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1.
Cad Saude Publica ; 40(4): e00086823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695454

RESUMO

The aim was to analyze the perception of Brazilian federal judges on the implications of COVID-19 vaccination. A study was carried out with Brazilian federal judges, who received a survey designed with multiple-choice questions on COVID-19 vaccination, covering topics such as its mandatory aspect, the application of coercive measures, hesitation to vaccinate, priority groups, the duties of Brazilian Health Regulatory Agency (Anvisa, acronym in Portuguese), the role of the Judiciary branch, and immunity passports. A total of 254 out of 1,300 federal judges from all states responded to the survey. Most respondents have a Bachelor's degree or a specialization (59.1%) and have been judges for more than 10 years (63.8%). A great majority of the judges (87.7%) agree with vaccine mandates for adults and for children and adolescents (66.1%). Over 75% of judges believe that all levels of government can impose sanctions on those who refuse to get vaccinated. The judges trust vaccination 93% of the time, 56.1% reject anti-vaccination movements, and 75.2% believe that Anvisa duties should be respected. The Judiciary branch actions concerning the COVID-19 pandemic are approved by 62.6% of judges, and 88.2% support immunity passports. There is a direct connection among mandatory vaccination, trust in the vaccine, and the adoption of immunity passports. Most federal judges agree with vaccine mandates for children and adults, support the application of sanctions for vaccination refusal, disapprove of anti-vaccination movements, agree with Anvisa's duties, and support judicial intervention in relation to the COVID-19 pandemic.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinação , Humanos , Brasil , COVID-19/prevenção & controle , Vacinação/legislação & jurisprudência , Adulto , Feminino , Masculino , Inquéritos e Questionários , SARS-CoV-2 , Hesitação Vacinal , Pessoa de Meia-Idade , Governo Federal , Pandemias/prevenção & controle
2.
Org Biomol Chem ; 22(7): 1500-1513, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38294067

RESUMO

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC50 values between 1.4 and 7.5 µM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.


Assuntos
Antineoplásicos , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/química , Ciclização , Imidazóis/farmacologia , Purinas/farmacologia , Amidinas/farmacologia , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células
3.
Cad. Saúde Pública (Online) ; 40(4): e00086823, 2024. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557409

RESUMO

Abstract: The aim was to analyze the perception of Brazilian federal judges on the implications of COVID-19 vaccination. A study was carried out with Brazilian federal judges, who received a survey designed with multiple-choice questions on COVID-19 vaccination, covering topics such as its mandatory aspect, the application of coercive measures, hesitation to vaccinate, priority groups, the duties of Brazilian Health Regulatory Agency (Anvisa, acronym in Portuguese), the role of the Judiciary branch, and immunity passports. A total of 254 out of 1,300 federal judges from all states responded to the survey. Most respondents have a Bachelor's degree or a specialization (59.1%) and have been judges for more than 10 years (63.8%). A great majority of the judges (87.7%) agree with vaccine mandates for adults and for children and adolescents (66.1%). Over 75% of judges believe that all levels of government can impose sanctions on those who refuse to get vaccinated. The judges trust vaccination 93% of the time, 56.1% reject anti-vaccination movements, and 75.2% believe that Anvisa duties should be respected. The Judiciary branch actions concerning the COVID-19 pandemic are approved by 62.6% of judges, and 88.2% support immunity passports. There is a direct connection among mandatory vaccination, trust in the vaccine, and the adoption of immunity passports. Most federal judges agree with vaccine mandates for children and adults, support the application of sanctions for vaccination refusal, disapprove of anti-vaccination movements, agree with Anvisa's duties, and support judicial intervention in relation to the COVID-19 pandemic.


Resumo: O objetivo foi analisar a visão de juízes federais brasileiros sobre as implicações da vacinação contra a COVID-19. Foi realizado um estudo com juízes federais brasileiros, que receberam uma pesquisa elaborada com questões de múltipla escolha sobre a vacinação contra a COVID-19, abordando temas como sua obrigatoriedade, aplicação de medidas coercitivas, hesitação vacinal, grupos prioritários, ações da Agência Nacional de Vigilância Sanitária (Anvisa), o papel do Poder Judiciário e os passaportes de imunidade. Responderam à pesquisa 254 dos 1.300 juízes federais atuantes em todos os estados. A maioria dos entrevistados possui bacharelado ou especialização (59,1%) e atua como juiz há mais de 10 anos (63,8%). Grande parte dos juízes (87,7%) concorda com a obrigatoriedade da vacina para adultos e crianças e adolescentes (66,1%). Mais de 75% dos juízes acreditam que todos os níveis de governo podem impor sanções para aqueles que se recusam a ser vacinados. 93% dos juízes confiam na vacinação, 56,1% rejeitam movimentos antivacinação e 75,2% acreditam que as ações da Anvisa devem ser respeitadas. As ações do Judiciário referentes à pandemia da COVID-19 são aprovadas por 62,6% dos juízes e 88,2% apoiam passaportes de imunidade. Existe uma ligação direta entre a vacinação obrigatória, a confiança na vacina e a adoção de passaportes de imunidade. A maioria dos juízes federais concorda com a obrigatoriedade da vacina para crianças e adultos, apoia a aplicação de sanções no caso de recusa de vacinação, desaprova movimentos antivacinação, concorda com as ações da Anvisa e apoia a intervenção do Judiciário em relação à pandemia da COVID-19.


Resumen: El objetivo fue analizar la visión de los jueces federales brasileños sobre las implicaciones de la vacunación contra la COVID-19. Se realizó un estudio con jueces federales brasileños, quienes recibieron una encuesta elaborada con preguntas de opción múltiple sobre la vacunación contra la COVID-19, abordando temas como su obligatoriedad, aplicación de medidas coercitivas, reticencia a vacunarse, grupos prioritarios, acciones de Agência Nacional de Vigilancia Sanitaria (Anvisa), el papel del Poder Judicial y los pasaportes de inmunidad. Respondieron a la encuesta 254 de los 1.300 jueces federales que actúan en todos los estados. La mayoría de los encuestados tiene título de licenciatura o especialización (59,1%) y actúa como juez desde hace más de 10 años (63,8%). Gran parte de los jueces (87,7%) está de acuerdo con la obligatoriedad de la vacuna para adultos y niños y adolescentes (66,1%). Más del 75% de los jueces cree que todos los niveles de gobierno pueden imponer sanciones a quienes se nieguen a vacunarse. El 93% de los jueces confía en la vacunación, el 56,1% rechaza los movimientos antivacunas y el 75,2% cree que las acciones de Anvisa deben ser respetadas. Las acciones del Poder Judicial con relación a la pandemia de COVID-19 son aprobadas por el 62,6% de los jueces, y el 88,2% apoya los pasaportes de inmunidad. Existe un vínculo directo entre la vacunación obligatoria, la confianza en la vacuna y la adopción de pasaportes de inmunidad. La mayoría de los jueces federales está de acuerdo con la vacunación obligatoria para niños y adultos, apoya la aplicación de sanciones en caso de rechazo de la vacunación, desaprueba los movimientos antivacunas, está de acuerdo con las acciones de Anvisa y apoya la intervención del Poder Judicial con relación a la pandemia de COVID-19.

4.
Braz J Microbiol ; 54(2): 761-768, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37160839

RESUMO

To maintain asepsis in production environments, contamination must be constantly controlled. To this end, microbiological monitoring is constantly used with the objective of evaluating the incidence of microorganisms prevalent in the sampling of air, surface, and people, in the area of an environment considered aseptic, isolated, and identified using the rapid and automated phenotypic microbiological methodology, highlighting the MALDI-TOF mass spectrometry analysis technique (MS), being identified at the level of genus and/or species. For that purpose, microbiological control of environmental monitoring of environments considered aseptic in a pharmaceutical industry was conducted for 12 months. The isolated microorganisms were identified using the mass spectrometry identification method (MALDI-TOF). In area classification A, the most prevalent microorganisms were bacteria in the sampling person. The microbial population was composed of bacteria of the genus Micrococcus sp. and Staphylococcus sp. Based on the results, it is possible to observe that in an environment where the process requires human operations, possible microbial contamination is inevitable and requires the identification of microorganisms at least at the level of species and/or genus. The microorganisms identified and found in the sampling of the aseptic environment must be evaluated with frequency to ensure that the productive environment guarantees the quality of the product produced.


Assuntos
Bactérias , Staphylococcus , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Técnicas Microbiológicas/métodos
5.
Cells ; 11(24)2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36552844

RESUMO

Cancer is one of the leading causes of death worldwide, thus the search for new cancer therapies is of utmost importance. Ursolic acid is a naturally occurring pentacyclic triterpene with a wide range of pharmacological activities including anti-inflammatory and anti-neoplastic effects. The latter has been assigned to its ability to promote apoptosis and inhibit cancer cell proliferation by poorly defined mechanisms. In this report, we identify lysosomes as the essential targets of the anti-cancer activity of ursolic acid. The treatment of MCF7 breast cancer cells with ursolic acid elevates lysosomal pH, alters the cellular lipid profile, and causes lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol. Lysosomal membrane permeabilization precedes the essential hallmarks of apoptosis placing it as an initial event in the cascade of effects induced by ursolic acid. The disruption of the lysosomal function impairs the autophagic pathway and likely partakes in the mechanism by which ursolic acid kills cancer cells. Furthermore, we find that combining treatment with ursolic acid and cationic amphiphilic drugs can significantly enhance the degree of lysosomal membrane permeabilization and cell death in breast cancer cells.


Assuntos
Neoplasias da Mama , Lisossomos , Humanos , Feminino , Lisossomos/metabolismo , Homeostase , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Lipídeos/farmacologia , Ácido Ursólico
6.
World J Gastrointest Oncol ; 14(6): 1115-1123, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35949218

RESUMO

Activating mutations in the oncogenes KRAS, BRAF and PI3K define molecular colorectal cancer (CRC) subtypes because they play key roles in promoting CRC development and in determining the efficacy of chemotherapeutic agents such as 5-fluorouracil and anti-epidermal growth factor receptor monoclonal antibodies. Survival of patients with cancers displaying these molecular profiles is low. Given the limited efficacy of therapeutic strategies for CRC presenting mutational activations in mitogen-activated protein kinase and/or PI3K pathways, developing combination therapies with natural flavonoids or other phytochemicals with demonstrated effects on these pathways (and little or no toxic effects) may constitute a valuable path forward. Much has been published on the anticancer effects of dietary phytochemicals. However, even an exhaustive characterization of potential beneficial effects produced by in vitro studies cannot be extrapolated to effects in humans. So far, the available data constitute a good starting point. Published results show quercetin and curcumin as possibly the best candidates to be further explored in the context of adjuvant CRC therapy either as part of dietary prescriptions or as purified compounds in combination regimens with the drugs currently used in CRC treatment. Clinical trial data is still largely missing and is urgently needed to verify relevant effects and for the development of more personalized treatment approaches.

9.
Foods ; 9(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806531

RESUMO

Vine pruning residues are by-products of the wine industry that have not received much attention in the past, in spite of being rich in bioactive compounds. In this study, we aimed to test whether an ohmic extract of vine pruning residue (VPE) has anti-colorectal cancer (CRC) properties, and whether responses differ according with cell's mutation profile. VPE decreased human CRC cell proliferation, accompanied by DNA effects and cell cycle modulation. VPE also increased cell sensitivity to the chemotherapeutic drug 5-FU. Our results suggest that tumors harboring BRAF mutations may be more responsive to VPE than KRAS mutated tumors. These effects of the extract were not completely reproduced by the most abundant constituents tested individually at the concentrations present in the effective dose of VPE. Globally, our results indicate that VPE, a polyphenol enriched extract produced by ohmic heating of vine pruning residue, has anti-colorectal cancer potential, including sensitizing to a chemotherapeutical drug, and its use in functional foods or nutraceuticals could be exploited in personalized anti colorectal cancer dietary strategies. Valorization of this lignocellulosic residue should encourage bio-waste recycling, adding value to this agricultural by-product and promoting the sustainable use of natural resources.

10.
Foods ; 9(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630276

RESUMO

Legumes are a rich source of a wide range of compounds that may represent an important tool to overcome gut dysbiosis. In this work, the prebiotic potential of two cooked legumes (cowpea and black bean) was investigated in comparison with potato:beef mixture, as substrates in batch faecal culture fermentation. Prior to the fermentation, all the samples were in vitro digested, passing through three phases, namely mouth, gastric and small intestine simulation, and then in vitro fermented for 6, 24 and 48 h. The shift of pH, production of gas and short-chain fatty acids (SCFAs) and changes in gut microbiota were evaluated along the fermentation time. The pH decreased significantly over time in all media with fermentable sources when compared with the negative control. Gas production was higher in the media containing fermentable source than in the negative control and decreased with fermentation time. The concentration of SCFAs increased over time and it was significantly higher for both legumes than in inulin (positive control) and potato:beef meal. Acetate was the major SCFAs produced during fermentation, particularly in media containing legumes. Both legumes presented a strong prebiotic effect on gut microbiota, showing a significant increase in Bifidobacterium and Lactobacillus. These results suggest that consumption of cooked cowpea and black bean, used alone or as an ingredient of novel functional foods, may contribute to improving intestinal health and therefore human health promotion.

11.
Biosci. j. (Online) ; 36(4): 1422-1428, 01-06-2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1147311

RESUMO

During the application of phytosanitary products in coffee trees, workers may be exposed to temperatures that could compromise their health. Exposure to occupational heat can lead to progressive dehydration, cramps, exhaustion and the possibility of thermal shock. Thus, knowing the levels of occupational heat that workers are exposed becomes important. This study aimed to evaluate workers' occupational exposure to heat during the application of phytosanitary products with manual costal pump in the coffee crops. The case study was developed at the IFSULDEMINAS school farm - Campus Inconfidentes in the months of September and October 2017. The occupational heat in the coffee crop was evaluated using the WBGTAVERAGE method, using TGD 400 thermal stress meter. The WBGT values found were compared to the exposure limits of NR 15 for the purposes of insalubrity classification and with NHO 06 for acclimatized and non-acclimatized workers. The results showed that the WBGT found is below the tolerance limit of NR 15, for the month of September. In October, the tolerance limit was exceeded in the period from 11:00 a.m. to 2:59 p.m., considering a continuous heavy activity and rest in the workplace, and the activity considered unhealthy. Considering the criteria of the NHO 06 it was observed that the limits of occupational exposure were exceeded in the month of October, for acclimatized and non-acclimatized workers. In September the occupational exposure limit of NHO 06 was exceeded only for non-acclimated workers. Therefore, the workers should be submitted to acclimatization during the phytosanitary application activity in the month of October.


Durante a aplicação de produtos fitossanitários no cafeeiro os trabalhadores podem estar expostos a temperaturas capazes de comprometer sua saúde. Exposição ao calor ocupacional pode levar a desidratação progressiva, câimbras, exaustão e possibilidade de choque térmico. Desta forma, conhecer os níveis de calor ocupacional que os trabalhadores estão expostos torna-se importante. O presente estudo teve como objetivo avaliar a exposição ocupacional ao calor de trabalhadores durante a aplicação de produtos fitossanitários com bomba costal manual na cultura do cafeeiro. O estudo de caso foi desenvolvido na fazenda-escola do IFSULDEMINAS ­ Campus Inconfidentes nos meses de setembro e outubro de 2017. Avaliou-se o calor ocupacional em lavoura cafeeira através do método do IBUTGMÉDIO, utilizando medidor de estresse térmico TGD 400. Os valores do IBUTG encontrados foram comparados aos limites de exposição da NR 15 para fins de classificação de insalubridade e com a NHO 06 para trabalhadores aclimatizados e não aclimatizados. Os resultados demostraram que o IBUTG encontrado está abaixo do limite de tolerância da NR15, para o mês de setembro. No mês de outubro o limite de tolerância foi ultrapassado no período das 11:00 às 14:59h, considerando uma atividade pesada contínua e descanso no próprio local de trabalho, sendo a atividade considerada insalubre. Ao considerarmos os critérios da NHO 06 observou-se que os limites de exposição ocupacional foram ultrapassados no mês de outubro, para trabalhadores aclimatizados e não aclimatizados. Em setembro o limite de exposição ocupacional da NHO 06 foi superado somente para trabalhadores não aclimatizados. Portanto os trabalhadores devem ser submetidos à aclimatização durante a atividade de aplicação de fitossanitários no mês de outubro.


Assuntos
Saúde Ocupacional , Temperatura Alta
12.
Food Chem ; 316: 126298, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32062230

RESUMO

Vine Pruning residue was submitted to conventional heating and ohmic heating (OH) for the extraction of bioactive compounds and analyzed for total phenolic content (TPC), polyphenolic profile, antioxidant activity, antimicrobial activity and anticancer activity. The OH extracts were obtained using Low electric field (496.0 V/cm) or Intermediate electric field - IEF (840.0 V/cm). The tests were performed using 45% (v/v) ethanol-water extraction solution at 80 °C at different extraction times (20-90 min). The extract that stood out among the others concerning anticancer potential was the one obtained by OH when used, IEF, where the TPC was significantly higher than in the other extracts which correlated with higher antioxidant, antimicrobial and anti-proliferative activity on different tumor cell lines (HepG2, MDA-MB-231, MCF-7 and Caco2). Vine pruning OH extracts obtained using green solvents by an eco-friendly procedure were revealed as a source of compounds with relevant antioxidant and anticancer activity.


Assuntos
Antioxidantes/química , Extratos Vegetais/química , Polifenóis/química , Vitis/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Temperatura Alta , Humanos , Polifenóis/farmacologia
13.
Phytother Res ; 30(2): 298-305, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26661587

RESUMO

Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption.


Assuntos
Anticarcinógenos/farmacologia , Neoplasias Colorretais/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Salvia officinalis/química , Chás de Ervas , Focos de Criptas Aberrantes/patologia , Animais , Azoximetano , Proliferação de Células/efeitos dos fármacos , Quimioprevenção , Citocromo P-450 CYP2E1/metabolismo , Feminino , Ratos , Ratos Endogâmicos F344
14.
Int J Infect Dis ; 38: 54-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26216762

RESUMO

OBJECTIVES: The clinical utility of sonication as an adjunctive diagnostic tool for the microbial diagnosis of cardiac implantable device-associated infections (CIDAIs) was investigated. METHODS: The implants of 83 subjects were investigated, 15 with a CIDAI and 68 without a clinical infection. Clinical data were analyzed prospectively and sonication fluid cultures (83 patients, 100%) and traditional cultures (31 patients, 37.4%) were performed RESULTS: Generator pocket infection and device-related endocarditis were found in 13 (86.7%) and four (26.7%) subjects, respectively. The mean numbers of previous technical complications and infections were higher in the infected patients compared to the non-infected patients (8 vs. 1, p<0.001; 2 vs. 0, p<0.031, respectively). The sensitivity and specificity for detecting CIDAI was 73.3% (11/15) and 48.5% (33/68) for sonication fluid culture, and 26.7% (4/15) and 100% (16/16) for traditional culture (p<0.001), respectively. A higher number of organisms were identified by sonication fluid than by tissue culture (58 vs. 4 specimens; p<0.001). The most frequent organisms cultured were Gram-positive cocci (66.1%), mainly coagulase-negative staphylococci (35.5%). Thirty-five (51.5%) non-infected subjects were considered colonized due to the positive identification of organisms exclusively through sonication fluid culture. CONCLUSIONS: Sonication fluid culture from the removed cardiac implants has the potential to improve the microbiological diagnosis of CIDAIs.


Assuntos
Desfibriladores Implantáveis/microbiologia , Endocardite Bacteriana/diagnóstico , Marca-Passo Artificial/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Sonicação , Adulto , Idoso , Idoso de 80 Anos ou mais , Endocardite Bacteriana/microbiologia , Feminino , Cocos Gram-Positivos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/microbiologia , Sensibilidade e Especificidade , Staphylococcus/isolamento & purificação
15.
Artigo em Inglês | MEDLINE | ID: mdl-26113868

RESUMO

Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme's in vitro activity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.

16.
Free Radic Biol Med ; 83: 262-72, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25744415

RESUMO

Mild stress-induced hormesis represents a promising strategy for targeting the age-related accumulation of molecular damage and, therefore, for preventing diseases and achieving healthy aging. Fruits, vegetables, and spices contain a wide variety of hormetic phytochemicals, which may explain the beneficial health effects associated with the consumption of these dietary components. In the present study, the induction of cellular antioxidant defenses by the phenolic diterpenes carnosic acid (CA) and carnosol (CS) were studied in normal human skin fibroblasts, and insights into the aging process at the cellular level investigated. We observed that CA and CS induced several cytoprotective enzymes and antioxidant defenses in human fibroblasts, whose induction was dependent on the cellular redox state for CS and associated with Nrf2 signaling for both compounds. The stress response elicited by preincubation with CS conferred a cytoprotective action against a following oxidant challenge with tert-butyl hydroperoxide, confirming its hormetic effect. Preincubation of normal fibroblasts with CS also protected against hydrogen peroxide-induced premature senescence. Furthermore, cultivation of middle passage normal human skin fibroblasts in the presence of CS ameliorated the physiological state of cells during replicative senescence. Our results support the view that mild stress-induced antioxidant defenses by CS can confer stress tolerance in normal cells and may have important implications in the promotion of healthy aging.


Assuntos
Abietanos/farmacologia , Antioxidantes/farmacologia , Senescência Celular/efeitos dos fármacos , Fibroblastos/citologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pele/citologia , Adulto , Apoptose/efeitos dos fármacos , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Técnicas Imunoenzimáticas , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/efeitos dos fármacos , Pele/metabolismo
17.
Eur J Pharm Sci ; 72: 34-45, 2015 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-25746954

RESUMO

In the present work, novel chromene derivatives fused with the imidazo[1,2-a]pyridine nucleus were tested for their anticancer potential in the human colorectal cancer HCT116 cells. Compounds 2a and 2c showed significant growth inhibitory activity with GI50 of 15 µM and 11 µM, respectively. Compound 2c, the most potent, has a carbamate group in position 8 of the pyridine ring, and showed significant cell cycle arrest and induction of cell death by apoptosis, even at 5 µM. Besides different potencies, chromene analogs 2a and 2c showed different mechanisms of action. Whereas the carbamate-free chromene 2a induced cell cycle arrest at G1/G0 phase, compound 2c showed to arrest cell cycle at both S and G2 phases. Chromene derivative 2a at concentrations higher than its GI50 remarkably induced caspases-dependent apoptosis in a p53-independent manner. On the other hand, compound 2c increased significantly p53 levels and induced apoptosis in a p53- and caspases-dependent manner, even at concentrations lower than its GI50. Both compounds increased the Bax/Bcl-2 ratio, induced mitochondria depolarization and activated MAP kinases. In conclusion, two novel and structurally similar chromene derivatives showed cytotoxicity to HCT16 cells through opposing effects on p53 levels and apoptosis mechanisms, which may be relevant for further development of drugs acting on distinct molecular targets useful in the treatment of cancers with different genetic profiles and for personalized medicine.


Assuntos
Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Neoplasias Colorretais/tratamento farmacológico , Dano ao DNA , Fibroblastos/efeitos dos fármacos , Células HCT116 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética
18.
Rev Bras Cir Cardiovasc ; 29(1): 31-6, 2014.
Artigo em Inglês, Português | MEDLINE | ID: mdl-24896160

RESUMO

INTRODUCTION: Chagas disease is a major cause of cardiomyopathy and sudden death in our country. It has a high mortality when their patients develop New York Heart Association (NYHA) class IV. OBJECTIVE: The objective of this study is to analyze the clinical outcome of patients with Chagas' cardiomyopathy with congestive heart failure with optimized pharmacological therapy, undergoing cardiac resynchronization therapy. METHODS: Between January 2004 and February 2009, 72 patients with Chagas' cardiomyopathy in NYHA class III and IV underwent cardiac resynchronization therapy and were monitored to assess their clinical evolution. We used the t test or the Wilcoxon test to compare the same variable in two different times. A P value < 0.05 was established as statistically significant. RESULTS: The average clinical follow-up was 46.6 months (range 4-79 months). At the end of the evaluation, 87.4% of patients were in NYHA class I or II (P<0.001). There was response to therapy in 65.3% of patients (P<0.001), with an overall mortality of 34.7%. CONCLUSION: In patients with chronic Chagas cardiomyopathy undergoing cardiac resynchronization therapy, we found the following statistically significant changes: improvement in NYHA class and increase of left ventricle ejection fraction, a decrease of the systolic final diameter and systolic final left ventricle volume and improvement of patient survival.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Chagásica/terapia , Insuficiência Cardíaca/terapia , Dispositivos de Terapia de Ressincronização Cardíaca , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Morte Súbita Cardíaca , Ecocardiografia Doppler , Eletrocardiografia , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
19.
Rev. bras. cir. cardiovasc ; 29(1): 31-36, Jan-Mar/2014. tab, graf
Artigo em Português | LILACS | ID: lil-710091

RESUMO

Introdução: A doença de Chagas é a maior causa de miocardiopatia e morte súbita em nosso país. Apresenta alta mortalidade quando seus portadores evoluem para classe funcional IV da New York Heart Association (NYHA). Objetivo: O objetivo deste trabalho é analisar a evolução clínica dos pacientes portadores de cardiomiopatia chagásica com insuficiência cardíaca avançada e terapia farmacológica otimizada submetido a terapia de ressincronização cardíaca. Métodos: Entre janeiro de 2004 e fevereiro de 2009, 72 pacientes com cardiomiopatia chagásica em classe funcional III e IV da NYHA foram submetidos à terapia de ressincronização cardíaca e acompanhados para avaliar sua evolução clínica. Para comparar a mesma variável em dois momentos diferentes utilizamos o Teste t pareado ou o Teste de Wilcoxon. Um valor de P<0,05 foi estabelecido como estatisticamente significante. Resultados: O acompanhamento clínico médio foi de 46,6 meses (variando de 4 a 79 meses). Ao final do seguimento, 87,4% dos pacientes estavam em classe funcional I ou II da NYHA (P<0,001). Houve resposta à terapia em 65,3% dos pacientes (P<0,001), com mortalidade total de 34,7%. Conclusão: Nos pacientes com cardiomiopatia chagásica crônica submetidos à terapia de ressincronização cardíaca, encontramos as seguintes alterações estatisticamente significativas: melhora da classe funcional segundo NYHA; melhora da fração de ejeção do ventrículo esquerdo; diminuição do diâmetro sistólico final e volume sistólico final do ventrículo esquerdo e maior sobrevida destes pacientes. .


Introduction: Chagas disease is a major cause of cardiomyopathy and sudden death in our country. It has a high mortality when their patients develop New York Heart Association (NYHA) class IV. Objective: The objective of this study is to analyze the clinical outcome of patients with Chagas' cardiomyopathy with congestive heart failure with optimized pharmacological therapy, undergoing cardiac resynchronization therapy. Methods: Between January 2004 and February 2009, 72 patients with Chagas' cardiomyopathy in NYHA class III and IV underwent cardiac resynchronization therapy and were monitored to assess their clinical evolution. We used the t test or the Wilcoxon test to compare the same variable in two different times. A P value < 0.05 was established as statistically significant. Results: The average clinical follow-up was 46.6 months (range 4-79 months). At the end of the evaluation, 87.4% of patients were in NYHA class I or II (P<0.001). There was response to therapy in 65.3% of patients (P<0.001), with an overall mortality of 34.7%. Conclusion: In patients with chronic Chagas cardiomyopathy undergoing cardiac resynchronization therapy, we found the following statistically significant changes: improvement in NYHA class and increase of left ventricle ejection fraction, a decrease of the systolic final diameter and systolic final left ventricle volume and improvement of patient survival. .


Assuntos
Humanos , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Chagásica/terapia , Insuficiência Cardíaca/terapia , Dispositivos de Terapia de Ressincronização Cardíaca , Doença Crônica , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Morte Súbita Cardíaca , Ecocardiografia Doppler , Eletrocardiografia , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
20.
RELAMPA, Rev. Lat.-Am. Marcapasso Arritm ; 26(4): 277-282, out.-dez. 2013. tab, graf
Artigo em Português | LILACS | ID: lil-716461

RESUMO

A síncope é um problema médico comum e, se relacionada a distúrbio da condução atrioventricular (AV), pode indicar o implante de marcapasso definitivo. Por isso, a distinção entre o bloqueio AV devido a doença degenerativa e aquele induzido por aumento do tônus vagal tem importante implicação prognóstica e terapêutica. O mecanismo responsável pela síncope vasovagal é a perda abrupta e transitória da consciência decorrente de hipoperfusão cerebral global e transitória, com início rápido, curta duração e recuperação completa e espontânea. É uma causa comum de síncope e tem bom prognóstico. Em sua forma cardioinibitória, costuma ter como mecanismo a bradicardia sinusal ou a assistolia associada a queda da pressão sanguínea, porém podem ocorrer outras apresentações menos comuns, como o bloqueio AV (BAVT, BAV 2:1 BAV avançado). Descreve-se o caso de uma paciente do sexo feminino, com 54 anos, hipertensa, chagásica (megaesôfago) e vários episódios de síncope no último ano. Foi investigada com eletrocardiograma (BAV 1º grau), ecocardiograma (normal), Holter (BAV 2 grau Mobitz I durante o sono), teste ergométrico (resposta cronotrópica e condução AV normais durante o esforço) e tilt test sensibilizado positivo (BAVT) com manutenção de distúrbios da condução atrioventricular (BAVT, BAV avançado) associados a pré-síncope após retorno a zero grau, quadro que durou 25 minutos. Como parte da investigação, foi submetida a estudo eletrofisiológico com intervalo HV normal. Foi indicado marcapasso definitivo, porém a paciente recusou-se. Retornou após um ano com manutenção do quadro de síncope. Foi então submetida a implante de marcapasso definitivo de dupla-câmara e encontra-se há 15 meses sem sintomas.


Syncope is a common medical problem and if related to disorder of atrioventricular (AV) conduction may be indicative of permanent pacemaker implantation. Therefore, the distinction between AV block due to degenerative disease and that induced by increased vagal tone has important prognostic and therapeutic implications. The mechanism responsible for vasovagal syncope is a sudden and transient loss of consciousness due to global cerebral hypoperfusion with rapid onset, short duration, and spontaneous complete recovery. It is a common cause of syncope and has a good prognosis. When cardioinhibitory, usually has as a mechanism of syncope sinus bradycardia or asystole associated to drop in blood pressure, but other less common presentations may occur as AV block (AVB, advanced AVB, AVB 2:1). We describe the case of a female patient, 54 years old, with hypertension, Chagas disease (megaesophagus) and several episodes of syncope in the last year. She was investigated by electrocardiogram (1st degree AVB), echocardiogram (normal), holter (Mobitz I 2nd degree AVB during sleep), exercise testing (normal chronotropic response and AV conduction during exercise) and tilt test (complete AVB) with maintenance of atrioventricular block (complete AVB and advanced AVB) associated with pre-syncope after returning to zero degree. This situation last for 25 minutes. As part of the investigation she underwent electrophysiologic study with normal HV interval. Permanent pacemaker was indicated but the patient refused. After 1 year she returned with maintenance of syncope and then underwent implantation of a permanent dual chamber pacemaker. She is without symptoms in the last 15 months.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Bloqueio Atrioventricular , Doença de Chagas/fisiopatologia , Marca-Passo Artificial , Síncope Vasovagal/etiologia , Taquicardia Ventricular/complicações , Taquicardia Ventricular/terapia
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