RAUL CAVALCANTE MARANHAO
Projetos de Pesquisa
Unidades Organizacionais
FBC, FCF - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
24 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 24
conferenceObject LIPIDS TRANSFER TO HDL IN PATIENTS WITH HEART FAILURE WAS DIMINISHED AND IS CORRELATED WITH IL-6 AND BNP LEVELS(2017) MARTINE, Ana Elisa Marabini; CARVALHO, Priscila O.; CURIATTI, Milena N. C.; MIRANDA, Bruna O.; FREITAS, Fatima R.; KALIL FILHO, Roberto; BARRETTO, Antonio Carlos Pereira; MARANHAO, Raul C.- Organic effects of associating paclitaxel with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella(2017) FEIO, Danielle Cristinne Azevedo; OLIVEIRA, Nayara Cristina Lima de; PEREIRA, Edmundo Luis Rodrigues; MORIKAWA, Aleksandra Tiemi; MUNIZ, Jose Augusto Pereira Carneiro; MONTENEGRO, Raquel Carvalho; ALVES, Ana Paula Negreiros Nunes; LIMA, Patricia Danielle Lima de; MARANHAO, Raul Cavalcante; BURBANO, Rommel RodriguezLipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m(2)) and three with higher (250 mg/m(2)) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight-food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents.
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.- Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice(2017) DAMINELLI, Elaine N.; FOTAKIS, Panagiotis; MESQUITA, Carlos H.; MARANHAO, Raul C.; ZANNIS, Vassilis I.Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A-I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with H-3-cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p < 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA-I KO than in WT. In apoA-I transgenic mice, LDE clearance was lower than in apoA-I KO and than in apoA-I KO infusion with human HDL. Infusion of human HDL into the apoA-I KO mice resulted in higher LDE clearance than in the apoA-I transgenic mice (p < 0.05). In apoA-I KO and apoA-I KO infused human HDL, the liver uptake was greater than in WT animals and apoA-I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A-I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA-I also influences those processes.
- Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial(2017) MANSUR, Antonio P.; ROGGERIO, Alessandra; GOES, Marisa F. S.; AVAKIAN, Solange D.; LEAL, Dalila P.; MARANHAO, Raul C.; STRUNZ, Celia M. C.Background: Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population. Methods and results: Forty-eight healthy participants (24 women) aged 55-65 years were randomized to either 30 days of resveratrol administration (500 mg/day) or caloric restriction (1000 cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipoprotein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resveratrol and caloric restriction increased serum concentrations of Sirt1, from 1.06 +/- 0.71 to 5.75 +/- 2.98 ng/mL; p < 0.0001, and from 1.65 +/- 1.81 to 5.80 +/- 2.23 ng/mL; p < 0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment. Conclusions: Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The longterm impact of these interventions on atherosclerosis should be assessed.
conferenceObject Lipid transfer to HDL in patients with heart failure was diminished and is correlated with IL-6 levels(2017) MARTINELLI, A. E. Ana Elisa Marabini; MARANHAO, R. C.; CARVALHO, P. O.; CURIATI, M. N. C.; OLIVEIRA, B. M.; FREITAS, F. R.; PEREIRA-BARRETTO, A. C.conferenceObject METHOTREXATE CARRIED IN LIPID CORE NANOPARTICLES REDUCED THE INFARCTION SIZE AND IMPROVED LEFT VENTRICLE FUNCTION FOLLOWING ACUTE MYOCARDIUM INFARCTION INDUCED IN RATS(2017) MARANHAO, Raul Cavalcante; GUIDO, Maria Carolina; MARQUES, Alyne Franca; TAVARES, Elaine Rufo; BISPO, Deborah Lima; MELO, Marcelo Dantas Tavares De; LIMA, Aline Derisio; NICOLAU, Jose Carlos; SALEMI, Vera Maria; KALIL-FILHO, Roberto- Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model(2017) FIORELLI, A. I.; LOURENCO-FILHO, D. D.; TAVARES, E. R.; CARVALHO, P. O.; MARQUES, A. F.; GUTIERREZ, P. S.; MARANHAO, R. C.; STOLF, N. A. G.Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg.kg(-1).day(-1) orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.
conferenceObject DIFFERENCES IN LIPID TRANSFERS TO HDL BETWEEN PATIENTS WITH CORONARY ARTERIAL DISEASE WITH OR WITHOUT TYPE 2 DIABETES MELLITUS(2017) MARANHAO, Raul Cavalcante; TAVONI, Thauany Martins; LAVERDY NETO, Oscar Giese; SPRANDEL, Marilia Da Costa Oliveira; KALIL FILHO, Roberto; HUEB, Whady Armindo- Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles: a magnetic resonance imaging study(2017) LIMA, Aline D.; HUA, Ning; MARANHAO, Raul C.; HAMILTON, James A.Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel (4 mg/kg) while 7 controls received saline solution. On week 12 and 16, in vivo MRI of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction of atherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area (14%) and stenosis (22%) by MRI and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.
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