Navegando por Palavras-chave "Statin"
Agora exibindo 1 - 9 de 9
Resultados por página
Opções de Ordenação
- ItemAcesso aberto (Open Access)Análises morfofuncionais, bioquímicas e moleculares de modelo experimental de miopatia associada à estatina(Universidade Federal de São Paulo (UNIFESP), 2017-03-06) Andrade, Pamela Vieira de [UNIFESP]; Silva, Helga Cristina Almeida da [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; http://lattes.cnpq.br/7917312029683516; http://lattes.cnpq.br/0844918862241102; http://lattes.cnpq.br/3536599065009604; Universidade Federal de São Paulo (UNIFESP)Introdução: As estatinas atualmente são consideradas os agentes mais úteis para o tratamento da hipercolesterolemia. Nos últimos anos, aumentaram os relatos sobre efeitos colaterais importantes no músculo esquelético, com mialgia, aumento dos valores séricos de creatinoquinase (CK) e até rabdomiólise após uso de altas doses dessas medicações. O reconhecimento precoce da miopatia induzida pelas estatinas e a descontinuação das estatinas é fundamental na prevenção da miopatia e diminuição de possíveis sequelas. Objetivos: 1. Estudar o efeito da estatina sobre a contração e contratura muscular em ratos expostos a baixas e altas concentrações da sinvastatina 2. Correlacionar essas alterações com a morfologia, bioquímica e proteômica da fibra muscular e 3. Analisar o uso do bloqueador de canal de liberação de cálcio (dantrolene) no presente modelo. Material e Métodos: O estudo foi realizado com 50 ratos machos Wistar, divididos em 5 grupos: A - Controle; B - Estatina baixa dose (5 mg/kg/dia); C - Estatina alta dose (20 mg/kg/dia); D – Sem estatina, com dantrolene (5 mg/Kg); E – Estatina alta dose (20 mg/kg/dia) e dantrolene (5 mg/Kg). Os animais dos grupos B, C e E receberam a sinvastatina diariamente, diluída com carboximetilcelulose (CMC) 0,5%, via gavagem, por dois meses; os do grupo A e D receberam apenas o veículo (CMC), via gavagem, por dois meses; os dos grupos D e E receberam ainda dantrolene (5 mg/Kg) via subcutânea por dois meses. Os animais foram pesados semanalmente, sendo anotado o consumo da dieta líquida e sólida diariamente; a cada sete dias foram realizados exames físico e neurológico. Após dois meses, os animais foram anestesiados para a retirada dos músculos vastos laterais, gastrocnêmios e sóleos. Com os vastos laterais foram realizados testes de estimulação elétrica in vitro em presença de halotano e cafeína - nos quais as curvas de contração e contratura de cada teste foram analisadas - e teste de estimulação tetânica pré e pós-isquemia - referido como grau de contração após cada estímulo elétrico. Com os gastrocnêmios e os sóleos foi realizado estudo morfológico (histologia e morfometria). O gastrocnêmio foi empregado ainda para estudo bioquímico, feito pela quantificação do malonaldeído (MDA), e análise proteômica por espectrometria de massas. Resultados: Na estimulação elétrica in vitro na presença de cafeína, houve aumento significativo nos valores de contração nas concentrações de 1; 1,5; 2; 3, 4 e 32 mM de cafeína do grupo C em relação aos outros grupos. Não houve diferença significativa da contração em resposta a diferentes concentrações de halotano e a diferentes estimulações tetânicas pré e pós-isquemia, bem como não houve diferença no grau de contratura após vários estímulos. Houve aumento significativo na produção de MDA no grupo C em relação ao grupo B. O estudo morfológico qualitativo mostrou, na reação do Tricrômico de Gomori, pequenos aglomerados fucsinofílicos grosseiros na periferia das fibras musculares, vistos mais uniformemente no grupo C. Na análise morfométrica do músculo gastrocnêmio, pela coloração de hematoxilina/eosina, houve diminuição significante da área transversa das fibras musculares no grupo C em relação aos grupos D e E. Na análise proteômica houve aumento significativo da expressão das proteínas glicolíticas nos grupos tratados com estatina. Conclusão: Nossos dados mostraram que, apesar dos animais não apresentarem miopatia clínica evidente, doses de estatina de 20 mg/Kg/dia aumentaram a contração muscular após estímulo com cafeína, provocaram alterações morfológicas mitocondriais com atrofia do músculo gastrocnêmio e aumentaram a peroxidação lipídica no músculo.
- ItemAcesso aberto (Open Access)Avaliação da expressão proteica e de elementos em plasma sanguíneo após o uso de estatinas em pacientes infartados(Universidade Federal de São Paulo, 2022-10-04) Araujo, Isabela Carvalho Lobo de [UNIFESP]; Lopes, Aline Soriano [UNIFESP]; Klassen, Aline [UNIFESP]; http://lattes.cnpq.br/5905235296066398; http://lattes.cnpq.br/0894290130191292; http://lattes.cnpq.br/1457262065934541Estudos a nível molecular envolvendo pacientes que sofreram infarto agudo do miocárdio fornecem uma nova visão sobre o conhecimento da expressão clínica e patológica da doença. Atualmente, avanços tecnológicos nas plataformas conhecidas com a terminologia “ômicas” permitem a avaliação de mudanças sistemáticas em diversos sistemas biológicos e tem sido aplicada extensivamente a doenças cardiovasculares. O sangue está em contato direto e constante com o sistema cardíaco, fazendo do plasma o fluido mais adequado para o estudo dos componentes advindos de uma oclusão coronária, que é o caso do infarto. Além das proteínas, o plasma possui diversas outras moléculas biológicas interessantes, tais como macro e micronutrientes elementares. A avaliação do perfil proteico por meio da proteômica tem auxiliado na compreensão da evolução de doenças e estratégias terapêuticas. Ainda, sabe-se que há interação entre diversos elementos químicos com proteínas e essa interação pode ser modificada devido a algum distúrbio biológico como uma doença ou uso de fármacos. Logo, o estudo dos íons elementares em conjunto com as proteínas pode aumentar as informações sobre as doenças cardiovasculares, além de ampliar o conhecimento sobre a ação de fármacos no organismo. Dentro deste cenário, o objetivo desse estudo foi avaliar a expressão proteica diferencial em pacientes infartados e tratados com duas estatinas diferentes, bem como explorar possíveis alterações de elementos essenciais na evolução desses pacientes, e corroborar os resultados oriundos dos dois estudos. Um total de 199 proteínas foram identificadas; entre as quais, 11 proteínas foram expressas de forma significativa entre os grupos de pacientes estudados. Algumas proteínas estão relacionadas a processos de agregação plaquetária, tais como o fibrinogênio e a hemoglobina; enquanto outras exercem a função de associação de íons cálcio, tais como a Proteína C reativa, subcomponente do Complemento C1s e Paraoxonase / arilesterase 1 sérica. Pela análise de agrupamento hierárquico observou-se que o perfil proteico é mais diferentemente expresso com relação ao tempo de administração da droga do que o tipo de estatina usada no tratamento do infarto. O mesmo comportamento foi observado na análise de PCSK9, em que maiores concentrações foram encontradas em decorrência do tempo de tratamento. Entre os íons elementares analisados, apenas o cobre apresentou variação significativa entre as visitas. A redução nos níveis de cobre no plasma, pode estar relacionada com o aumento de expressão da proteína Paraoxonase 1 sérica.
- ItemSomente MetadadadosComparação De Diferentes Protocolos Na Estratificação Do Risco Cardiovascular E Indicação Do Uso De Estatina Em Pacientes Portadores De Hipertensão Arterial(Universidade Federal de São Paulo (UNIFESP), 2018-05-25) Oliveira, Vinicius De [UNIFESP]; Batista, Marcelo Costa [UNIFESP]Objective: To Evaluate The Difference In Indication Of The Use Of Statin In Patients Submitted To Different Protocols Of Stratification Of Cardiovascular Risk For The Treatment Of Dyslipidemia. Methods: A Total Of 641 Patient Charts Were Reviewed Regularly In The Osvaldo Ramos Foundation Hypertension Outpatient Clinic, Who Were Without The Use Of Statin. These Patients Were Submitted To The Application Of Different Guidelines To Classify The Cardiovascular Risk. The Framingham And Pooled Cohort Equation Scores Were Used. After These Patients Were Submitted To Different Protocols For Calculating Cardiovascular Risk, The Criteria Were Applied According To Each National Cholesterol Education Program's Adult Treatment Panel Iii And American College Of Cardiology/American Heart Association 2013 Protocol For The Start Of The Use Of Statins. Results: Of The 641 Patients Analyzed (56.9 ± 9.7 Years, 66.1% Female, 30.7% Diabetic, 31% Black, 11.2% Smoker, 44.1% With Metabolic Syndrome, 10 (33%) Were Identified As Having
- ItemAcesso aberto (Open Access)Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies(Associação Brasileira de Divulgação Científica, 2012-11-01) Kasmas, Soraia Hani [UNIFESP]; Izar, Maria Cristina de Oliveira [UNIFESP]; França, Carolina Nunes [UNIFESP]; Ramos, Silvia Cristina [UNIFESP]; Moreira, Flávio Tocci [UNIFESP]; Helfenstein, Tatiana [UNIFESP]; Moreno, Ronilson Agnaldo; Borges, Ney Carter do Carmo; Figueiredo Neto, Antonio Martins; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Instituto Nacional de Ciência e Tecnologia de Fluidos Complexos; SynchropharEffective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.
- ItemAcesso aberto (Open Access)Efeito da estatina sobre a densidade óssea avaliada pela tomografia computadorizada vertebral em receptores de transplante renal(Universidade Federal de São Paulo (UNIFESP), 2019-08-02) Sa, Cinara Barros De [UNIFESP]; Carvalho, Aluizio Barbosa De [UNIFESP]; Canziani, Maria Eugênia Fernandes [UNIFESP]; http://lattes.cnpq.br/8616590420890318; http://lattes.cnpq.br/7909431111187945; http://lattes.cnpq.br/5353063932221435; Universidade Federal de São Paulo (UNIFESP)Bone disease after successful kidney transplantation is common and represents an association of pre-existing renal osteodystrophy, the reduced renal function after renal transplantation and the consequences of transplantation specific therapies on bone. Statins are widely prescribed drugs for the treatment of dyslipidemia that have a wide range of pleiotropic effects including a possible positive effect on bone metabolism. One hundred and seventeen patients incidents in kidney transplant were randomized to receive statin or not during 12 months. Clinical evaluation, laboratorial analysis and chest-computed tomography were performed within 1 and 2 months after kidney transplantation and with 12-month follow-up. The thoracic vertebra was used to the vertebral bone density measurement. At baseline, statin group had higher BMI, total cholesterol, LDL cholesterol, triglycerides levels and malnutrition frequency than control group. At the end of follow up period, there was no significant difference in the clinical or laboratorial parameters between groups. There was no difference in vertebral bone density comparing statin and control groups neither in univariate or multivariate analysis. The main explanations for our result are the complexity of bone disease in kidney transplant recipients and the way statins were administered, probably inadequate to achieve an effective bone concentration.
- ItemSomente MetadadadosEndothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease(Japanese Circulation Soc, 2012-03-01) Franca, Carolina N. [UNIFESP]; Pinheiro, Luiz F. M. [UNIFESP]; Izar, Maria C. O. [UNIFESP]; Brunialti, Milena K. C. [UNIFESP]; Salomao, Reinaldo [UNIFESP]; Bianco, Henrique T. [UNIFESP]; Kasmas, Soraia H. [UNIFESP]; Barbosa, Simone P. [UNIFESP]; Nucci, Gilberto de; Fonseca, Francisco A. H. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Natl Inst Complex Fluids; Universidade Estadual de Campinas (UNICAMP)Background: Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. the aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC).Methods and Results: A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80 mg, visits 1-3; clopidogrel 75 mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24 h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C-max], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC(last)], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C-max, P=0.009; AUC(last), P=0.039). PMP were inversely correlated with clopidogrel C. on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC(last) on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). in addition, clopidogrel C-max was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found.Conclusions: the balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease. (Circ J 2012; 76: 729-736)
- ItemSomente MetadadadosEstudo Da Ação Dos Inibidores Da 3-Hidroximetilglutaril Coa Redutase Sobre A Secreção De Citocinas Inflamatórias Em Células Endoteliais Estimuladas Com Soro Urêmico(Universidade Federal de São Paulo (UNIFESP), 2017-06-29) Carmona, Silmara De Melo [UNIFESP]; Batista, Marcelo Costa [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Atherosclerosis, the anatomopathological basis of dyslipidemia, is associated with the occurrence of cardiovascular diseases (CVD), demonstrating a high prevalence in chronic renal disease (CKD). Non-traditional risk factors such as the uremic environment and inflammation promote metabolic alterations related with CVD. Uremic mileu has been considered preponderant issue for secretion of cytokines, as TNF-α and interleukins, which are associated with endothelial dysfunction. Statins, drugs that inhibit the enzyme 3-Hydroxymethylglutaryl CoA Reductase, preventing the formation of mevalonic acid and its precursors, have pleiotropic effects with potential benefit under such conditions of systemic inflammatory response. Objective: The aim of the present study was to characterize immortalized human umbilical vein cells by expressing constitutive and specific markers, as well as analyzing the impact of simvastatin on the secretion of TNF-α and IL-10 in endothelial cells stimulated with uremic serum. Methods: To validated the source of the cell line used as in vitro model in this study, cell culture was incubated with primary monoclonal antibodies and secondary antibodies conjugated to Allophycocyanin (APC) and Phycoerythrin (PE). After, the cells were submitted to flow cytometry and immunofluorescence methods to evaluate the expression of constitutive and specific markers. For the study of the impact of 3-Hydroxymethylglutaryl CoA reductase inhibitors on the expression and secretion of IL-10 and TNF-α, HUVEC cells were pretreated with simvastatin and insulted with uremic serum and serum from healthy subjects. Additionally, the cell supernatant was collected and analyzed by ELISA method. Results and Conclusions: Our findings confirm the endothelial origin of the cells used in this study by which expressing the constitutive markers CD31, CD146 and vWF, as well as the expression of the specific markers VCAM and ICAM in the cells incubated with TNF-α, mimicking the inflammatory scenario. We also demonstrate that 3-Hydroxymethylglutaryl CoA reductase inhibitors have a pleiotropic effect on endothelial tissue, reducing TNF-α secretion and increasing IL-10 secretion. These actions determine the partial reversal of the inflammatory response and consequently, the attenuation of endothelial dysfunction which is observed in the uremic environment. However, the elucidation of the mechanisms by which statins acts in the endothelium should be the object of future studies.
- ItemAcesso aberto (Open Access)Estudo da associação da vitamina D e do inibidor da 3- hidroximetilglutaril coa redutase na função endotelial em portadores de hipertensão arterial: um estudo duplo-cego, placebo-controlado(Universidade Federal de São Paulo (UNIFESP), 2020-01-30) Kohatsu, Anderson Simabuco [UNIFESP]; Batista, Marcelo Costa [UNIFESP]; http://lattes.cnpq.br/0614350233628814; http://lattes.cnpq.br/6572506670639242; Universidade Federal de São PauloHypertension is considered a substantial trouble in public health. Because it is an easily diagnosed disease, but difficult to control and follow up, it needs special attention especially due to its association with cardiovascular outcomes and the great impact on morbidity and mortality of the population. The biological vulnerability of an inflammatory vascular environment can lead to impaired vascular regulation linked to a process of endothelial dysfunction and, consequently, a higher risk of developing hypertension. In this scenario, there is growing evidence of the benefits of Vitamin D and the 3- Hydroxymethylglutaryl CoA Reductase Inhibitor (Statin) in reducing inflammation and improving endothelial function through pleiotropic effects. However, the number of intervention studies is limited and raises questions about causal relationship, long-term interaction and benefits of these drugs in blood pressure control. The present double-blind, placebo-controlled study using a 2x2 factorial design proposals to evaluate the effect of the association between Vitamin D and Statin, compared with their respective placebos, on blood pressure, mensuration of dimethyl arginine-asymmetric endothelial function (ADMA) and inflammatory profile in patients with hypertension. Sixty eligible subjects were randomized to 4 groups of 15 patients at a 1: 1: 1: 1 ratio to receive simvastatin 40mg/day or vitamin D 200,000Ui starting dose followed by 100,000Ui/month (4 doses) alone or simvastatin with vitamin D or placebos treatment over 22 weeks. Throughout the period, monthly consultations were performed with monitoring of clinical parameters including blood pressure and antihypertensive adjustments in a stepwise manner according to protocol. Additionally before the intervention and at the end of the study, blood pressure was also measured by ambulatory blood pressure monitoring (ABPM) and laboratory tests including serum ADMA and C-reactive protein measurements from all participants. The results obtained with the intervention did not determine changes in systemic blood pressure levels at the end of follow-up, either by ABPM or office blood pressure, nor did it change the values of asymmetric dimethylarginine and C-reactive protein. Thus, we demonstrated that vitamin D supplementation and simvastatin treatment, alone or in combination, over 22 weeks in hypertensive patients with low cardiovascular risk did not lead to a reduction in blood pressure or changes in variables related to endothelial function and inflammation.
- ItemSomente MetadadadosMicropartículas e doença cardiovascular hipertensiva: efeitos do tratamento anti-hipertensivo e hipolipemiante em micropartículas circulantes(Universidade Federal de São Paulo (UNIFESP), 2018-04-26) Massunaga, Nayara Dantas [UNIFESP]; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; França, Carolina Nunes; http://lattes.cnpq.br/6580677601405775; http://lattes.cnpq.br/2393476657163442; http://lattes.cnpq.br/1470279541149956; Universidade Federal de São Paulo (UNIFESP)Introduction: Patients with hypertension on stage 2 are usually treated with a combination of two antihypertensive drugs. However, the combination including a diuretic or a calcium channel blocker may determine different effects on vessels, despite similar decrease on blood pressure. Objectives: This study aimed to compare the effects of amlodipinebased treatment with that obtained by hydrochlorothiazide monotherapy or sequentially combined with valsartan and addition and subsequent withdrawal of rosuvastatin on circulating microparticles. An exploratory analysis was also performed on the effects on central blood pressure parameters and vascular compliance. Methods: Prospective, randomized, openlabel with blinded outcomes study included patients of both sexes on stage 2 hypertension who remained for four weeks on the use of amlodipine (n = 24) or hydrochlorothiazide (n = 22) monotherapy. At the end of this period, blood samples were collected for protocol analyses and blood pressure data were obtained. Three sequential fourweek periods were followed at the end of which the mentioned laboratory and blood pressure parameters were obtained. In the second period valsartan 160 mg was added in both arms of the study, in the third rosuvastatin 20 mg and in the last rosuvastatin was suspended, and the antihypertensive treatment was maintained for four weeks. Monocytic, endothelial and platelet microparticles were quantified by flow cytometry and specific antibodies at the end of each intervention period. Results: Biochemical parameters and peripheral blood pressure were similar between the two groups at the end of treatment as monotherapy, as well as throughout the study. However, central pressure parameters were lower in the anlodipine arm from the addition of valsartan (p = 0.002) and did not change in the hydrochlorothiazide arm. The pulse wave velocity was not changed in both treatment groups. Circulating monocytic microparticles remained unchanged in the amlodipine group, but increased in the hydrochlorothiazide group (p = 0.02). For the circulating endothelial microparticles, a reduction with the hydrochlorothiazide group was observed throughout the study. With regard to circulating platelet microparticles, a greater amount was observed after suspension of rosuvastatin in the anlodipine arm. Conclusions: The choice of combination treatment based on amlodipine or hydrochlorothiazide has different effects on both circulating microparticles and synergism with other drugs. In addition, they show important differences in central hemodynamic parameters. These findings suggest differences in cardiovascular protection.