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‣ Heart Transplantation in Arrhythmogenic Right Ventricular Dysplasia: Case Reports

FIORELLI, A. I.; COELHO, G. H. B.; OLIVEIRA JR., J. L.; NASCIMENTO, C. N. G.; BOAS, L. B. Vilas; NAPOLITANO, C. F. C.; BACAL, F.; BOCHI, E. A.; STOLF, N. A. G.
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
Português
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Objective. Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disease of familiar, origin where the myocardium is replaced by fibrofatty tissue predominantly in the right ventricle. Herein we have presented the clinical courses of 4 patients with ARVD who underwent orthotopic heart transplantation. Patients and Methods. Among 358 adult patients undergoing heart transplantation, 4 (1.1%) displayed ARVD. The main indication for transplantation was the progression to heart failure associated with arrhythmias. All 4 patients displayed rapid, severe courses leading to heart failure with left ventricular involvement and uncontrolled arrhythmias. Results. In all cases the transplantation was performed using a bicaval technique with prophylactic tricuspid valve annuloplasty. One patient developed hyperacute rejection and infection, leading to death on the 7th day after surgery. The other 3 cases showed a good evolution with clinical remission of the symptoms. Pathological study of the explanted hearts confirmed the presence of the disease. Conclusions. ARVD is a serious cardiomyopathy that can develop malignant arrhythmias, severe ventricular dysfunction with right ventricular predominance, and sudden cardiac death. Orthotopic heart transplantation must always be considered in advanced cases of ARVD with malignant arrhythmias or refractory congestive heart failure with or without uncontrolled arrhythmias...

‣ Experimental multivisceral xenotransplantation

GALVAO, Flavio Henrique; POMPEU, Eduardo; MELLO, Evandro Sobroza de; COSTA, Anderson da Costa Lino; MORY, Eduardo; SANTOS, Rafael Miyashiro dos; SANTOS, Vinicius Rocha; MACHADO, Marcel Cesar; BACCHELLA, Telesforo
Fonte: WILEY-BLACKWELL PUBLISHING, INC Publicador: WILEY-BLACKWELL PUBLISHING, INC
Tipo: Artigo de Revista Científica
Português
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Background: Organ shortage impairs the proposition of multivisceral transplantation to treat multiple organ failure. Interspecies (xeno) transplantation is a valid solution for organ shortage; however, suitable models of this advance are lacking. We describe an effective model of multivisceral xenotransplantation to study hyperacute rejection. Methods: Under general anesthesia, we in block recovered the distal esophagus, stomach, small bowel, colon, liver, pancreas, spleen, and kidneys from donors and implanted heterotopically in the lower abdomen of recipients. Animals were divided into four groups: I-canine donor, swine recipient (n = 6); II - swine donor, canine recipient (n = 5); III-canine donor, canine recipient (n = 4); and IV-swine donor, swine recipient (n = 5). Groups I and 11 comprised experimental (xenotransplantation) and III and IV control groups (allotransplantation). During the experiment, we appraised recipient evolution and graft modification by sequential biopsy up to 3 h. At this time, we killed animals for autopsy (experimental end point). Results: We accomplished all experiments successfully. Every grafts attained customary appearance and convenient urine output immediately after unclamp. Around 15 min after reperfusion...

‣ Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

AYUB-FERREIRA, S. M.; AVILA, M. S.; FEITOSA, F. S.; SOUZA, G. E. C.; MANGINI, S.; MARCONDES-BRAGA, F. G.; ISSA, V. S.; BACAL, F.; CHIZZOLA, P. R.; CRUZ, F. D. D.; BOCCHI, E. A.
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
Português
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Background. Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. Methods. The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance <50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL...

‣ Protective Effect of N-acetylcysteine on Early Outcomes of Deceased Renal Transplantation

DANILOVIC, A.; LUCON, A. M.; Srougi, Miguel; SHIMIZU, M. H. M.; IANHEZ, L. E.; NAHAS, W. C.; SEGURO, A. C.
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
Português
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We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.; FAPESP[06/52046-0]

‣ Prospective analysis between the therapy of immunosuppressive medication and allogeneic microchimerism after liver transplantation

ARAUJO, M. B.; LEONARDI, L. S.; LEONARDI, M. I.; BOIN, I. F. S. F.; MAGNA, L. A.; DONADI, E. A.; KRAEMER, M. H. S.
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
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After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in pheripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was colleted from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p=0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donor-derived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction. (C) 2008 Elsevier B.V. All rights reserved.; FAPESP-Sao Paulo State Research Foundation; FAEP (Teaching and Research Support Found)-UNICAMP; Universidade de São Paulo - Immunology Molecular Laboratory of the Clinical Hospital of the Medical Faculty of RibeirAo Preto (FMRP-USP-SP)

‣ Transplantation for Autoimmune Diseases in North and South America: A Report of the Center for International Blood and Marrow Transplant Research

Pasquini, Marcelo C.; Voltarelli, Julio; Atkins, Harold L.; Hamerschlak, Nelson; Zhong, Xiaobo; Ahn, Kwang Woo; Sullivan, Keith M.; Carrum, George; Andrey, Jeffrey; Bredeson, Christopher N.; Cairo, Mitchell; Gale, Robert Peter; Hahn, Theresa; Storek, Jan;
Fonte: ELSEVIER SCIENCE INC; NEW YORK Publicador: ELSEVIER SCIENCE INC; NEW YORK
Tipo: Artigo de Revista Científica
Português
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Hematopoietic cell transplantation (HCT) is an emerging therapy for patients with severe autoimmune diseases (AID). We report data on 368 patients with AID who underwent HCT in 64 North and South American transplantation centers reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2009. Most of the HCTs involved autologous grafts (n = 339); allogeneic HCT (n = 29) was done mostly in children. The most common indications for HCT were multiple sclerosis, systemic sclerosis, and systemic lupus erythematosus. The median age at transplantation was 38 years for autologous HCT and 25 years for allogeneic HCT. The corresponding times from diagnosis to HCT were 35 months and 24 months. Three-year overall survival after autologous HCT was 86% (95% confidence interval [CI], 81%-91%). Median follow-up of survivors was 31 months (range, 1-144 months). The most common causes of death were AID progression, infections, and organ failure. On multivariate analysis, the risk of death was higher in patients at centers that performed fewer than 5 autologous HCTs (relative risk, 3.5; 95% CI, 1.1-11.1; P = .03) and those that performed 5 to 15 autologous HCTs for AID during the study period (relative risk, 4.2; 95% CI...

‣ Avaliação da reconstituição imunológica e da resposta anti-citomegalovirus nos receptores de transplante de medula óssea; Anti-cytomegalovirus immunity reconstitution following autologous and allogeneic stem cell and bone marrow transplantation as assessed by CD8+ T cell phenotyping and functio

Ferrari, Valeria
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 23/02/2005 Português
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O citomegalovírus (CMV) é uma séria ameaça aos receptores de transplante de medula óssea. A reativação está associada com uma imunidade mediada por células TCD8+ defeituosa. Nosso objetivo foi correlacionar as diferentes subpopulações de células TCD8+ com a reconstituição imunológica dos pacientes, especificamente a imunidade anti-CMV, analisando as subpopulações de células T infundidas nas diferentes modalidades de transplante de medula óssea. Receptores de transplante alogênico de células tronco mobilizadas para o sangue periférico (n=16) ou coletadas diretamente da medula óssea (n=28) e receptores de transplante autólogo de células tronco mobilizadas para o sangue periférico (n=22) foram avaliados. Verificamos que as transferências de células mobilizadas para o sangue periférico dos doadores, tanto nos transplantes alogênicos como autólogos, são proporcionalmente enriquecidas por subpopulações de células memória efetora e efetora, comparadas às transferências de células procedentes diretamente da medula óssea. Este enriquecimento por subpopulações de células TCD8+ mais diferenciadas foi também correlacionado com maior número de células contendo altos níveis de granzima B, considerado um marcador para linfócitos citotóxicos...

‣ Caracterização da resposta inflamatória no enxerto singênico e alogênico em modelo experimental de transplante de pele.; Characterization of the inflammatory response in the syngeneic and allogeneic graft in an experimental model of skin transplantation.

Takiishi, Tatiana
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 24/07/2008 Português
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A inflamação é um evento intrínseco ao transplante que é desencadeado após o dano causado pela cirurgia. No presente trabalho realizou-se a caracterização fenotípica e funcional das células inflamatórias presentes no enxerto, após o transplante alogênico ou singênico de pele em camundongos. Os resultados obtidos mostraram diferenças significativas na produção de citocinas pró e anti-inflamatórias entre o transplante alogênico e singênico, diferenças já detectáveis nas primeiras 24 horas pós-transplante. Mostrou-se que existe produção aumentada de IL-10 no transplante singênico em relação ao transplante alogênico indicando que a produção de IL-10 no enxerto possui um importante papel para o aceite de transplantes de pele. Além disso, na ausência de IL-10, a rejeição de enxertos alogênicos apresentou-se acelerada e surpreendentemente uma grande parcela dos enxertos singênicos não foi aceita e apresentava aspecto de fibrose com grande deposição de colágeno. O conjunto dos dados indica que a IL-10 possui um importante papel regulatório na inflamação local do enxerto.; Inflammation is an intrinsic event of transplantation that occurs due to to damage caused by surgery. In this study, phenotypic and functional characterization of inflammatory cells present in the graft was performed...

‣ Leptina: um modulador central das respostas imunes.; Leptin: a central modulator of imune responses.

Vieira, Pedro Manoel Mendes de Moraes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 07/10/2011 Português
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A leptina é um mediador tanto de respostas neuroendócrinas como imunes, e tem sido associada a diversas autoimunidades. O nosso objetivo foi estudar a importância da leptina na modulação da resposta imunológica no transplante experimental, com ênfase em seu papel na plasticidade de linfócitos T e de células dendríticas (DC). Observamos que os animais deficientes em leptina têm uma sobrevida aumentada do enxerto de pele e uma menor frequência de células Th1 e maior T reguladoras (Treg), Th2 e Th17. Ademais, células T CD4+ naive diferenciam-se mais eficientemente em células Treg e Th17 tanto com DC como sem DC, na ausência de leptina. Nossos dados indicam que BMDC, imaturas e maduras, é comprometida na ausência de leptina, induzindo menor proliferação de linfócitos CD4+ e maior geração/expansão de células Treg, Th17 e Th2. Assim, a ausência de leptina resultou num predomínio de células Treg um padrão Th2 que, em conjunto com o perfil tolerogênico das DC, poderiam ser um dos mecanismos responsáveis pelo aumento da sobrevida do enxerto alogenêico de pele.; Leptin is a mediator of both neuroendocrine and immune responses, and has been associated with several autoimmune diseases. Our objective was to study the importance of leptin in modulating the immune response in experimental transplantation...

‣ Análise da sobrevida do paciente e do enxerto de diabéticos submetidos a diferentes modalidades de transplante; Analysis of patient and graft survival of diabetic patients undergoing different modalities of transplantation

Mesquita, Pablo Girardelli Mendonça
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 11/12/2013 Português
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O diabetes mellitus (DM) é a principal causa de doença renal crônica (DRC) em vários países do mundo. Para pacientes diabéticos com DRC estágio 5 e indicação da terapia renal substitutiva, o transplante (Tx) renal representa uma modalidade terapêutica com técnica bem estabelecida e com excelentes resultados. O transplante simultâneo de rim-pâncreas (TSRP), uma alternativa mais recente praticada em um número mais restrito de centros, apresenta resultados positivos adicionais no controle metabólico, na qualidade de vida e nas complicações crônicas do diabetes. Entretanto, está associado a um risco maior de complicações pós-operatórias e maior número de internações. Tanto o transplante renal quanto o TSRP estão associados a melhor sobrevida do paciente em relação à diálise. A escolha da melhor modalidade de transplante para o paciente diabético com DRC ainda não está clara. O objetivo deste estudo foi analisar os resultados de diferentes modalidades de transplante em pacientes diabéticos com DRC estágio 5, realizados em 3 Centros Brasileiros de Transplante. Assim, analisar a sobrevida do paciente e do enxerto renal após 1, 5 e 8 anos em pacientes DM tipo 1 submetidos a TSRP comparados com transplante renal isolado com doador vivo (DM1-DV) ou transplante de renal isolado com doador falecido (DM1-DF) (Estudo de 3 modalidades de Tx em DM tipo1). Além disso...

‣ Microsurgical techniques for experimental kidney transplantation and general guidelines to establish studies about transplantation immunology

Martins,Paulo Ney Aguiar; Filatenkov,Alexander
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2003 Português
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Experimental models of organ transplantation played a crucial role to establish the principles of transplantation immunology. The renal transplantation in rodents became the most used model to study the mechanisms of allograft rejection. To perform it, it is necessary to master the microsurgery techniques and the research group should cooperate with other specialists in the field. In this article we review the surgical techniques employed in rats, and we draw guidelines to establish studies about transplantation immunology.

‣ Advances in haploidentical stem cell transplantation

Bayraktar,Ulas Darda; Lima,Marcos de; Ciurea,Stefan Octavian
Fonte: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Publicador: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2011 Português
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Hematopoietic stem cell transplantation from haploidentical donors is an attractive method of transplantation due to the immediate donor availability, ease of stem cell procurement and the possibility to collect additional donor cells for cellular therapy, if needed. Historically, maintaining T-cells in the graft has been associated with very high rates of graft-versus-host disease, while T-cell depleted haploidentical transplantation has been limited by a higher incidence of graft rejection and delayed immune reconstitution post-transplant. Recent approaches attempt to maintain the T-cells in the graft while effectively preventing the development of graft-versus-host disease post-transplant. Selective depletion of alloreactive T-cells post-transplant using high-dose post-transplant cyclophosphamide is under investigation as a promising alternative in haploidentical transplantation. While engraftment has improved and graft-versus-host disease is controlled with this approach, future directions should focus on optimizing conditioning regimens and the prevention of disease relapse post-transplant.

‣ Intestinal and multivisceral transplantation

Meira Filho,Sérgio Paiva; Guardia,Bianca Della; Evangelista,Andréia Silva; Matielo,Celso Eduardo Lourenço; Neves,Douglas Bastos; Pandullo,Fernando Luis; Felga,Guilherme Eduardo Gonçalves; Alves,Jefferson André da Silva; Curvelo,Lilian Amorim; Diaz,Lu
Fonte: Instituto Israelita de Ensino e Pesquisa Albert Einstein Publicador: Instituto Israelita de Ensino e Pesquisa Albert Einstein
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2015 Português
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Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently...

‣ Vascularized thymic lobe transplantation in miniature swine: Thymopoiesis and tolerance induction across fully MHC-mismatched barriers

Kamano, Chisako; Vagefi, Parsia A.; Kumagai, Naoki; Yamamoto, Shin; Barth, Rolf N.; LaMattina, John C.; Moran, Shannon G.; Sachs, David H.; Yamada, Kazuhiko
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
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As the major site of self-nonself discrimination in the immune system, the thymus, if successfully transplanted, could potentially carry with it the induction of central tolerance to any other organ or tissue from the same donor. We have recently developed a technique for transplantation of an intact, vascularized thymic lobe (VTL) in miniature swine. In the present study, we have examined the ability of such VTL allografts to support thymopoiesis and induce transplantation tolerance across fully MHC-mismatched barriers. Six miniature swine recipients received fully MHC-mismatched VTL grafts with a 12-day course of tacrolimus. Three of these recipients were thymectomized before transplantation and accepted their VTL allografts long-term, with evidence of normal thymopoiesis. In contrast, three euthymic recipients rejected their VTL allografts. Donor renal allografts, matched to the donor VTL grafts, were transplanted without immunosuppression into two of the three thymectomized recipients, and one of the three euthymic recipients. These renal allografts were accepted by thymectomized recipients, but rejected by the euthymic recipient in an accelerated fashion. This study thus demonstrates that successful transplantation of a vascularized thymus across a fully MHC-mismatched barrier induces tolerance in this preclinical...

‣ Antibody Response to Cryptococcus neoformans Capsular Polysaccharide Glucuronoxylomannan in Patients after Solid-Organ Transplantation

Jalali, Ziba; Ng, Lucky; Singh, Nina; Pirofski, Liise-anne
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2006 Português
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Cryptococcosis is an important complication of solid-organ transplantation, but the risk factors for disease are poorly understood. The goal of this study was to investigate whether specific or nonspecific serum immunoglobulin levels determined in samples obtained before and after solid-organ transplantation differed in patients who did or did not develop cryptococcosis after transplantation. We analyzed pretransplantation sera from 25 subjects, 15 who subsequently developed cryptococcosis and 10 who did not, and posttransplantation sera from 24 subjects, 13 who developed cryptococcosis and 11 who did not. All subjects received a tacrolimus-based immunosuppressive regimen. Total immunoglobulin levels were measured by immunodiffusion, and Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM)-specific serum antibody levels were determined by enzyme-linked immunosorbent assays. The results showed that solid-organ transplantation had a significant effect on total immunoglobulin and GXM-reactive antibody levels. GXM-reactive antibody levels differed in subjects who did and did not develop cryptococcosis. In pretransplant serum samples, the levels of GXM-reactive immunoglobulin M (IgM) were significantly lower in subjects who developed cryptococcosis after transplantation than in those who did not. For posttransplant serum samples...

‣ Antagonistic effect of toll-like receptor signaling and bacterial infections on transplantation tolerance*

Alegre, Maria-Luisa; Chen, Luqiu; Wang, Tongmin; Ahmed, Emily; Wang, Chyung-Ru; Chong, Anita
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/05/2009 Português
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The induction of donor-specific tolerance remains a major goal in the field of transplantation immunology. Therapies that target costimulatory molecules can induce tolerance to heart and pancreatic islet allografts in mouse models, but fail to do so following transplantation of skin or intestinal allografts. We have proposed that organs colonized by commensal bacteria such as skin, lung and intestine may be resistant to such therapies as a result of bacterial translocation at the time of transplantation, which may promote antigen-presenting cell (APC) maturation and the production of pro-inflammatory cytokines, consequently enhancing responses of alloreactive T cells. Our results indicate that the inability to sense signaling by most toll-like receptors (TLRs), as well as by interleukin (IL)-1R and IL-18R, as a result of genetic ablation of myeloid differentiation factor 88 (MyD88) promotes the acceptance of skin allografts. Conversely, TLR signals and infections by a model bacterium, Listeria monocytogenes (LM), at the time of transplantation can prevent the induction of transplantation tolerance. The effects of the TLR9 agonist CpG are MyD88-dependent, while the pro-rejection capacity of LM depends on the intracellular sensing of LM and the production of type I interferon (IFN). Therefore...

‣ The Unfinished Legacy of Liver Transplantation: Emphasis on Immunology

Starzl, Thomas E.; Lakkis, Fadi G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/2006 Português
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Liver transplantation radically changed the philosophy of hepatology practice, enriched multiple areas of basic science, and had pervasive ripple effects in law, public policy, ethics, and theology. Why organ engraftment was feasible remained enigmatic, however, until the discovery in 1992 of donor leukocyte microchimerism in long-surviving liver, and other kinds of organ recipients. Following this discovery, the leukocyte chimerism-associated mechanisms were elucidated that directly linked organ and bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. We describe here how the initially controversial paradigm shift mandated revisions of cherished dogmas. With the fresh insight, the reasons for numerous inexplicable phenomena of transplantation either became obvious or have become susceptible to discriminate experimental testing. The therapeutic implications of the “new immunology” in hepatology and in other medical disciplines, have only begun to be explored. Apart from immunology, physiologic investigations of liver transplantation have resulted in the discovery of growth factors (beginning with insulin) that are involved in the regulation of liver size...

‣ THEMES OF LIVER TRANSPLANTATION

Starzl, Thomas E.; Fung, John J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/2010 Português
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Liver transplantation was the product of 5 interlocking themes. These began in 1958-59 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g. familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and ALG. With this regimen, the world’s longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979) which was replaced in turn by tacrolimus (1989). However...

‣ First case of simultaneous heart plus kidney transplantation in Chile: Case report

Cotera, A.; Alvarez, F.; Castillo, R.; Bermúdez, C.; Llancaqueo, Marcelo; Núñez, N.; González, M.; Zamorano, J.; Sepúlveda Morales, Luis Alberto
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo de revista
Português
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Publicación ISI; Advanced renal disease is a formal contraindication to heart transplantation, and heart failure may make a patient ineligible for kidney transplantation. The International Society of Heart and Lung Transplantation has reported 336 simultaneous heart and kidney transplantations with a 70% rate of 5 year survival. Herein we have presented the first case of simultaneous heart plus kidney transplantation in Chile. The patient is a 62-year-old man with diabetes mellitus and arterial hypertension who in 1997 had a myocardial infarction with cardiogenic shock and acute renal failure. He underwent a coronary bypass but developed progressive heart failure, with an ejection fraction less than 20% and moderate mitral regurgitation. He required chronic hemodialysis and survived a cardiac arrest, receiving an implantable cardioverter defibrillator. Transplantation was performed in 2004 in 2 phases: initially a heart, followed by a kidney transplantation. Immunosuppression included Daclizumab, cyclosporine, mycophenolate mofetil (MMF) and steroids. He developed acute renal failure but did not receive dialysis. He left the hospital at 25 days posttransplantation. Two years following double transplantation, he has not shown acute rejection episodes of either the cardiac or the kidney graft. Both cardiac and renal functions are normal. In conclusion...

‣ Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

O'Valle, Francisco; Moral, Raimundo M.G. del; Ben??tez, Mar??a del Carmen; Mart??n Oliva, David; G??mez-Morales, Mercedes; Aguilar, David; Aneiros-Fern??ndez, Jos??; Hern??ndez-Cort??s, Pedro; Osuna Ortega, Antonio; Moreso, Francesc; Ser??n, Daniel; Olive
Fonte: Public Library of Science (PLOS) Publicador: Public Library of Science (PLOS)
Tipo: Artigo de Revista Científica
Português
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Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). [Materials and Methods] Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. [Results] PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary...