12 results on '"Gilberto M. Sperandio Da Silva"'
Search Results
2. Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): A study protocol for a randomized clinical trial
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Mauro F. F. Mediano, Leonardo G. Ribeiro, Rudson S. Silva, Isis G. G. Xavier, Marcelo C. Vieira, Tatiana R. Gonçalves, Vitor B. Paravidino, Juliana P. Borges, Luiz Fernando Rodrigues Junior, Henrique S. Costa, Michel S. Reis, Livia C. Liporagi-Lopes, Pablo Martinez-Amezcua, Paula S. Silva, Gilberto M. Sperandio Da Silva, Andrea S. Sousa, Marcelo T. Holanda, Henrique H. Veloso, Fernanda M. Carneiro, Flavia Mazzoli-Rocha, Andrea R. Costa, Roberto M. Saraiva, Fernanda S. N. S. Mendes, Luiz Henrique C. Sangenis, and Alejandro M. Hasslocher-Moreno more...
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physical activity ,exercise training ,mental health ,fitness ,Chagas disease ,quality of life ,Medicine (General) ,R5-920 - Abstract
BackgroundChagas disease (CD) is a neglected endemic disease with worldwide impact due to migration. Approximately 50–70% of individuals in the chronic phase of CD present the indeterminate form, characterized by parasitological and/or serological evidence of Trypanosoma cruzi infection, but without clinical signs and symptoms. Subclinical abnormalities have been reported in indeterminate form of CD, including pro-inflammatory states and alterations in cardiac function, biomarkers and autonomic modulation. Moreover, individuals with CD are usually impacted on their personal and professional life, making social insertion difficult and impacting their mental health and quality of life (QoL). Physical exercise has been acknowledged as an important strategy to prevent and control numerous chronic-degenerative diseases, but unexplored in individuals with the indeterminate form of CD. The PEDI-CHAGAS study (which stands for “Home-Based Exercise Program in the Indeterminate Form of Chagas Disease” in Portuguese) aims to evaluate the effects of a home-based exercise program on physical and mental health outcomes in individuals with indeterminate form of CD.Methods and designThe PEDI-CHAGAS is a two-arm (exercise and control) phase 3 superiority randomized clinical trial including patients with indeterminate form of CD. The exclusion criteria are more...
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- 2023
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Catalog
3. The association of exercise test variables with long-term mortality in patients with chronic Chagas disease
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Rudson S. Silva, Fernanda S. N. S. Mendes, Jerome L. Fleg, Luiz F. Rodrigues Junior, Marcelo C. Vieira, Isis G. G. Xavier, Henrique S. Costa, Michel S. Reis, Flavia Mazzoli-Rocha, Andrea R. Costa, Marcelo T. Holanda, Henrique H. Veloso, Gilberto M. Sperandio da Silva, Andréa S. Sousa, Roberto M. Saraiva, Alejandro Marcel Hasslocher-Moreno, and Mauro F. F. Mediano more...
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Chagas disease ,mortality ,prognosis ,VO2max ,maximal functional capacity ,Medicine (General) ,R5-920 - Abstract
BackgroundThe identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD.MethodsThis retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality.ResultsThere were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25–75% 8.0–27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00–1.03 per mmHg) and change (HR 1.03; 95% CI 1.01–1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14–13.74), during exercise (HR 2.73; 95% CI 1.44–5.20), and recovery (HR 2.60; 95% CI 1.14–5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33–3.21).ConclusionOur findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD. more...
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- 2022
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4. Effects of Selenium treatment on cardiac function in Chagas heart disease: Results from the STCC randomized Trial
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Marcelo T. Holanda, Mauro F.F. Mediano, Alejandro M. Hasslocher-Moreno, Beatriz M.S. Gonzaga, Anna Cristina C. Carvalho, Roberto R. Ferreira, Luciana R. Garzoni, Fernanda S. Pereira-Silva, Luis O. Pimentel, Marcelo O. Mendes, Marcos J. Azevedo, Constança Britto, Otacilio C. Moreira, Alice G. Fernandes, Carolina M. Santos, Jéssica Constermani, Vitor B. Paravidino, Erica R. Maciel, Fernanda M. Carneiro, Sérgio S. Xavier, Gilberto M. Sperandio da Silva, Priscila F. Santos, Henrique H. Veloso, Pedro E.A.A. Brasil, Andrea S. de Sousa, Maria G. Bonecini-de-Almeida, Paula S. da Silva, Luiz Henrique C. Sangenis, Roberto M. Saraiva, and Tania C. Araujo-Jorge more...
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Medicine (General) ,R5-920 - Abstract
Background: Chagas disease (caused by Trypanosoma cruzi infection) evolves to chronic chagasic cardiomyopathy (CCC) affecting 1.8 million people worldwide. This is the first randomized, placebo-controlled, double-blinded, clinical trial designed to estimate efficacy and safety of selenium (Se) treatment in CCC. Methods: 66 patients with CCC stages B1 (left ventricular ejection fraction [LVEF] > 45% and no heart failure; n = 54) or B2 (LVEF < 45% and no heart failure; n = 12) were randomly assigned to receive 100 mcg/day sodium selenite (Se, n = 32) or placebo (Pla, n = 34) for one year (study period: May 2014-September 2018). LVEF changes over time and adverse effects were investigated. Trial registration number: NCT00875173 (clinicaltrials.gov). Findings: No significant differences between the two groups were observed for the primary outcome: mean LVEF after 6 (β= +1.1 p = 0.51 for Se vs Pla) and 12 months (β= +2.1; p = 0.23). In a subgroup analysis, statistically significant longitudinal changes were observed for mean LVEF in the stage B2 subgroup (β= +10.1; p = 0.02 for Se [n = 4] vs Pla [n = 8]). Se treatment was safe for CCC patients, and the few adverse effects observed were similarly distributed across the two groups. Interpretation: Se treatment did not improve cardiac function (evaluated from LVEF) in CCC. However, in the subgroup of patients at B2 stage, a potential beneficial influence of Se was observed. Complementary studies are necessary to explore diverse Se dose and/or associations in different CCC stages (B2 and C), as well as in A and B1 stages with longer follow-up. Funding: Brazilian Ministry of Health, Fiocruz, CNPq, FAPERJ. more...
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- 2021
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5. The Saga of Selenium Treatment Investigation in Chagas Disease Cardiopathy: Translational Research in a Neglected Tropical Disease in Brazil
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Tania C. de Araujo-Jorge, Anna Cristina C. Carvalho, Roberto R. Ferreira, Luciana R. Garzoni, Beatriz M.S. Gonzaga, Marcelo T. Holanda, Gilberto M. Sperandio da Silva, Maria da Gloria Bonecini-Almeida, Mauro F.F. Mediano, Roberto M. Saraiva, and Alejandro M. Hasslocher-Moreno more...
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This chapter describes the steps from basic research to the definition of a putative public health recommendation in the clinical protocols and therapeutic guidelines for selenium (Se) supplementation for patients with Chagas disease. From 1998 to 2018, we conducted a translational research project to test the concept that chronic Chagas disease cardiopathy (CCC) severity could be associated with low levels of blood selenium (Se), and if oral Se supplementation could help to sustain the asymptomatic cardiac stage and reduce disease severity. Pre-clinical studies in mice and a clinical trial conducted in the early asymptomatic cardiac stage of CCC patients (B stage) were performed, identified as “Selenium Treatment of Chagasic Cardiopathy (STCC)” trial. The roadmap of the selenium project was/is a real saga, with important obstacles that tested team resilience and revealed Brazilian conditions of science development. We discuss the main possible mechanisms involved in the physiopathology of CCC and the lessons learned in this process. In this chapter, we also organized the timeline of the translational project and described the crucial moments of the journey, as well as the next steps driving the research teams and their international and health industry connections. more...
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- 2022
6. Synthesis and characterization of the atropisomeric relationships of a substituted N-phenyl-bipyrazole derivative with anti-inflammatory properties
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Nelilma C. Romeiro, Helio de M. Alves, Eliezer J. Barreiro, Carlos A. M. Fraga, Ana L.P. Miranda, Javier Ellena, Marcia Paranho Veloso, Antonio C. Doriguetto, and Gilberto M. Sperandio da Silva
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Pharmacology ,Lanthanide ,Atropisomer ,Molecular model ,Stereochemistry ,medicine.drug_class ,Chemistry ,Organic Chemistry ,Catalysis ,Anti-inflammatory ,Analytical Chemistry ,Characterization (materials science) ,Axial chirality ,Drug Discovery ,medicine ,Chirality (chemistry) ,Spectroscopy - Abstract
This work describes the atropisomeric relationships of 3-methyl-5-(3-methyl-5-phenyl-1H-pyrazol-1-yl)-1-phenyl-1H-pyrazol-4-amine (2d), which belongs to series 4-aminobipyrazole derivatives designed as anti-inflammatory agents. The 1H nuclear magnetic resonance spectra obtained in the presence of a chiral lanthanide shift salt associated to chiral high-performance liquid chromatography analysis, X-ray diffraction, and molecular modeling tools confirmed that ortho bis-functionalized bipyrazole 2d exists as a mixture of aR,aS-atropisomers. These results provide useful information to understand the pharmacological profile of this derivative and of other 4-aminobipyrazole analogs. Chirality 24:463–470, 2012. © 2012 Wiley Periodicals, Inc. more...
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- 2012
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7. The Molecular Basis of COX-2 Versus COX-1 Selectivity of Lumiracoxib by Molecular Docking Studies
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Carlos A. M. Fraga, Celia M. Correa, Eliezer J. Barreiro, Andre F. de Paula, Gilberto M. Sperandio da Silva, and Carlos Mauricio R. Sant'Anna
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Chemistry ,Stereochemistry ,Drug Discovery ,medicine ,Pharmaceutical Science ,Molecular Medicine ,Lumiracoxib ,Selectivity ,medicine.drug - Published
- 2007
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8. A proposed molecular basis for the selective resveratrol inhibition of the PGHS-1 peroxidase activity
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Eliezer J. Barreiro, Carlos A. M. Fraga, Arthur Eugen Kümmerle, Carlos Mauricio R. Sant'Anna, and Gilberto M. Sperandio da Silva
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Models, Molecular ,Steric effects ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Resveratrol ,Biochemistry ,Substrate Specificity ,chemistry.chemical_compound ,Stilbenes ,Drug Discovery ,Cyclooxygenase Inhibitors ,Binding site ,Molecular Biology ,Heme ,Binding Sites ,biology ,Chemistry ,Organic Chemistry ,Active site ,Protein Structure, Tertiary ,Peroxidases ,Enzyme inhibitor ,Docking (molecular) ,Cyclooxygenase 1 ,biology.protein ,Molecular Medicine ,Peroxidase - Abstract
Docking results have enabled us to propose how resveratrol could act as a selective PGHS-1 peroxidase site inhibitor. The docking model has predicted a slightly less favorable DeltaG(bind) (-17.9 kcal/mol) of the resveratrol to the PGHS-2 peroxidase site in comparison with its corresponding binding to the PGHS-1 (-20.4 kcal/mol). The formation of hydrogen bonds among the hydroxyl groups of the resveratrol phenyl rings, the backbone of Fe-heme and the carbonyl group of Leu294 inside the PGHS-1 peroxidase site, associated with the absence of His214 in the backbone of PGHS-1, are essential features that are required to maintain the aromatic rings of the natural product parallel to the Fe-heme group and transverse to the peroxidase access channel promoting a large steric hindrance at this site and its consequent selective inhibition. more...
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- 2005
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9. The molecular basis for coxib inhibition of p38α MAP kinase
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Carlos A. M. Fraga, Lídia Moreira Lima, Gilberto M. Sperandio da Silva, Eliezer J. Barreiro, and Carlos Mauricio R. Sant'Anna
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Databases, Factual ,Molecular model ,Stereochemistry ,Clinical Biochemistry ,Quantitative Structure-Activity Relationship ,Pharmaceutical Science ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Drug Discovery ,Cyclooxygenase Inhibitors ,Enzyme Inhibitors ,Binding site ,Protein kinase A ,Molecular Biology ,Cyclooxygenase 2 Inhibitors ,biology ,Chemistry ,Kinase ,Organic Chemistry ,Enzyme Activation ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Docking (molecular) ,Enzyme inhibitor ,Mitogen-activated protein kinase ,biology.protein ,Molecular Medicine ,Signal transduction ,Algorithms ,Protein Binding - Abstract
In this work, we present the results of two combined approaches, molecular docking and comparative molecular field analysis (CoMFA), to propose how the selective cyclooxygenase-2 inhibitor celecoxib could act as a p38 mitogen-activated protein (MAP) kinase inhibitor. The docking analysis revealed why celecoxib has a less favorable binding energy (DeltaG= -12.4kcal/mol) than the selective p38 MAP kinase (p38 MAPK) inhibitor, SB203580 (DeltaG= -22.2kcal/mol). The CoMFA results revealed unfavorable steric effects that can be related to the predicted lower p38 MAP kinase inhibitory activity of celecoxib. Additionally, FlexX and CoMFA results also suggested that etoricoxib, another selective COX-2 inhibitor, could inhibit p38 MAP kinase. more...
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- 2005
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10. A novel 3D-QSAR comparative molecular field analysis (CoMFA) model of imidazole and quinazolinone functionalized p38 MAP kinase inhibitors
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Gilberto M. Sperandio da Silva, Eliezer J. Barreiro, and Carlos Mauricio R. Sant'Anna
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Models, Molecular ,Quantitative structure–activity relationship ,Molecular model ,Stereochemistry ,Clinical Biochemistry ,Quantitative Structure-Activity Relationship ,Pharmaceutical Science ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Drug Discovery ,Partial least squares regression ,Imidazole ,Enzyme Inhibitors ,Protein kinase A ,Molecular Biology ,Quinazolinone ,Molecular Structure ,biology ,Bicyclic molecule ,Organic Chemistry ,Imidazoles ,Reproducibility of Results ,Models, Chemical ,chemistry ,Enzyme inhibitor ,Quinazolines ,biology.protein ,Molecular Medicine - Abstract
In this study we describe a new comparative molecular field analysis (CoMFA) model of dihydroquinazolinone and tetrasubstituted imidazole compounds with p38 MAPK inhibitory activity. A series of 51 (a training set of 40 and a test set of 11) dihydroquinazolinone [Bioorg. Med. Chem. Lett. 2003, 13, 277.] and tetrasubstituted imidazole [J. Med. Chem. 1999, 42, 2180.] derivatives known as p38 mitogen-activated protein kinase (p38 MAPK) selective inhibitors was studied by quantitative structure-activity relationship (3D-QSAR) analysis using comparative molecular field analysis. The 3D-QSAR models were generated and evaluated by a scheme that combines a genetic algorithm (GA) optimization with partial least squares (PLS) regression and by crossvalidation using the leave-one-out technique. The model was able to efficiently predict the activities of the compounds of the test set, suggesting that it can be used for the planning of new p38 MAPK inhibitor candidates useful to treat chronic inflammatory states. more...
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- 2004
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11. Development of new CoMFA and CoMSIA 3D-QSAR models for anti-inflammatory phthalimide-containing TNFalpha modulators
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Carlos Mauricio R. Sant'Anna, Carolina M. Avila, Eliezer J. Barreiro, Carlos A. M. Fraga, Gilberto M. Sperandio da Silva, and Nelilma C. Romeiro
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Models, Molecular ,Quantitative structure–activity relationship ,Molecular model ,Databases, Factual ,Stereochemistry ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Quantitative Structure-Activity Relationship ,Phthalimides ,Field analysis ,Biochemistry ,Anti-inflammatory ,Phthalimide ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Computer Simulation ,Molecular Biology ,Tumor necrosis factor α ,Binding Sites ,Molecular Structure ,Tumor Necrosis Factor-alpha ,Organic Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,chemistry ,Models, Chemical ,Reduced toxicity ,Drug Design ,Molecular Medicine ,Three dimensional model - Abstract
In the present study, we describe a new 3D-QSAR analysis of 42 previously reported thalidomide analogues, with the ability to modulate the pro-inflammatory cytokine TNFalpha, by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Three statistically significant models were obtained. The best resulting CoMFA and CoMSIA models have conventional r(2) values of 0.996 and 0.983, respectively. The cross-validated q(2) values are 0.869 and 0.868, respectively. The analysis of CoMFA and CoMSIA contour maps provided insight into the possible sites for structural modification of the thalidomide analogues for better activity and reduced toxicity. more...
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- 2006
12. Design, synthesis, and pharmacological evaluation of new neuroactive pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives with in vivo hypnotic and analgesic profile
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Carlos A. M. Fraga, Eliezer J. Barreiro, Juliana M Raimundo, Gilberto M. Sperandio da Silva, Roberto T. Sudo, Gisele Zapata-Sudo, and Ricardo Menegatti
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Male ,Models, Molecular ,Zolpidem ,medicine.drug_class ,Stereochemistry ,Pyridines ,Clinical Biochemistry ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Quantitative Structure-Activity Relationship ,Motor Activity ,Ligands ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Mice ,In vivo ,Drug Discovery ,Pyridine ,medicine ,Animals ,Hypnotics and Sedatives ,GABA-A Receptor Agonists ,Imide ,Molecular Biology ,GABA Agonists ,Benzodiazepine ,Chemistry ,Organic Chemistry ,Analgesics, Non-Narcotic ,Receptors, GABA-A ,Sedative ,Drug Design ,Molecular Medicine ,Sleep ,Lead compound ,medicine.drug - Abstract
The present study describes the synthesis and pharmacological profiles of four novel pyrazolo[3,4- b ]pyrrolo[3,4- d ]pyridine derivatives 2 – 5 , which were structurally designed by using the sedative and analgesic drug zolpidem 1 as lead compound. The heterotricyclic system present in the target compounds 2 – 5 was constructed in good yields, exploiting a regioselective hetero Diels–Alder reaction of the key azabutadiene derivative 7 and functionalized N -phenylmaleimides 9 – 12 . Additionally, we identified that 1-methyl-7-(4-nitrophenyl)-3-phenyl-3,6,7,8-tetrahydropyrazolo[3,4- b ]pyrrolo[3,4- d ]pyridine-6,8-dione derivative (LASSBio-873, 5 ) presented not only the most potent ability to promote sedation, which was similar to that induced by the standard benzodiazepine drug midazolam, but also potent central antinociceptive effect. more...
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- 2005
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