182Chen, M., Krishnamurthy, A., Mohamed, A.R., Green, R., Hematological disorders following gastric bypass surgery: Emerging concepts of the interplay between nutritional deficiency and inflammation (2013) Biomed Res Int, 2013, p. 205467von Drygalski, A., Andris, D.A., Nuttleman, P.R., Jackson, S., Klein, J., Wallace, J.R., Anemia after bariatric surgery cannot be explained by iron deficiency alone: Results of a large cohort study (2011) Surg Obes Relat Dis, 7, pp. 151-156Dallal, R.M., Leighton, J., Trang, A., Analysis of leukopenia and anemia after gastric bypass surgery (2012) Surg Obes Relat Dis, 8, pp. 164-168Parmar, K., Mauch, P., Vergilio, J.A., Sackstein, R., Down, J.D., Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia (2007) Proc Natl Acad Sci U S A, 104, pp. 5431-5436Danet, G.H., Pan, Y., Luongo, J.L., Bonnet, D.A., Simon, M.C., Expansion of human SCID-repopulating cells under hypoxic conditions (2003) J Clin Invest, 112, pp. 126-135Eliasson, P., Jonsson, J.I., The hematopoietic stem cell niche: Low in oxygen but a nice place to be (2010) J Cell Physiol, 222, pp. 17-22Simsek, T., Kocabas, F., Zheng, J., Deberardinis, R.J., Mahmoud, A.I., Olson, E.N., The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche (2010) Cell Stem Cell, 7, pp. 380-390Patten, D.A., Germain, M., Kelly, M.A., Slack, R.S., Reactive oxygen species: Stuck in the middle of neurodegeneration (2010) J Alzheimers Dis, 20 (SUPPL. 2), pp. S357-S367Ando, K., Fujita, T., Metabolic syndrome and oxidative stress (2009) Free Radic Biol Med, 47, pp. 213-218Jang, Y.Y., Sharkis, S.J., A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche (2007) Blood, 110, pp. 3056-3063Warburg, O., On respiratory impairment in cancer cells (1956) Science, 124, pp. 269-270Deberardinis, R.J., Lum, J.J., Hatzivassiliou, G., Thompson, C.B., The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation (2008) Cell Metab, 7, pp. 11-20Gatenby, R.A., Gillies, R.J., Why do cancers have high aerobic glycolysis? (2004) Nat Rev Cancer, 4, pp. 891-899Almeida, A., Moncada, S., Bolanos, J.P., Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway (2004) Nat Cell Biol, 6, pp. 45-51Motoshima, H., Goldstein, B.J., Igata, M., Araki, E., AMPK and cell proliferation--AMPK as a therapeutic target for atherosclerosis and cancer (2006) J Physiol, 574 (PART 1), pp. 63-71Marsin, A.S., Bertrand, L., Rider, M.H., Deprez, J., Beauloye, C., Vincent, M.F., Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia (2000) Curr Biol, 10, pp. 1247-1255Wang, G.L., Jiang, B.H., Rue, E.A., Semenza, G.L., Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension (1995) Proc Natl Acad Sci U S A, 92, pp. 5510-5514Semenza, G.L., Hypoxia-inducible factor 1: Regulator of mitochondrial metabolism and mediator of ischemic preconditioning (2011) Biochim Biophys Acta, 1813, pp. 1263-126

Human T-celllymphotropic Virus Type L Transac1tvator Tax And Transcription Factor Sp1 Interact On The Gata3 Promoter

Human T cell leukemia virus type I (HTLV I) is a causative agent of adult T-cell leukemia and the HTLV I associated myelopathy or tropical spastic paraparesis. Although the infection has been reported in every region of the world, moderate-to-high rates of the infection can be found in South America. The majority of seropositive individuals (over 95%) remains asymptomatic. The causes of disease progression are unknown but might involve genetic predisposition, different viral strain and differences in the host immune response. Several lines of evidence suggest that the Tax protein, a 40-kDa transcriptional viral activator, is critical for HTLV-I gene regulation and virus-induced cellular transformation. It seems that several events in HTLV I infected cells are required for the development of the full malignant phenotype. GATA3 is a specific T cell transcription factor , functionally important in the regulation of multiple T-cell specific genes. This transcription factor is an essential and specific regulator of early thymocyte development and is downregulated in HTLVI infection. In order to characterize the relationship between Tax protein and the GATA3 transcription factor, we studied, by Eletrophoretic Mobility Shift Assay (EMSA), the potential interaction of Tax with the GATA3 promoter. The purified Tax protein and anti-Tax antiserum were kindly provided by Dr. Susan J. Marriott. The recombinant human Spl was obtained from Promega (Madison, WI). Our results demonstrated that Tax binds to the GATA3 promoter through the transcription factor Spl. Competition studies showed that the complex formation was specific and supershift analysis demonstrated that Tax was involved in this formation. However, in the absence of Tax, Sp 1 does not bind to the GATA3 promoter. Tax might play a role in early leukemogenesis by expanding the pool of proliferating T cells and thereby creating the condition for subsequent events that lead to T cell malignancy. Therefore, the results here presented may be an important contribution to elucidate the oncogenic potential of Tax protein.9611 PART I

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on "good manufacture practices" (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.442180188Tallman, M.S., Gilliland, D.G., Rowe, J.M., Drug therapy for acute myeloid leukemia (2005) Blood, 106, pp. 1154-1163Arceci, R.J., The potential for antitumor vaccination in acute myelogenous leukemia (1998) J Mol Med (Berl), 76, pp. 80-93Lowdell, M.W., Koh, M.B., Immunotherapy of AML: future directions (2000) J Clin Pathol, 53, pp. 49-54Torelli, G.F., Orsini, E., Guarini, A., Kell, J., Foa, R., Developmental approaches in immunological control of acute myelogenous leukaemia (2001) Best Pract Res Clin Haematol, 14, pp. 189-209Balan, S., Kale, V.P., Limaye, L.S., A large number of mature and functional dendritic cells can be efficiently generated from umbilical cord blood-derived mononuclear cells by a simple twostep culture method Transfusion, 50, pp. 2413-2423Balan, S., Kale, V.P., Limaye, L.S., A simple two-step culture system for the large-scale generation of mature and functional dendritic cells from umbilical cord blood CD34+ cells (2009) Transfusion, 49, pp. 2109-2121Bender, A., Sapp, M., Schuler, G., Steinman, R.M., Bhardwaj, N., Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood (1996) J Immunol Methods, 196, pp. 121-135Romani, N., Gruner, S., Brang, D., Kampgen, E., Lenz, A., Trockenbacher, B., Konwalinka, G., Schuler, G., Proliferating dendritic cell progenitors in human blood (1994) J Exp Med, 180, pp. 83-93Romani, N., Reider, D., Heuer, M., Ebner, S., Kampgen, E., Eibl, B., Niederwieser, D., Schuler, G., Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability (1996) J Immunol Methods, 196, pp. 137-151Tkachenko, N., Wojas, K., Tabarkiewicz, J., Rolinski, J., Generation of dendritic cells from human peripheral blood monocytes--comparison of different culture media (2005) Folia Histochem Cytobiol, 43, pp. 25-30Roddie, H., Klammer, M., Thomas, C., Thomson, R., Atkinson, A., Sproul, A., Waterfall, M., Turner, M., Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia (2006) British journal of haematology, 133, pp. 152-157Charbonnier, A., Gaugler, B., Sainty, D., Lafage-Pochitaloff, M., Olive, D., Human acute myeloblastic leukemia cells differentiate in vitro into mature dendritic cells and induce the differentiation of cytotoxic T cells against autologous leukemias (1999) European journal of immunology, 29, pp. 2567-2578Choudhury, B.A., Liang, J.C., Thomas, E.K., Flores-Romo, L., Xie, Q.S., Agusala, K., Sutaria, S., Claxton, D.F., Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses (1999) Blood, 93, pp. 780-786Kremser, A., Dressig, J., Grabrucker, C., Liepert, A., Kroell, T., Scholl, N., Schmid, C., Schmetzer, H., Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods J Immunother, 33, pp. 185-199van den Ancker, W., van Luijn, M.M., Westers, T.M., Bontkes, H.J., Ruben, J.M., de Gruijl, T.D., Ossenkoppele, G.J., van de Loosdrecht, A.A., Recent advances in antigen-loaded dendritic cell-based strategies for treatment of minimal residual disease in acute myeloid leukemia Immunotherapy, 2, pp. 69-83Kohler, T., Plettig, R., Wetzstein, W., Schmitz, M., Ritter, M., Mohr, B., Schaekel, U., Bornhauser, M., Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells (2000) Stem cells (Dayton, Ohio), 18, pp. 139-147Panoskaltsis, N., Dendritic cells in MDS and AML--cause, effect or solution to the immune pathogenesis of disease? (2005) Leukemia, 19, pp. 354-357Royer, P.J., Tanguy-Royer, S., Ebstein, F., Sapede, C., Simon, T., Barbieux, I., Oger, R., Gregoire, M., Culture medium and protein supplementation in the generation and maturation of dendritic cells (2006) Scand J Immunol, 63, pp. 401-409Mackensen, A., Drager, R., Schlesier, M., Mertelsmann, R., Lindemann, A., Presence of IgE antibodies to bovine serum albumin in a patient developing anaphylaxis after vaccination with human peptide-pulsed dendritic cells (2000) Cancer Immunol Immunother, 49, pp. 152-156Smits, E.L., Anguille, S., Cools, N., Berneman, Z.N., Van Tendeloo, V.F., Dendritic cell-based cancer gene therapy (2009) Hum Gene Ther, 20, pp. 1106-1118Anton, D., Dabadghao, S., Palucka, K., Holm, G., Yi, Q., Generation of dendritic cells from peripheral blood adherent cells in medium with human serum (1998) Scandinavian journal of immunology, 47, pp. 116-121Sorg, R.V., Ozcan, Z., Brefort, T., Fischer, J., Ackermann, R., Muller, M., Wernet, P., Clinical-scale generation of dendritic cells in a closed system (2003) J Immunother, 26, pp. 374-383Peng, J.C., Thomas, R., Nielsen, L.K., Generation and maturation of dendritic cells for clinical application under serum-free conditions (2005) J Immunother, 28, pp. 599-609Vicari, A.P., Caux, C., Trinchieri, G., Tumour escape from immune surveillance through dendritic cell inactivation (2002) Semin Cancer Biol, 12, pp. 33-42Onishi, H., Morisaki, T., Baba, E., Kuga, H., Kuroki, H., Matsumoto, K., Tanaka, M., Katano, M., Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer (2002) Clin Immunol, 105, pp. 286-295Kiertscher, S.M., Luo, J., Dubinett, S.M., Roth, M.D., Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells (2000) J Immunol, 164, pp. 1269-1276Krawczyk, P., Wojas, K., Milanowski, J., Rolinski, J., The influence of different culture microenvironments on the generation of dendritic cells from non-small-cell lung cancer patients (2007) Arch Immunol Ther Exp (Warsz), 55, pp. 405-415Kalinski, P., Vieira, P.L., Schuitemaker, J.H., de Jong, E.C., Kapsenberg, M.L., Prostaglandin E(2) is a selective inducer of interleukin-12 p40 (IL-12p40) production and an inhibitor of bioactive IL-12p70 heterodimer (2001) Blood, 97, pp. 3466-3469Ten Brinke, A., Karsten, M.L., Dieker, M.C., Zwaginga, J.J., van Ham, S.M., The clinical grade maturation cocktail monophosphoryl lipid A plus IFNgamma generates monocyte-derived dendritic cells with the capacity to migrate and induce Th1 polarization (2007) Vaccine, 25, pp. 7145-715

Liver Transplantation In A Patient With Sβo-thalassemia

Background. Patients presenting sickle cell disease may develop different types of hepatic complications. Intrahepatic cholestasis is a potentially fatal complication of the disease, and sometimes the only possible solution is transplantation. Postoperative transfusion management has not yet been well established. In this report, we describe the transfusional program of a patient presenting sickle cell disease and intrahepatic cholestasis who underwent liver transplantation 2 years ago. Methods. Data were obtained from the chart and the blood bank records. Results. The liver transplantation was performed successfully. Despite mild allograft dysfunction 3 months after surgery, secondary to intrahepatic sickling, the patient has been doing well with the transfusional management adopted (sickle-cell hemoglobin <20%). Conclusion. Sickle cell disease should not be a criterion for exclusion from liver transplantation. Regular transfusion with monitoring of sickle-cell hemoglobin is a very important measure to minimize the risk of intrahepatic sickling and possible rejection.746896898Charlotte, F., Bachir, D., Nenert, M., Vascular lesion of the liver in sickle cell disease (1995) Arch Pathol Lab Med, 119, p. 46Diggs, I.W., Sickle cell crisis (1965) Am J Clin Pathol, 44, p. 1Cage, S.J., Masao, O., Myron, J.T., Simmons, J.F., Heiner, J., Tatter, D., Liver involvement in sickle cell disease (1985) Medicine, 15, p. 349Sheehy, T.W., Sickle cell hepatopathy (1977) S Med J, 70, p. 533Sheehy, T.W., Law, D.E., Wade, B.H., Exchange transfusion for sickle cell intrahepatic cholestasis (1980) Arch Intern Med, 140, p. 1364Schubert, T.T., Hepatobiliary system in sickle cell disease (1986) Gastroenterology, 90, p. 2013Shao, S.H., Orringer, E.P., Sickle cell intrahepatic cholestasis: Approach to a difficult problem (1995) Am J Gastroenterol, 90, p. 2048Embre, S., Kitibayashi, K., Schwartz, M.E., Liver transplantation in a patient with acute lever failure due to sickle cell intrahepatic cholestasis (2000) Transplantation, 69, p. 675Lerut, J.P., Claeys, N., Laterre, P.F., Hepatic sickling: An unusual cause of liver allograft dysfunction (1999) Transplantation, 67, p. 6

Molecular Matching Of Red Blood Cells Is Superior To Serological Matching In Sickle Cell Disease Patients

Objective: To evaluate the usefulness of DNA methods to provide a means to precisely genotypically match donor blood units for the antigen-negative type of 35 sickle cell disease patients. Methods: Red blood cell units were investigated for ABO, D, C, c, E, e, K, Fya, Fyb, Jka, Jkb, S, s, Dia and RH variants by performing a molecular array (Human Erythrocyte Antigen BeadChip™, BioArray Solutions), polymerase chain reaction followed by restriction fragment length polymorphism analysis and sequencing of patient samples and donor units that had been serologically matched based on the ABO, Rh and K phenotypes and the presence of antibodies. Results: Matches for 21 of 35 sickle cell disease patients presented discrepancies or mismatches for multiple antigens between the genotype profile and the antigen profile of their serologically-matched blood units. The main discrepancies or mismatches occurred in the RH, FY, JK and MNS systems. Eight Rh alloimmunized patients presented RHD and RHCE variants that had not been serologically identified. According to these results better matches were found for the patients with genotyped units and the patients benefited as shown by better in vivo red blood cell survival. Conclusion: Molecular matching is superior to serological matching in sickle cell disease patients, decreasing the risk of transfusion reactions, especially delayed transfusion reactions to existing alloantibodies and preventing alloimmunization.3513538Giblett, E.R., A critique of the theoretical hazard of inter- vs. intra-racial transfusion (1961) Transfusion, 1, pp. 233-238Davies, S.C., McWilliam, A.C., Hewitt, P.E., Devenish, A., Brozovic, M., Red cell alloimmunization in sickle cell disease (1986) Br J Haematol, 63 (2), pp. 241-245Reisner, E.G., Kostyu, D.D., Philips, G., Walker, C., Dawson, D.V., Alloantibody response in multiply transfused sickle cell patients (1986) Tissue Antigens, 30 (4), pp. 161-166Cox, J.V., Steane, E., Cunningham, G., Frenkel, E.P., Risk of alloimmunization and delayed hemolytic transfusion reactions in patients with sickle cell disease (1988) Arch Intern Med, 148 (11), pp. 2485-2489Rosse, W.F., Gallagher, D., Kinney, T.R., Castro, O., Dosik, H., Moohr, J., Wang, W., Levy, P.S., The cooperative study of sickle cell disease. Transfusion and alloimmunization in sickle cell disease (1990) Blood, 76 (7), pp. 1431-1437Vichinsky, E.P., Earles, A., Johnson, R.A., Hoag, M.S., William, A., Lubin, B., Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood (1990) N Engl J Med, 322 (23), pp. 1617-1621. , Comment in: N Engl J Med. 1990323(20):1420-2N Engl J Med. 1990322(23):1666-1668Orlina, A.R., Sosler, S.D., Koshy, M., Problems of chronic transfusion in sickle cell disease (1991) J Clin Apher, 6 (4), pp. 234-240Sosler, S.D., Jilly, B.J., Saporito, C., Koshy, M., A simple, practical model for reducing alloimmunization in patients with sickle cell disease (1993) Am J Hematol, 43 (2), pp. 103-106Castro, O., Sandler, S.G., Houstoun-Yu, P., Rana, S., Predicting the effect of transfusing only phenotype-matched RBCs to patients with sickle cell disease: Theoretical and practical implications (2002) Transfusion, 42 (6), pp. 684-690Chou, S.T., Westhoff, C.M., The role of molecular immunohematology in sickle cell disease (2011) Transfus Apher Sci, 44 (1), pp. 73-79Vichinsky, E.P., Luban, N.L., Wright, E., Olivieri, N., Driscoll, C., Pegelow, C.H., Adams, R.J., Stroke Prevention Trail in Sickle Cell Anemia. 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(2006) Transfusion, 46 (4), pp. 630-63

Echocardiografic abnormalities in patients with sickle cell/β-thalassemia do not depend on the β-thalassemia phenotype

Objectives and methods: We evaluated possible relationships between echocardiographic findings and clinical and laboratory parameters, in a cohort of Brazilian patients diagnosed with sickle cell/β-thalassemia, to better understand the cardiac involvement in this disease. Results: Left atrial (LA)and left ventricular (LV)dilation were found in 19.5 and 11% of patients, respectively; systolic left ventricular dysfunction was present in a single patient. There were no differences in masses and volumes of cardiac chambers comparing Sβ0 with Sβ+ patients, and no relationship between these parameters and specific complications of the disease. However, parameters of altered ventricular geometry were significantly correlated with serum creatinine, hepatic transaminases and bilirubin levels. Moreover, 3 patients presented stroke; they were significantly older [53 (41–56)× 37.5 (18–70), p = 0.048], had higher values of LV posterior wall diastolic thickness [10 (10–11)× 8 (6–14), p = 0.03], LV mass [226 (194–260)× 147 (69–537), p = 0.039]and LA/aortic ratio [1.545 (1.48–1.61)× 1.26 (0.9–1.48), p = 0.032]. Conclusions: Cardiac involvement in this disease does not appear to depend on the thalassemia phenotype. The presence of signs of myocardial remodeling in this group of patients was related to multi-organ impairment and rendered a higher propensity for stroke in older patients, suggesting the need for greater vigilance and control of associated factors412158163sem informaçãosem informaçã

Il10 Inversely Correlates With The Percentage Of Cd8+ Cells In Mds Patients

The role of the immune system in myelodysplastic syndrome (MDS) progression has been widely accepted, although mechanisms underlying this immune dysfunction are not clear. CD4+ and CD8+ lymphocyte profiles in the peripheral blood of MDS patients were evaluated and correlated with clinical characteristics, the expression of FOXP3 and the anti-inflammatory cytokines IL10, TGFβ1 and CTLA4. IL10 expression inversely correlated with the percentage of CD8+ cells and was higher in high-risk MDS. 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