ELAINE RUFO TAVARES
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conferenceObject Regression of atherosclerotic plaques of cholesterol-fed rabbits by combined chemotherapy of paclitaxel and methotrexate carried in lipid core nanoparticles(2017) GOMES, F. T. Torres; MARANHAO, R. C.; TAVARES, E. R.; CARVALHO, P. O.; MATTOS, F. R.; MACHADO, T.; HIGUCHI, M. L.; HATAB, S. A.; FILHO, R. Kalil; SERRANO JUNIOR, C. V.- Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions(2011) TAVARES, Elaine R.; FREITAS, Fatima R.; DIAMENT, Jayme; MARANHAO, Raul C.Objectives: Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated. Methods: Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections. Results: LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1 beta and tumor necrosis factor-alpha), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase II alpha and tubulin). Conclusion: The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.
- Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE)(2023) ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; GUIDO, Maria Carolina; CARVALHO, Priscila Oliveira; TAVONI, Thauany Martins; LOPES, Natalia Menezes; SILVA, Bruna Miranda de Oliveira; JENSEN, Leonardo; STOLF, Noedir Antonio Groppo; MARANHA, Raul CavalcanteAtherosclerosis is a cell-proliferative, chronic inflammatory process. The aim was to investigate whether lipid core nanoparticles (LDE) carrying the anti-cancer agent daunorubicin could have anti-atherosclerotic effects. LDE is taken-up by cellular lipoprotein receptors and is capable of concentrating incorporated drugs in inflammed tissues. New Zealand male rabbits were fed 1% cholesterol diet for 8 weeks. Then, animals were treated with LDE-daunorubicin (6 mg/kg/week, IV, n = 9) or with LDE only (n = 7). Atherosclerotic lesions in LDE-daunorubicin group were 50% smaller than in LDE group. In LDE-daunorubicin, protein expressions of the pro-inflammatory markers CD68, TNF-alpha IL-6 and gene expression MCP-1 were lower than in LDE. Gene expression of IL-1 beta, IL-18 and IL-10 were similar. Protein expressions of VEGF and of pro-apoptotic caspase 3, caspase 9 and BAX, and both protein and gene expressions of VCAM-1 were all lower in LDE-daunorubicin. Gene expression of MMP-12 and protein expression of MMP-2 were lower in LDE-daunorubicin, but MMP-9 was not different. Daunorubicin is known as cardiotoxic, but at echocardiography, LDE-daunorubicin had no differences in arch aorta diameters, systolic and diastolic function and in cardiac hypertrophy compared to LDE group. LDEdaunorubicin was capable of reducing atherosclerotic lesions by different mechanisms without observable toxicities.
conferenceObject Anti-cellular Proliferation Therapy Reduces Atherosclerotic Plaques and Vascular Inflammation in Experimental Hypercholesterolemia(2016) GOMES, Fernando L.; MARANHAO, Raul C.; TAVARES, Elaine R.; OLIVEIRA, Priscila C.; MACHADO, Thiago V.; SOEIRO, Alexandre M.; HIGUCHI, Maria de Lourdes; KALIL-FILHO, Roberto; SERRANO, Carlos V.- LIPID CORE NANOPARTICLES AS VEHICLE FOR DOCETAXEL REDUCES ATHEROSCLEROTIC LESION, INFLAMMATION, CELL DEATH AND PROLIFERATION IN AN ATHEROSCLEROSIS RABBIT MODEL(2018) MENEGHINI, Bianca C.; TAVARES, Elaine R.; GUIDO, Maria C.; TAVONI, Tauany M.; KALLIL FILHO, Roberto; MARANHAO, Raul C.
- Effect of paclitaxel and methotrexate associated with cholesterol-rich nanoemulsions on ischemiareperfusion injury after unilateral lung transplantation in rats(2023) BATTOCHIO, Angela; TAVARES, Elaine; CORREIA, Aristides; ALMEIDA, Francine; CARVALHO, Priscila; GUIDO, Maria; PEGO-FERNANDES, Paulo; MARANHAO, Raul; PAZETTI, Rogerio
- An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: A study in a rabbit graft model(2011) LOURENCO-FILHO, Domingos D.; MARANHAO, Raul C.; MENDEZ-CONTRERAS, Carlos A.; TAVARES, Elaine R.; FREITAS, Fatima R.; STOLF, Noedir A.Objective: In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure. Methods: Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg . kg(-1) . d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake. Results: Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment. Conclusions: LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies. (J Thorac Cardiovasc Surg 2011;141:1522-8)
- Treatment With Methotrexate Associated With Lipid Core Nanoparticles Prevents Aortic Dilation in a Murine Model of Marfan Syndrome(2022) GUIDO, Maria Carolina; LOPES, Natalia de Menezes; ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; JENSEN, Leonardo; CARVALHO, Priscila de Oliveira; TAVONI, Thauany Martins; DIAS, Ricardo Ribeiro; PEREIRA, Lygia da Veiga; LAURINDO, Francisco Rafael Martins; MARANHAO, Raul CavalcanteIn Marfan syndrome (MFS), dilation, dissection, and rupture of the aorta occur. Inflammation can be involved in the pathogenicity of aortic defects and can thus be a therapeutic target for MFS. Previously, we showed that the formulation of methotrexate (MTX) associated with lipid nanoparticles (LDE) has potent anti-inflammatory effects without toxicity. To investigate whether LDEMTX treatment can prevent the development of aortic lesions in the MFS murine model. Mg Delta loxPneo MFS (n = 40) and wild-type (WT, n = 60) mice were allocated to 6 groups weekly injected with IP solutions of: (1) only LDE; (2) commercial MTX; (3) LDEMTX (dose = 1mg/kg) between 3rd and 6th months of life. After 12 weeks of treatments, animals were examined by echocardiography and euthanatized for morphometric and molecular studies. MFS mice treated with LDEMTX showed narrower lumens in the aortic arch, as well as in the ascending and descending aorta. LDEMTX reduced fibrosis and the number of dissections in MFS but not the number of elastic fiber disruptions. In MFS mice, LDEMTX treatment lowered protein expression of pro-inflammatory factors macrophages (CD68), T-lymphocytes (CD3), tumor necrosis factor-alpha (TNF-alpha), apoptotic factor cleaved-caspase 3, and type 1 collagen and lowered the protein expression of the transforming growth factor-beta (TGF-beta), extracellular signal-regulated kinases 1/2 (ERK1/2), and SMAD3. Protein expression of CD68 and CD3 had a positive correlation with an area of aortic lumen (r(2) = 0.36; p < 0.001), suggesting the importance of inflammation in the causative mechanisms of aortic dilation. Enhanced adenosine availability by LDEMTX was suggested by higher aortic expression of an anti-adenosine A2a receptor (A2a) and lower adenosine deaminase expression. Commercial MTX had negligible effects. LDEMTX prevented the development of MFS-associated aortic defects and can thus be a candidate for testing in clinical studies.
conferenceObject Methotrexate associated with a lipid core nanoparticle prevented the dilation and dissection of the aortic arch in mice with Marfan syndrome(2020) GUIDO, M. C.; LOPES, N. M.; I, C. Albuquerque; TAVARES, E. R.; JENSEN, L.; V, L. Pereira; KALIL-FILHO, R.; LAURINDO, F. R. M.; MARANHAO, R. C.bookPart Regressão da aterosclerose: papel dos agentes proliferativos(2022) GOMES, Fernando L. T.; TAVARES, Elaine Rufo; MARANHãO, Raul Cavalcante