ALEXANDRE CHAGAS DE SANTANA
Projetos de Pesquisa
Unidades Organizacionais
DIR CLINIC, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Effects of Human Amniotic Fluid Stem Cells in a Model of Aorta Allograft Vasculopathy(2012) SANTANA, A. C.; DELLE, H.; CAVAGLIERI, R. C.; LOPES, M. A. B.; FRANCISCO, R. P. V.; ZUGAIB, M.; BYDLOWSKI, S. P.; NORONHA, I. L.Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune-in flammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid derived stem cells (hAFSC), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells display immunomodulatory properties. hAFSC express mesenchymal and embryonic markers, show high proliferation rates, but do not induce tumor formation and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into 3 groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n=8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n=8); and ALLO+hAFSC, ALLO rats treated with hAFSC (106 cells) (n=8). Histological analysis and immunohistochemistry were performed 30 days post transplantation. ALLO developed a robust aortic neointimal formation, accompanied by a high number of ED1+ and CD43+ cells, and enhanced expression of α-SMA in theneointima. Treatment with hAFSC diminished neointimal thickness and induced a significant decrease of ED1+, CD43+ cells and α-SMA expression in the neointima. Comparative analyses in the differents groups PARAMETERS SYNG ALLO ALLO+hAFSC Neointima thickness (μm) 0±0 208.7±25.4* 180.7±23.7* ED-1+ (cells/mm2) 0±0 4.845±841* 1.100±276*, #CD43+ (cells/mm2) 0±0 4.064±563* 1.080±309*,#α-SMA (%) 0±0 25±6* 8±3*, #*p<0.05 vs. SYNG; #P<0.05 vs. ALLO These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.conferenceObject Paclitaxel Delivered With Nanoparticles Inhibits Neointimal Formation and Local Inflammation in Experimental Chronic Allograft Vasculopathy(2014) PEPINELI, R.; SANTANA, A.; TIEME, A.; DEUS, D.; MARANHAO, R.; NORONHA, I.- Immunomodulatory effect of thalidomide in the kidney of donor brain death experimental model.(2019) SILVA, Filipe; SANATANA, Alexandre C.; PEPINELI, Rafael; FELICIANO, Regiane S.; SALA, Ana C. G.; SCHUST, Amanda S.; NERI, Luis M.; FIGUEIREDO, Eberval G.; FERNANDES, Paulo M. P.; NEPOMUCENO, Natalia A.; RUIZ, Liliane M.; DELLE, Humberto
- Immunomodulatory response in an experimental model of brain death(2023) SANTANA, Alexandre Chagas; ANDRAUS, Wellington; OBERMAN, Dan Zimelewicz; RABELO, Nicollas Nunes; SILVA, Filipe Miranda Oliveira; DELLE, Humberto; PEPINELI, Rafael; MORAES, Edvaldo Leal de; SCAVONE, Cristoforo; LIMA, Larissa de Sa; DEGASPARI, Sabrina; BRASIL, Sergio; SOLLA, Davi Jorge Fontoura; RUIZ, Liliane Moreira; OLIVEIRA-BRAGA, Karina Andrighetti de; NEPOMUCENO, Natalia Aparecida; PEGO-FERNANDES, Paulo Manuel; TULLIUS, Stefan Gunther; FIGUEIREDO, Eberval GadelhaLiver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group. We studied two groups: Control and BD (rats subjected to BD by increasing intracranial pressure). After the induction of BD, there was an intense rise in blood pressure followed by a fall. There were no significant differences observed between the groups. Blood tissue and hepatic tissue analyzes showed an increase in plasma concentrations of liver enzymes (AST, ALT, LDH and ALP), in addition to pro-inflammatory cytokines and macrophages in liver tissue in animals submitted to BD. The current study found that BD is a multifaceted process that elicits both a systemic immune response and a local inflammatory response in liver tissue. Our findings strongly suggested that the immunogenicity of plasma and liver increased with time following BD.
- Use of paclitaxel carried in lipid nanoparticles to treat aortic allograft transplantation in rats(2021) PEPINELI, Rafael; SANTANA, Alexandre C.; SILVA, Filipe M. O.; TAVONI, Thauany M.; STOLF, Noedir A. G.; NORONHA, Irene L.; MARANHAO, Raul C.Objectives The aim of this study was to test whether lipid core nanoparticles loaded with paclitaxel (LDE-PTX) protect rat aortic allograft from immunological damage. Methods Fisher and Lewis rats were used differing in minor histocompatibility loci. Sixteen Lewis rats were allocated to four-animal groups: SYNG (syngeneic), Lewis rats receiving aorta grafts from Lewis rats; ALLO (allogeneic), Lewis rats receiving aortas from Fisher rats; ALLO+LDE (allogeneic transplant treated with LDE), Lewis rats receiving aortas from Fisher rats, treated with LDE (weekly injection for 3 weeks); ALLO+LDE-PTX (allogeneic transplant treated with LDE-PTX), Lewis rats receiving aortas from Fisher rats treated with LDE-PTX (4 mg/kg weekly for 3 weeks). Treatments began on transplantation day. Results Thirty days post-transplantation, SYNG showed intact aortas. ALLO and ALLO+LDE presented intense neointimal formation. In ALLO+LDE-PTX, treatment inhibited neointimal formation; narrowing of aortic lumen was prevented in ALLO and ALLO+LDE. LDE-PTX strongly inhibited proliferation and intimal invasion by smooth muscle cells, diminished 4-fold presence of apoptotic/dead cells in the intima, reduced the invasion of aorta by macrophages and T-cells and gene expression of pro-inflammatory tumour necrosis factor-alpha (TNF alpha), interferon gamma (IFN gamma) and interleukin-1 beta (IL-1 beta). Conclusions LDE-PTX was effective in preventing the vasculopathy associated with rejection and may offer a potent therapeutic tool for post-transplantation.
- Immunomodulatory effects of thalidomide in an experimental brain death liver donor model(2021) SANTANA, Alexandre Chagas; ANDRAUS, Wellington; SILVA, Filipe Miranda Oliveira; DELLE, Humberto; PEPINELI, Rafael; MORAES, Edvaldo Leal de; SCAVONE, Cristoforo; LIMA, Larissa de Sa; DEGASPARI, Sabrina; BRASIL, Sergio; SOLLA, Davi Jorge Fontoura; RUIZ, Liliane Moreira; OLIVEIRA-BRAGA, Karina Andrighetti de; NEPOMUCENO, Natalia Aparecida; PEGO-FERNANDES, Paulo Manuel; TULLIUS, Stefan Gunther; FIGUEIREDO, Eberval GadelhaBrain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-alpha, IL1-beta, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-kappa B, and macrophage infiltration. NF-kappa B was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-alpha, IL-1-beta, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-kappa B activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-kappa B activation.
conferenceObject Human Amniotic Fluid Stem Cells Reduce Neointimal Formation and Inflammation in a Model of Aortic Allograft Vasculopathy(2012) SANTANA, A. C.; CAVAGLIERI, R. C.; DELLE, H.; LOPES, M. A. B.; V, R. P. Francisco; ZUGAIB, M.; BYDLOWSKI, S. P.; NORONHA, I. L.conferenceObject Immunomodulatory Properties of Thalidomide in the Chronic Allograft Vasculopathy Model: Inhibition of Pro-Inflammatory Cytokines and NF kappa-B Activation.(2014) SANTANA, A.; SCAVONE, C.; LIMA, L.; NORONHA, I.- Family Interview to Enable Donation of Organs for Transplantation: Evidence-based Practice(2018) MORAES, E. L. de; SANTO, M. J. dos; SILVA, L. B. de Barros e; PILAN, L. A. S. de Lima; LIMA, E. A. A. de; SANTANA, A. G. de; MARTINS, M. S.Background. In this study we propose a theoretical and practical basis for the best practices for interviewing relatives of brain-dead eligible organ donors. Methods. This investigation was a reflective study of the methodologic factors of the family interview that affect their decision regarding the donation of a deceased patient's organs for transplantation. The articles that formed the empirical basis of the trial were obtained from PubMed, which is a free-access tool of the MEDLINE database of the United States National Library of Medicine. Published articles that allowed us to reflect on evidence-based family interview practice were selected. Results. Thirty-six scientific articles were used to guide our assessment the family interview, providing evidence for its adequate execution in view of the following prerequisites: When should the family interview be performed? Where should it be done? How many and which people should participate in the interview? Who should perform it? How should it be done? Conclusion. Scientific studies offer evidence to donation and transplantation specialists that can help them in their daily work regarding their interactions with relatives in the process of decisionmaking and family consent.
conferenceObject Paclitaxel Delivered With Nanoparticles Inhibits Neointimal Formation and Local Inflammation in Experimental Chronic Allograft Vasculopathy.(2014) PEPINELI, R.; SANTANA, A.; TIEME, A.; DEUS, D.; MARANHAO, R.; NORONHA, I.