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1.
Artigo em Inglês | MEDLINE | ID: mdl-31701487

RESUMO

Leishmaniasis occurs in the five continents and represents a serious public health challenge, but is still a neglected disease, and the current pharmacological weaponry is far from satisfactory. Triglyceride-rich nanoparticles mimicking chylomicrons (TGNP) behave metabolically like native chylomicrons when injected into the bloodstream. Previously we have shown that TGNP as vehicle to amphothericin B (AB) for treatment of fungi infection showed reduced renal toxicity and lower animal death rates compared to conventional AB. The aim of the current study was to test the tolerability and effectiveness of the TGNP-AB preparation in a murine model of Leishmania amazonensis infection. The in vitro assays determined the cytotoxicity of TGNP-AB, AB, and TGNP in macrophages and promastigote forms and the leishmanicidal activity in infected macrophages. The in vivo toxicity tests were performed in healthy mice with increasing doses of TGPN-AB and AB. Then, animals were treated with 2.5 mg/kg/day of AB, 17.5 mg/kg/day of TGNP-AB, or TGNP three times a week for 4 weeks. TGNP-AB formulation was less cytotoxic for macrophages than AB. TGNP-AB was more effective than AB against the promastigotes forms of the parasite and more effective in reducing the number of infected macrophages and the number of amastigotes forms per cell. TGNP-AB-treated animals showed lower hepatotoxicity. In addition, TGNP-AB group showed a marked reduction in lesion size on the paws and parasitic load. The TGNP-AB preparation attained excellent leishmanicidal activity with remarkable lower drug toxicity at very high doses that, due to the toxicity-buffering properties of the nanocarrier, become fully tolerable.

2.
In. Negrão, Carlos Eduardo; Pereira-Barretto, Antônio Carlos; Rondon, Maria Urbana Pinto Brandão. Cardiologia do exercício: do atleta ao cardiopata / Exercise cardiology: from athlete to heart disease. São Paulo, Manole, 4ª; 2019. p.86-125.
Monografia em Português | LILACS | ID: biblio-1015360
3.
Clinics (Sao Paulo) ; 73: e189, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30365817

RESUMO

OBJECTIVES: To evaluate biomarkers associated with early cardiometabolic risk in obese adolescents. METHODS: This cross-sectional study included 137 adolescents of both sexes aged 10 to 19 years divided into a normal weight group (NW) (n=69) and an obese group (OB) (n=68). RESULTS: As expected, obesity showed positive associations with homeostatic model assessment for insulin resistance (HOMA-IR), triacylglycerol, insulin, plasma levels of non-esterified fatty acids, and cholesterol ester transfer protein activity and negative associations with plasma antioxidant levels. Plasma oxidized low-density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL(-)] levels were significantly higher in the OB group. Higher tertiles of oxLDL were associated with increased values of body mass index; waist circumference; fatty mass percentage (%FM); and the atherogenic lipids non-high-density-lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and triacylglycerol. Higher tertiles of LDL(-) were robustly associated with body mass index and waist circumference. Logistic regression models (odds ratios) confirmed that increased values of lipids and apolipoprotein B were associated with increased risk of oxLDL. For LDL(-), these associations were not significant, suggesting that another mechanism is involved in generating this particle in obese adolescents. CONCLUSIONS: Obese adolescents showed increased plasma LDL(-) and oxLDL, and obese girls had more LDL(-) than obese boys. Therefore, oxLDL is strongly and independently associated with classical cardiovascular risk factors, while increased levels of LDL(-) were influenced by body mass index, waist circumference and demographic parameters in obese adolescents.


Assuntos
Doenças Cardiovasculares/sangue , Lipoproteínas LDL/sangue , Obesidade/sangue , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/complicações , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
4.
Clin Nutr ; 37(2): 618-623, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28249700

RESUMO

The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food.


Assuntos
Apolipoproteínas/sangue , Ésteres do Colesterol/sangue , Euterpe/metabolismo , Lipoproteínas HDL/sangue , Extratos Vegetais/farmacologia , Adulto , Apolipoproteínas/efeitos dos fármacos , Biomarcadores/sangue , Dieta/métodos , Feminino , Frutas/metabolismo , Humanos , Lipídeos/sangue , Lipoproteínas HDL/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/metabolismo , Estudos Prospectivos , Valores de Referência , Adulto Jovem
5.
Clinics ; 73: e189, 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-974943

RESUMO

OBJECTIVES: To evaluate biomarkers associated with early cardiometabolic risk in obese adolescents. METHODS: This cross-sectional study included 137 adolescents of both sexes aged 10 to 19 years divided into a normal weight group (NW) (n=69) and an obese group (OB) (n=68). RESULTS: As expected, obesity showed positive associations with homeostatic model assessment for insulin resistance (HOMA-IR), triacylglycerol, insulin, plasma levels of non-esterified fatty acids, and cholesterol ester transfer protein activity and negative associations with plasma antioxidant levels. Plasma oxidized low-density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL(-)] levels were significantly higher in the OB group. Higher tertiles of oxLDL were associated with increased values of body mass index; waist circumference; fatty mass percentage (%FM); and the atherogenic lipids non-high-density-lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and triacylglycerol. Higher tertiles of LDL(-) were robustly associated with body mass index and waist circumference. Logistic regression models (odds ratios) confirmed that increased values of lipids and apolipoprotein B were associated with increased risk of oxLDL. For LDL(-), these associations were not significant, suggesting that another mechanism is involved in generating this particle in obese adolescents. CONCLUSIONS: Obese adolescents showed increased plasma LDL(-) and oxLDL, and obese girls had more LDL(-) than obese boys. Therefore, oxLDL is strongly and independently associated with classical cardiovascular risk factors, while increased levels of LDL(-) were influenced by body mass index, waist circumference and demographic parameters in obese adolescents.

6.
Faludi, André Arpad; Izar, Maria Cristina de Oliveira; Saraiva, José Francisco Kerr; Chacra, Ana Paula Marte; Bianco, Henrique Tria; Afiune Neto, Abrahão; Bertolami, Adriana; Pereira, Alexandre C.; Lottenberg, Ana Maria; Sposito, Andrei C.; Chagas, Antonio Carlos Palandri; Casella Filho, Antonio; Simão, Antônio Felipe; Alencar Filho, Aristóteles Comte de; Caramelli, Bruno; Magalhães, Carlos Costa; Negrão, Carlos Eduardo; Ferreira, Carlos Eduardo dos Santos; Scherr, Carlos; Feio, Claudine Maria Alves; Kovacs, Cristiane; Araújo, Daniel Branco de; Magnoni, Daniel; Calderaro, Daniela; Gualandro, Danielle Menosi; Mello Junior, Edgard Pessoa de; Alexandre, Elizabeth Regina Giunco; Sato, Emília Inoue; Moriguchi, Emilio Hideyuki; Rached, Fabiana Hanna; Santos, Fábio César dos; Cesena, Fernando Henpin Yue; Fonseca, Francisco Antonio Helfenstein; Fonseca, Henrique Andrade Rodrigues da; Xavier, Hermes Toros; Mota, Isabela Cardoso Pimentel; Giuliano, Isabela de Carlos Back; Issa, Jaqueline Scholz; Diament, Jayme; Pesquero, João Bosco; Santos, José Ernesto dos; Faria Neto, José Rocha; Melo Filho, José Xavier de; Kato, Juliana Tieko; Torres, Kerginaldo Paulo; Bertolami, Marcelo Chiara; Assad, Marcelo Heitor Vieira; Miname, Márcio Hiroshi; Scartezini, Marileia; Forti, Neusa Assumpta; Coelho, Otávio Rizzi; Maranhão, Raul Cavalcante; Santos Filho, Raul Dias dos; Alves, Renato Jorge; Cassani, Roberta Lara; Betti, Roberto Tadeu Barcellos; Carvalho, Tales de; Martinez, Tânia Leme da Rocha; Giraldez, Viviane Zorzanelli Rocha; Salgado Filho, Wilson.
Arq. bras. cardiol ; 109(2,supl.1): 1-76, ago. 2017. tab, graf
Artigo em Português | LILACS-Express | ID: biblio-887919
7.
Int J Nanomedicine ; 12: 3827-3837, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28572727

RESUMO

Lipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m2) and three with higher (250 mg/m2) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight-food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents.


Assuntos
Antineoplásicos/efeitos adversos , Lipídeos/química , Nanopartículas/efeitos adversos , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Cebus , Colesterol/química , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/farmacologia , Emulsões/administração & dosagem , Emulsões/química , Masculino , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Distribuição Tecidual , Testes de Toxicidade Crônica/métodos
8.
Lipids ; 52(8): 703-709, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28660528

RESUMO

Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1ß, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.


Assuntos
Apolipoproteína A-I/análise , Biomarcadores/sangue , HDL-Colesterol/sangue , Inflamação/metabolismo , Lipoproteínas LDL/análise , Adulto , Apolipoproteína A-I/sangue , Pessoas Acamadas , Ésteres do Colesterol , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Lipídeos/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/sangue , Comportamento Sedentário
9.
Clinics (Sao Paulo) ; 71(3): 163-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27074178

RESUMO

OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which seemed to be related to the presence of PPAR-α.


Assuntos
Infarto do Miocárdio/metabolismo , PPAR alfa/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Apoptose/fisiologia , Feminino , Inflamação/metabolismo , Modelos Animais , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , NF-kappa B/metabolismo , PPAR alfa/análise , Distribuição Aleatória , Ratos Wistar , Tempo , Fator de Necrose Tumoral alfa/metabolismo , Ultrassonografia , Função Ventricular/fisiologia
10.
Clinics ; 71(3): 163-168, Mar. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-778995

RESUMO

OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which seemed to be related to the presence of PPAR-α.


Assuntos
Animais , Feminino , Infarto do Miocárdio/metabolismo , PPAR alfa/metabolismo , Condicionamento Físico Animal/fisiologia , Apoptose/fisiologia , Inflamação/metabolismo , Modelos Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio , NF-kappa B/metabolismo , PPAR alfa/análise , Distribuição Aleatória , Ratos Wistar , Tempo , Fator de Necrose Tumoral alfa/metabolismo , Função Ventricular/fisiologia
11.
BMC Cardiovasc Disord ; 15: 72, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26195004

RESUMO

BACKGROUND: Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries. METHODS: We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined. RESULTS: Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10-16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance. CONCLUSION: Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population. TRIAL REGISTRATION: http://www.controlled-trials.com REGISTRATION NUMBER: ISRCTN26970041.


Assuntos
Doença da Artéria Coronariana/sangue , Diabetes Mellitus Tipo 2/sangue , Troponina C/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Oxirredução , Peroxidase/sangue , Fatores de Risco , Tirosina/análogos & derivados , Tirosina/sangue
12.
Arq Bras Cardiol ; 103(1): 76-84, 2014 Jul.
Artigo em Inglês, Português | MEDLINE | ID: mdl-25120086

RESUMO

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.


Assuntos
Lipoproteína(a)/fisiologia , Apolipoproteínas A/química , Apolipoproteínas A/genética , Humanos , Lipoproteína(a)/análise , Lipoproteína(a)/metabolismo , Fatores de Risco
13.
Arq. bras. cardiol ; 103(1): 76-84, 07/2014. tab
Artigo em Inglês | LILACS | ID: lil-718102

RESUMO

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.


A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.


Assuntos
Humanos , Lipoproteína(a)/fisiologia , Apolipoproteínas A/química , Apolipoproteínas A/genética , Lipoproteína(a)/análise , Lipoproteína(a)/metabolismo , Fatores de Risco
14.
Dis Markers ; 2014: 480201, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24719500

RESUMO

BACKGROUND: Paraoxonase-1 (PON1) activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1). We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART). METHODS: PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve), and 509 were receiving HAART). HIV-1 infected individuals were treated with the following: efavirenz (EFV; n = 195) or nevirapine (NVP; n = 95) or lopinavir/ritonavir (LOP/r; n = 219). Serum levels of total cholesterol (TC), HDL, and low-density lipoprotein (LDL) fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios) were determined. RESULTS: PON1 activity (U/L) was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r = 0,121; P = 0,014). The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio) in comparison with other groups. CONCLUSION: PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.


Assuntos
Fármacos Anti-HIV/farmacologia , Arildialquilfosfatase/sangue , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por HIV/enzimologia , HIV-1/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Arq. bras. cardiol ; 100(5): 404-411, maio 2013. ilus, tab
Artigo em Português | LILACS | ID: lil-675601

RESUMO

FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina), fatores do metabolismo glicídico [hemoglobina glicada (HbA1c), insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina), glicerídeos (triglicérides, VLDL e ácido graxo), fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1), inflamação (proteína C reativa ultrassensível) e necrose miocárdica (CK-MB e troponina). Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p < 0,001), lipoproteínas (p = 0,03) e fatores de necrose (p = 0,03). Na análise multivariada, somente metabolismo glicídico (OR = 4,3; IC = 2,1-68,9 e p < 0,001) e necrose miocárdica (OR = 22,5; IC = 2-253 e p = 0,012) mantiveram correlação independente e significativa.Para análise da influência da história de diabetes mellitus , modelo de regressão, incluindo somente pacientes sem diabetes mellitus foi desenvolvido, e os resultados não alteraram. Finalmente, no modelo ajustado para idade, sexo e variáveis clínicas(história de diabetes mellitus, hipertensão arterial e dislipidemia), três variáveis mantiveram associação significativa e independente com hiperglicemia: metabolismo glicídico (OR = 24,1; IC = 4,8-122,1 e p < 0,001) necrose miocárdica (OR = 21,9; IC = 1,3-360,9 e p = 0,03) e história de DM (OR = 27, IC = 3,7-195,7 e p = 0,001). CONCLUSÃO: Marcadores do metabolismo glicídico e necrose miocárdica foram os melhores preditores de hiperglicemia em pacientes com infarto agudo do miocárdio.


BACKGROUND: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic. RESULTS: Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001). CONCLUSION: Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus/diagnóstico , Hiperglicemia/diagnóstico , Infarto do Miocárdio/sangue , Troponina/sangue , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Creatina Quinase Forma MB/sangue , Diabetes Mellitus/sangue , Métodos Epidemiológicos , Hemoglobina A Glicada/análise , Hiperglicemia/sangue , Inflamação/sangue , Insulina/sangue , Lipoproteínas/sangue , Infarto do Miocárdio/patologia , Necrose , Estresse Fisiológico/fisiologia
16.
Arq Bras Cardiol ; 100(5): 404-11, 2013 May.
Artigo em Inglês, Português | MEDLINE | ID: mdl-23598457

RESUMO

BACKGROUND: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic. RESULTS: Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001). CONCLUSION: Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.


Assuntos
Diabetes Mellitus/diagnóstico , Hiperglicemia/diagnóstico , Infarto do Miocárdio/sangue , Troponina/sangue , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Creatina Quinase Forma MB/sangue , Diabetes Mellitus/sangue , Métodos Epidemiológicos , Feminino , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/sangue , Inflamação/sangue , Insulina/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Necrose , Estresse Fisiológico/fisiologia
17.
J Cardiovasc Pharmacol ; 59(4): 308-14, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22113347

RESUMO

A decrease in the number of cardiovascular events in patients with rheumatoid arthritis or psoriasis treated with methotrexate (MTX) has been observed in the literature. The aim of this study was to test whether MTX could promote anti-inflammatory effects and reduce the atherosclerotic lesions in rabbits with atherosclerosis induced by cholesterol feeding. Twenty male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 of cholesterol feeding, 10 animals were treated with 4 weekly intravenous injections of MTX (4 mg/kg) and 10 with 4 weekly saline solution injections for 30 days. MTX reduced the size of the lesion areas of cholesterol-fed animals by 75% and intima-media ratio 2-fold. The drug inhibited macrophage migration into the intima by 50% and the presence of apoptotic cells by 84% but did not inhibit the intimal proliferation of smooth muscle cells. MTX treatment also diminished the positive staining area of metalloproteinase 9 in the intima, which is probably beneficial. In the tumor necrosis factor-α-treated human umbilical vein endothelial cell line, incubation with MTX led to downregulation of 5 pro-inflammatory genes, TNF-α, VAP-1, IL-1ß, CXCL2, and TLR2, and upregulation of the anti-inflammatory TGF-ß1 gene, thus showing endothelium-protective properties. In conclusion, MTX showed direct in vivo anti-atherosclerotic action and may have potential in the treatment of this disorder.


Assuntos
Anti-Inflamatórios/farmacologia , Aterosclerose/prevenção & controle , Colesterol na Dieta/toxicidade , Metotrexato/farmacologia , Animais , Apoptose , Aterosclerose/etiologia , Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Macrófagos/metabolismo , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Coelhos , Fator de Necrose Tumoral alfa/administração & dosagem , Regulação para Cima/efeitos dos fármacos
18.
Clinics (Sao Paulo) ; 65(1): 23-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20126342

RESUMO

INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [(14)C]-cholesterol ester and [(3)H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m(2)] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 +/- 0.044 in the obese group and 0.122 +/- 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h(-1)) was 0.052 +/- 0.021 in the obese subjects and 0.058 +/- 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.


Assuntos
LDL-Colesterol/farmacocinética , Emulsões Gordurosas Intravenosas/farmacocinética , Nanopartículas , Obesidade/sangue , Adulto , Estudos de Casos e Controles , Emulsões Gordurosas Intravenosas/administração & dosagem , Emulsões Gordurosas Intravenosas/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem
19.
Rev. bras. med. esporte ; 16(1): 71-76, jan.-fev. 2010. tab
Artigo em Português | LILACS | ID: lil-553307

RESUMO

Os benefícios da prática regular do exercício físico estão claramente estabelecidos na literatura. Entretanto, a escolha do tipo de exercício ideal pode ser mais salutar para indivíduos com doenças específicas e patologias associadas. O propósito desta revisão foi verificar se o treinamento resistido (TR) exerce alguma alteração no colesterol da lipoproteína de baixa densidade (LDL-C). Foram observadas grandes diferenças na literatura, dificultando uma conclusão em relação aos benefícios do TR nesta revisão. No entanto, foi visto que o TR pode ser promissor na redução dos níveis de LDL-C, principalmente em homens e mulheres adultos, em pacientes com diabetes mellitus tipo 1 e tipo 2 e em mulheres pré-menopausa, não mostrando diferenças na população idosa. Os autores concluem que o TR é uma boa opção de exercício físico para indivíduos, principalmente quando o treinamento aeróbio (TA) é contraindicado.


The benefits of exercise regular practice are clearly established in the literature. However, the choice of the ideal exercise may be more beneficial for individuals with specific diseases and associated pathologies. The aim of this review was to determine whether resistance training (RT) promotes any change on low density lipoprotein cholesterol. Important differences were observed in research protocols, making it difficult to define the benefits of RT in this review. However, it was noticed that RT may be promising in reducing LDL-C levels mainly in adult men and women, in patients with diabetes mellitus type 1 and type 2 and in pre-menopausal women, not presenting differences in the elderly population. It was concluded that the RT is an option good of physical exercise for individuals, especially when the aerobic training (AT) is contra-indicated.


Assuntos
LDL-Colesterol/análise , Lipoproteínas/análise , Treinamento de Resistência/métodos
20.
Clinics ; 65(1): 23-27, 2010. tab, graf
Artigo em Inglês | LILACS | ID: lil-538603

RESUMO

Introduction: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. Objective: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. Methods: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. Results: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h-1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. Conclusion: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , LDL-Colesterol/farmacocinética , Emulsões Gordurosas Intravenosas/farmacocinética , Nanopartículas , Obesidade/sangue , Estudos de Casos e Controles , Emulsões Gordurosas Intravenosas/administração & dosagem , Emulsões Gordurosas Intravenosas/química , Nanopartículas/administração & dosagem
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