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1.
J. pediatr. (Rio J.) ; 99(2): 139-146, Mar.-Apr. 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1430711

RESUMO

Abstract Objective: To investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. Methods: A randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. Results: Heterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). Conclusion: Aerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents.

2.
J Pediatr (Rio J) ; 99(2): 139-146, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36030815

RESUMO

OBJECTIVE: To investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. METHODS: A randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. RESULTS: Heterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). CONCLUSION: Aerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents.


Assuntos
Doenças Cardiovasculares , Obesidade Infantil , Humanos , Adolescente , Sobrepeso , Índice de Massa Corporal , Fatores de Risco , Exercício Físico , Tecido Adiposo , Fatores de Risco de Doenças Cardíacas , Colesterol , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Polimorfismo de Nucleotídeo Único
3.
J Chem Inf Model ; 60(2): 731-737, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-31850756

RESUMO

The NS2B-NS3 protease has been identified as an attractive target for drug development against Zika virus (ZIKV) and combined drug repurposing and structure-based virtual screening has improved the development of antiviral drugs. In this study, we performed a structure-based virtual screening of 1861 Food and Administration (FDA) approved drugs available in DrugBank by the selection and docking validation of crystal structure of ZIKV NS2B-NS3 protease (PDB ID 5H4I ) using Glide and DOCK 6 software. The antihistaminic chlorcyclizine (Grid score -24.8 kcal/mol) exhibited the most promising interaction with NS2B-NS3 protease in comparison to crystallography ligand (Grid score -15.6 kcal/mol) by interaction to Tyr161 by hydrophobic interactions in the binding site of NS2B-NS3 which is recognized as an important amino acid in substrate molecular recognition. Cytotoxicity and global antiviral activity assay in Vero cells by MTT method showed that chlorcyclizine reduced the ZIKV induced cytopathic effect (EC50 of 69.0 ± 7.3 µM and SI = 1.9), and explicit molecular dynamics simulations implemented on a NAMD program indicated great stability of chlorcyclizine in protease binding site, suggesting the repurposing of chlorcyclizine as a promising finding in anti-ZIKV drug development.


Assuntos
Reposicionamento de Medicamentos , Simulação de Dinâmica Molecular , Inibidores de Serina Proteinase/química , Inibidores de Serina Proteinase/farmacologia , Proteínas Virais/antagonistas & inibidores , Zika virus/enzimologia , Animais , Chlorocebus aethiops , Conformação Proteica , Serina Endopeptidases/química , Inibidores de Serina Proteinase/toxicidade , Células Vero , Proteínas Virais/química
4.
Biotechnol Prog ; 33(3): 804-814, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28371522

RESUMO

Schistosomiasis is the second leading cause of death due to parasitic diseases in the world. Seeking an alternative for the control of disease, the World Health Organization funded the genome sequencing of the major species related to schistosomiasis to identify potential vaccines and therapeutic targets. Therefore, the aim of this work was to select T and B-cell epitopes from Schistosoma mansoni through computational analyses and evaluate the immunological potential of epitopes in vitro. Extracellular regions of membrane proteins from the Schistosoma mansoni were used to predict promiscuous epitopes with affinity to different human Major Histocompatibility Class II (MHCII) molecules by bioinformatics analysis. The three-dimensional structure of selected epitopes was constructed and used in molecular docking to verify the interaction with murine MHCII H2-IAb . In this process, four epitopes were selected and synthesized to assess their ability to stimulate proliferation of CD4+ T lymphocytes in mice splenocyte cultures. The results showed that Sm041370 and Sm168240 epitopes induced significant cell proliferation. Additionally, the four epitopes were used as antigens in the Indirect Enzyme-Linked Immunosorbent Assay (ELISA) to assess the recognition by serum from individuals infected with Schistosoma mansoni. Sm140560, Sm168240, and Sm041370 epitopes were recognized by infected individuals IgG antibodies. Therefore, Sm041370 and Sm168240 epitopes that stood out in in silico and in vitro analyses could be promising antigens in schistosomiasis vaccine development or diagnostic kits. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:804-814, 2017.


Assuntos
Epitopos/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Proliferação de Células/fisiologia , Biologia Computacional/métodos , Ensaio de Imunoadsorção Enzimática , Complexo Principal de Histocompatibilidade/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Schistosoma mansoni/imunologia
5.
Appl Biochem Biotechnol ; 179(6): 1023-40, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26979443

RESUMO

Schistosomiasis remains an important parasitic disease that affects millions of individuals worldwide. Despite the availability of chemotherapy, the occurrence of constant reinfection demonstrates the need for additional forms of intervention and the development of a vaccine represents a relevant strategy to control this disease. With the advent of genomics and bioinformatics, new strategies to search for vaccine targets have been proposed, as the reverse vaccinology. In this work, computational analyses of Schistosoma mansoni membrane proteins were performed to predict epitopes with high affinity for different human leukocyte antigen (HLA)-DRB1. Ten epitopes were selected and along with murine major histocompatibility complex (MHC) class II molecule had their three-dimensional structures optimized. Epitope interactions were evaluated against murine MHC class II molecule through molecular docking, electrostatic potential, and molecular volume. The epitope Sm141290 and Sm050890 stood out in most of the molecular modeling analyses. Cellular proliferation assay was performed to evaluate the ability of these epitopes to bind to murine MHC II molecules and stimulate CD4+ T cells showing that the same epitopes were able to significantly stimulate cell proliferation. This work showed an important strategy of peptide selection for epitope-based vaccine design, achieved by in silico analyses that can precede in vivo and in vitro experiments, avoiding excessive experimentation.


Assuntos
Proliferação de Células/genética , Epitopos/imunologia , Schistosoma mansoni/imunologia , Vacinas/imunologia , Animais , Epitopos/genética , Humanos , Proteínas de Membrana/imunologia , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Schistosoma mansoni/genética , Schistosoma mansoni/patogenicidade , Linfócitos T/imunologia , Vacinas/genética
6.
PLoS One ; 10(7): e0132852, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26197432

RESUMO

Iron is an essential chemical element for human life. However, in some pathological conditions, such as hereditary hemochromatosis type 1 (HH1), iron overload induces the production of reactive oxygen species that may lead to lipid peroxidation and a change in the plasma-membrane lipid profile. In this study, we investigated whether iron overload interferes with the Na,K-ATPase activity of the plasma membrane by studying erythrocytes that were obtained from the whole blood of patients suffering from iron overload. Additionally, we treated erythrocytes of normal subjects with 0.8 mM H2O2 and 1 µM FeCl3 for 24 h. We then analyzed the lipid profile, lipid peroxidation and Na,K-ATPase activity of plasma membranes derived from these cells. Iron overload was more frequent in men (87.5%) than in women and was associated with an increase (446%) in lipid peroxidation, as indicated by the amount of the thiobarbituric acid reactive substances (TBARS) and an increase (327%) in the Na,K-ATPase activity in the plasma membrane of erythrocytes. Erythrocytes treated with 1 µM FeCl3 for 24 h showed an increase (132%) in the Na,K-ATPase activity but no change in the TBARS levels. Iron treatment also decreased the cholesterol and phospholipid content of the erythrocyte membranes and similar decreases were observed in iron overload patients. In contrast, erythrocytes treated with 0.8 mM H2O2 for 24 h showed no change in the measured parameters. These results indicate that erythrocytes from patients with iron overload exhibit higher Na,K-ATPase activity compared with normal subjects and that this effect is specifically associated with altered iron levels.


Assuntos
Membrana Eritrocítica/metabolismo , Sobrecarga de Ferro/enzimologia , Lipídeos/sangue , ATPase Trocadora de Sódio-Potássio/sangue , Membrana Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/enzimologia , Feminino , Humanos , Peróxido de Hidrogênio/farmacologia , Sobrecarga de Ferro/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
7.
Am J Hum Biol ; 22(5): 716-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20737622

RESUMO

UNLABELLED: Estimates of allele frequencies for recessive diseases are generally based on the frequency of affected individuals (q(2)). However, these estimates can be strongly biased due to inbreeding in the population. OBJECTIVES: The purpose of this study was to gain a better understanding of how inbreeding in the Minas Gerais State population affects phenylketonuria (PKU) incidence in the state and to determine the inbreeding coefficient based on microsatellites. METHODS: Inbreeding coefficients of samples of 104 controls and 76 patients with PKU were estimated through a microsatellite approach. Besides, the amount and distribution of genetic variation within and among patients with PKU and control samples were characterized. RESULTS: No genetic differentiation was observed between the samples. However, the Fis value found for samples of patients with PKU (0.042) was almost 15 times higher than that found among controls (0.003). When corrected by the inbreeding coefficient found among the controls, the PKU allele frequency decreased to 0.0057. CONCLUSIONS: The results enables us to infer that at least 35% of the PKU recessive homozygotes from the Minas Gerais population could be due to consanguineous marriages and suggest that microsatellites can be an useful approach to estimate inbreeding coefficients.


Assuntos
Consanguinidade , Frequência do Gene , Repetições de Microssatélites/genética , Fenilcetonúrias/epidemiologia , Fenilcetonúrias/genética , Brasil/epidemiologia , Genes Recessivos , Marcadores Genéticos , Genética Populacional , Humanos , Incidência , Estatística como Assunto
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