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
12 resultados
Resultados de Busca
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- 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 Effect of exercise training on HDL subclasses and cholesterol transfers to HDL in elderly individuals(2022) BRAGA, P. G. Senger; TAVONI, T. M.; BARONI, R. V.; ALDIN, M. N.; ALVES, M. J. N. N.; ROCHA, G. A.; BACHI, A. L. L.; NEGRAO, C. E.; VAISBERG, M. W.; FREITAS, F. R.; FIGUEIREDO NETO, A. M.; DAMASCENO, N. R. T.; MARANHAO, R. 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
- Intraoperative paclitaxel associated with lipid nanoparticles in trabeculectomy(2023) OCCHIUTTO, Marcelo L.; PASSOS, Thais H. M.; FREITAS, Fatima R.; MARANHAO, Raul C.; COSTA, Vital P.
- Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study(2024) MARINHO, Lucas Lage; RACHED, Fabiana Hanna; MORIKAWA, Aleksandra Tiemi; TAVONI, Thauany Martins; CARDOSO, Ana Paula Toniello; TORRES, Roberto Vitor Almeida; JR, Antonildes Nascimento Assuncao; JR, Carlos Vicente Serrano; NOMURA, Cesar Higa; MARANHAO, Raul CavalcanteIntroduction Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease.Methods We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment.Results Forty patients aged 65.6 +/- 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed.Conclusion In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers.Clinical Trial Registration https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
conferenceObject Methotrexate associated with nanoparticles decreases NLRC4 inflammasome expression in infarcted rat hearts(2023) GATTO, M.; MOTA, G. A. F.; BORIM, P. A.; SANTOS, A. C. C.; PAGAN, L. U.; SOUZA, L. M.; RODRIGUES, E. A.; SILVA, R. C. F.; OLIVEIRA, J. P. G.; MEIRELLES, A. L. B.; BROSLER, J. Y.; MARANHAO, R. C.; ZORNOFF, L. A. M.; OKOSHI, K.; OKOSHI, M. P.- Changes in serum amyloid A, plasma high- density lipoprotein cholesterol and apolipoprotein A- I as useful biomarkers for Mycobacterium tuberculosis infection(2023) FONTES, Cleuber Franco; BIDU, Nadielle Silva; FREITAS, Fatima Rodrigues; MARANHAO, Raul Cavalcante; MONTEIRO, Adriano de Souza Santos; COUTO, Ricardo David; NETTO, Eduardo MartinsIntroduction. In recent years, cholesterol has received interest in the study of infection due to evidence of a relationship between low plasma cholesterol levels and tuberculosis (TB). Hypothesis/Gap Statement. Plasma lipid profiles of serum amyloid A (SAA), apolipoprotein A -I and high-density lipoprotein cholesterol (HDL- C) are biomarkers associated with symptomatic TB patients. Objective. We aimed to evaluate plasma lipid profiles of apolipoprotein A -I, SAA and the size of HDL as biomarkers to diagnose symptomatic TB patients. Methodology. Patients with TB symptoms attending the Instituto Brasileiro para a Investigacao da Tuberculose/Fundacao Jose Silveira (IBIT/FJS) between September 2015 and August 2016 for diagnosis of TB were studied. From 129 patients, 97 were classified as pulmonary TB and 32 as negative-bacilloscopy (non -TB group). Medical history, fasting serum and plasma were obtained. Total cholesterol (TC), HDL- C, apolipoprotein A -I and SAA were measured by enzymatic or immunochemical reaction assays. HDL size was measured by laser light-scattering. Results. In TB patients, TC (147.0 & PLUSMN;37 vs. 168 & PLUSMN;44 mg dL-1), HDL- C (37 & PLUSMN;14 vs. 55 & PLUSMN;18 mg dL-1) and apolipoprotein A -I (102 & PLUSMN;41 vs. 156 & PLUSMN;47 mg dL-1) concentrations were lower (P<0.0001), while HDL particle size (10.16 & PLUSMN;1.02 vs. 9.62 & PLUSMN;0.67 nm) and SAA levels (280 & PLUSMN;36 vs. 19 & PLUSMN;8 mg L-1) were higher (P<0.0001). Using receiver-operating characteristic curve analysis for predicting TB, the cutoff values were <83.85 mg L-1 for SAA (sensitivity=96.88 %, specificity=78.43 %, P<0.0001), >44.50 mg dL-1 for HDL- C (sensitivity=75%, specificity=72.16%, P<0.001) and >118.5 mg dL-1 for apolipoprotein A -I (sensitivity=83.83 %, specificity=72.22 %, P<0.001). Conclusion. SAA, HDL- C and apolipoprotein A -I are associated with TB infection and could be used as laboratory biomarkers, especially in patients who are negative for alcohol- acid-resistant bacilli.
conferenceObject Cardiovascular Disease Progression in Children With Homozygous Familial Hypercholesterolemia Despite Early Diagnosis on a Genetic Cascade Screening Program(2022) JULIANI, Fabiana C.; CHACRA, Ana Paula M.; MINAME, Marcio H.; SALGADO FILHO, Wilson; MIZUTA, Marjorie H.; JANNES, Cinthia E.; KRIEGER, Jose E.; MARANHAO, Raul C.; SANTOS, Raul D.; ROCHA, Viviane Z.- Impact of high cholesterol intake on tissue cholesterol content and lipid transfers to high-density lipoprotein(2011) OLIVEIRA, Tatiane V.; MANIERO, Fernanda; SANTOS, Marilia H. H.; BYDLOWSKI, Sergio P.; MARANHAO, Raul C.Objective: Esterified cholesterol is the storage form of from in the organism. High-density lipoprotein (HDL), where free cholesterol is transferred from other lipoproteins and tissues, is the main esterification site in plasma. The aim of this study was to investigate how high cholesterol intake changes freer esterified ratios of cholesterol in the plasma, aorta, liver and lipid transfers to HDL. Methods: Twenty male Golden Syrian hamsters fed 0.5% cholesterol for 15 wk and 19 controls without cholesterol feeding were sacrificed to determine serum lipids, transfer proteins (cholestexyl ester transfer protein and phospholipid transfer protein), and amount of free and esterified cholesterol in the aorta and liver. In vitro transfer of radioactive free and esterified cholesterol, phospholipids, and triacylglycerols to HDL was performed by incubating whole plasma with an artificial nanoemulsion used as a lipid donor and measuring radioactivity in the HDL fraction after chemical precipitation of non-HDL fractions and of the nanoemulsion. Results: Compared with controls, cholesterol-fed animals showed a 137% increase in non-HDL plasma fraction and a 61% increase in HDL (P < 0.001). The esterined/free cholesterol ratio in non-HDL and HDL fractions did not change. In the aorta, free cholesterol increased 55% and the esterified/free ratio (0.2) decreased. Cholesterol accumulation in the liver was several-fold greater and esterified free increased (1.3). Cholesterol feeding pronouncedly increased the transfer of free and esterified cholesterol, phospholipids, and triacylglycerols to HDL and cholesteryl ester transfer protein and phospholipid transfer protein activities. Conclusions: Free cholesterol is cytotoxic and less stable than esterified cholesterol, and the present data on how the organism responds to high cholesterol intake with respect to esterified/free ratios in the plasma, aorta, liver, and lipid transfers to HDL may have physiopathologic implications.
conferenceObject LDE-paclitaxel in second or later lines in advanced pancreatic cancer: A phase I trial(2023) BIGHETTI, Bruna; MARANH, Raul Cavalcante; FORONES, Nora Manoukian