RESUMEN
A doença renal crônica (DRC) é uma condição clínica de alto risco cardiovascular e os pacientes nos estágios mais avançados da doença que dependem de terapia renal substitutiva frequentemente tem prejuízo cardiorespiratório, níveis elevados de pressão arterial (uso de múltiplas medicações para controle), modulação autonômica prejudicada e graus variados de inflamação. Deste modo este estudo tem como objetivo verificar se o exercício físico aeróbio intradialítico tem impacto em modificar estas alterações. Os pacientes foram selecionados em duas unidades de hemodiálise em São Luís do Maranhão, Brasil, entre junho de 2016 e outubro de 2019, e foram alocados conforme aceitação em grupo controle (GC) e grupo exercício (GE). O GE foi submetido a treinamento aeróbio com bicicleta por um período de 12 semanas. Avaliação física antropométrica, teste de caminhada de 6 minutos (TC6m), ecocardiograma, eletrocardiograma com análise da variabilidade da frequência cardíaca e medidas laboratoriais foram realizadas incluindo interleucina 6 (IL6) antes e após 12 semanas em ambos os grupos. Trinta e um pacientes foram avaliados 15 pacientes no grupo controle (GC) e 16 pacientes no grupo exercício (GE). Após 12 semanas de treinamento houve diminuição da pressão arterial sistólica do grupo exercício em relação ao basal (129,8 ± 9,41mmHg vs 112,00 ± 12,0 mmHg p = 0,03). Não houve alterações na composição corporal e na maioria dos exames laboratoriais, exceto pelo aumento do KTV (índice de adequação de diálise) e diminuição do LDL colesterol no grupo exercício em relação ao grupo controle. No entanto, os níveis de HDL colesterol aumentaram (39,92 ± 6,1 mg/dL vs 48,00 ± 7,85 mg/dL p = 0,02) e IL6 diminuíram (4,56 ± 1,2 pg / mL vs 2,14 ± 1,0 pg / mL p = 0,02). Houve aumento da distância percorrida no teste de caminhada no grupo exercício (473,80 ± 98,6 metros vs 573,50 ± 74,22 metros p = 0,01). Na avaliação ecocardiográfica, verificou-se que no GE houve diminuição da pressão da artéria pulmonar estimada (31,38 ± 2,9 mmhg vs 24,2 ± 1,7 mmhg p = 0,001). Houve melhora na modulação autonômica no GE (RMSSD 11,7 ± 4,2 vs 18,4 ± 5,7 p=0,02), LFnu (52,9 ± 17,2 vs 32,0 ± 18,2 p=0,02) e HFnu (48,1 ± 17,2 vs 68,0 ± 18,2 p=0,01). Não foram evidenciados efeitos adversos e não houve abandono do treinamento. Baseados nestes resultados, é possível concluir que o exercício aeróbio intradialítico por 12 semanas pode melhorar parâmetros cardiorrespiratórios, hemodinâmicos e autonômicos, com boa aderência e sem eventos adversos, podendo ser usado como medida coadjuvante para melhora clínica destes pacientes.
Chronic kidney disease (CKD) is a clinical condition of high cardiovascular risk and patients in the more advanced stages of the disease who depend on renal replacement therapy often experience cardiorespiratory impairment, high blood pressure levels (use of multiple medications for control), modulation impaired autonomy and varying degrees of inflammation. Thus, this study aims to verify whether intradialytic aerobic exercise has an impact on modifying these variables. The patients were selected in two hemodialysis units in São Luís do Maranhão, Brazil, between May 2016 and October 2019, and were allocated according to acceptance in the control group (CG) and exercise group (EG). The group exercise was submitted to aerobic exercise with bicycle for a period of 12 weeks. Anthropometric physical evaluation, 6-minute walk test (6MWT), echocardiogram, electrocardiogram with analysis of heart rate variability (VFC) and laboratory measurements were performed including interleukin 6 (IL6) before and after 12 weeks in both groups. Thirty-one patients were evaluated 15 patients in the control group (CG) and 16 patients in the exercise group (EG). After 12 weeks of training, there was a decrease in systolic blood pressure in the exercise group compared to baseline (129.8 ± 9.41 mmHg vs 112.00 ± 12.0 mmhg p = 0.03). There were no changes in body composition and in most laboratory tests, except for an increase in KTV (dialysis adequacy index) and a decrease in LDL cholesterol in the exercise group compared to the control group. However, HDL cholesterol levels increased (39.92 ± 6.1 mg / dL vs 48.00 ± 7.85 mg / dL p = 0.02) and IL6 decreased (4.56 ± 1.2 pg / mL vs 2.14 ± 1.0 pg / mL p = 0.02). There was an increase in the distance covered in the walking test in the exercise group (473.80 ± 98.6 m vs 573.50 ± 74.22 m p = 0,01). In the echocardiographic evaluation, it was found that in the EG there was a decrease in the estimated pulmonary artery pressure (31.38 ± 2.9 mmhg vs 24.2 ± 1.7 mmhg p = 0.001). There was an improvement in autonomic modulation in the EG (RMSSD 11.7 ± 4.2 vs 18.4 ± 5.7 p = 0.02), LFnu (52.9 ± 17.2 vs 32.0 ± 18.2 p = 0.02) and HFnu (48.1 ± 17.2 vs 68.0 ± 18.2 p = 0.01). There were no adverse effects and training was not abandoned. Based on these results, it is possible to conclude that intradialytic aerobic exercise for 12 weeks can improve cardiorespiratory, hemodynamic, and autonomic parameters, with good adherence and without adverse events, and can be used as a supporting measure for the clinical improvement of these patients.
Asunto(s)
Ejercicio Físico , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/fisiopatología , Arteria Pulmonar/fisiopatología , Presión Sanguínea , Ecocardiografía , Interleucina-6 , Terapia de Reemplazo Renal , Electrocardiografía , Presión Arterial , Prueba de Paso/instrumentación , Factores de Riesgo de Enfermedad Cardiaca , HDL-Colesterol/química , LDL-Colesterol/químicaRESUMEN
OBJECTIVE: To examine whether longitudinal changes in relative weight category (as indicated by change in body mass index [BMI] classification group) were associated with changes in nuclear magnetic resonance (NMR)-derived lipoprotein particles among US youth. STUDY DESIGN: Secondary analysis of data from a clustered randomized controlled trial. BMI and fasting blood samples were obtained from 2069 participants at the start of the 6th grade and end of the 8th grade. BMI was categorized as normal weight, overweight, or obese at both time points. Lipoprotein particle profiles were measured with NMR spectroscopy at both time points. Regression models were used to examine changes in relative weight group and change in lipoprotein variables. RESULTS: A total of 38% of participants changed relative weight category (BMI group) during the 2.5-year study period. Low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (HDL) cholesterol decreased almost universally, but more with improved BMI category. There were adverse effects on LDL size and total LDL particles, HDL size, and cholesterol for participants who remained obese or whose relative weight group worsened. Changes in relative category had no impact on HDL particles. CONCLUSION: Improvement in relative weight group from 6th to 8th grade was associated with favorable changes in non-HDL cholesterol, very low-density lipoprotein size, LDL size, HDL size, and LDL particles but had no effect on HDL particles. Findings indicate that an improvement in relative weight group between 6th and 8th grade had an effect on NMR-derived particles sizes and concentrations among a large group of adolescents, which overrepresented low-income minorities.
Asunto(s)
HDL-Colesterol/química , LDL-Colesterol/química , VLDL-Colesterol/química , Tamaño de la Partícula , Obesidad Infantil/sangre , Aumento de Peso , Pérdida de Peso , Adolescente , Biomarcadores/sangre , Biomarcadores/química , Índice de Masa Corporal , Niño , HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Espectroscopía de Resonancia Magnética , Masculino , Sobrepeso/sangre , Delgadez/sangreRESUMEN
Proanthocyanidins are the most abundant polyphenols in human diets. Epidemiological studies have pointed to proanthocyanidins as promising molecules that could prevent the development of several coronary syndromes by inhibiting the atherogenic process. The present study was designed to investigate the antiatherogenic effects of a proanthocyanidin-rich fraction (PRF) obtained from Croton celtidifolius Baill (Euphorbiaceae) barks. In isolated human LDL, PRF caused a concentration-dependent inhibition of Cu2+-induced oxidative modifications, evidenced by the increasing of the lag phase of lipid peroxidation and decreasing in the oxidation rate (Vmax), moreover, the protein moieties from LDL were protected against Cu2+-induced oxidation. In human umbilical vein endothelial cells (HUVECs), PRF reduced the ROS production stimulated by oxidized LDL. Herein, we demonstrate that oral treatment with PRF improved endothelium-dependent vasorelaxation in hypercholesterolemic LDL receptor knockout mice (LDLr-/-), however, the fraction did not modify plasma lipids and atherosclerotic lesion size in this experimental model. Finally, our results showed for the first time that PRF prevent isolated LDL oxidation, decrease oxidative stress in endothelial cells and improve endothelial function in mice.
Asunto(s)
Enfermedad de la Arteria Coronaria/prevención & control , Croton/química , Extractos Vegetales/farmacología , Proantocianidinas/farmacología , Animales , Células Cultivadas , LDL-Colesterol/química , Cobre , Células Endoteliales/efectos de los fármacos , Ratones , Ratones Noqueados , Oxidación-Reducción , Estrés Oxidativo , Corteza de la Planta/química , Extractos Vegetales/química , Proantocianidinas/química , Receptores de LDL/genética , Receptores de LDL/metabolismo , Vasodilatación/efectos de los fármacosRESUMEN
Leishmaniasis is a set of clinically distinct infectious diseases caused by Leishmania, a genus of flagellated protozoan parasites, that affects ~12 million people worldwide, with ~2 million new infections annually. Plants are known to produce substances to defend themselves against pathogens and predators. In the genus Lycopersicon, which includes the tomato, L. esculentum, the main antimicrobial compound is the steroidal glycoalkaloid α-tomatine. The loss of the saccharide side-chain of tomatine yields the aglycone tomatidine. In the present study, we investigated the effects of tomatidine on the growth, mitochondrial membrane potential, sterol metabolism, and ultrastructure of Leishmania amazonensis promastigotes. Tomatidine (0·1 to 5 µM) inhibited parasite growth in a dose-dependent manner (IC(50)=124±59 nM). Transmission electron microscopy revealed lesions in the mitochondrial ultrastructure and the presence of large vacuoles and lipid storage bodies in the cytoplasm. These structural changes in the mitochondria were accompanied by an effective loss of mitochondrial membrane potential and a decrease in ATP levels. An analysis of the neutral lipid content revealed a large depletion of endogenous 24-alkylated sterols such as 24-methylene-cholesta-5, 7-dien-3ß-ol (5-dehydroepisterol), with a concomitant accumulation of cholesta-8, 24-dien-3ß-ol (zymosterol), which implied a perturbation in the cellular lipid content. These results are consistent with an inhibition of 24-sterol methyltransferase, an important enzyme responsible for the methylation of sterols at the 24 position, which is an essential step in the production of ergosterol and other 24-methyl sterols.
Asunto(s)
Antiparasitarios/farmacología , Leishmania/efectos de los fármacos , Esteroles/biosíntesis , Tomatina/análogos & derivados , Adenosina Trifosfato/metabolismo , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Radioisótopos de Yodo/química , Leishmania/metabolismo , Leishmania/ultraestructura , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Tomatina/química , Tomatina/farmacologíaRESUMEN
Nitric oxide-releasing alpha-tocopherol mimetics with LDL-protective activity were designed to maintain the tocopherol substructure necessary for its biochemical recognition by alpha-tocopherol transfer protein. In order to study the molecular interactions to alpha-TTP, theoretical binding studies by means of docking techniques and experimental binding assays, using a fluorescent probe, were performed. Furoxanyl-tocopherol-hybrid analogs 7 and 9 have the best ability to bind to alpha-TTP suggesting that they could be incorporated to LDL in vivo to further release nitric oxide and prevent oxidative modifications.
Asunto(s)
Antioxidantes/metabolismo , Donantes de Óxido Nítrico/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Tocoferoles/metabolismo , Vitamina E/metabolismo , alfa-Tocoferol , Sustitución de Aminoácidos , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Humanos , Datos de Secuencia Molecular , Unión Proteica , Conformación Proteica , Relación Estructura-ActividadRESUMEN
La posibilidad de prevenir la aparición y progresión de la estenosis valvular aórtica calcificada tiene gran trascendencia debido a que es la tercera causa de enfermedad cardiovascular, puede diagnosticarse precozmente y evoluciona en forma lenta. Los estudios histológicos en la fase precoz de la enfermedad muestran lesiones muy parecidas a la aterosclerosis, los hallazgos bioquímicos son también muy parecidos en esa fase, aunque más tarde se orientan a la calcificación valvular y a la formación de hueso. Se han desarrollado dos modelos experimentales animales, el conejo alimentado con una dieta rica en colesterol y el ratón con déficit de apolipoproteína E en los que pueden observarse cambios histológicos, bioquímicos y hemodinámicos similares a la estenosis aórtica calcificada, que pueden prevenirse con estatinas. Existen seis estudios retrospectivos en seres humanos en los que se analiza el efecto de la administración de estatinas; en ellos se demuestra enlentecimiento en la progresión de la enfermedad asociada con los niveles bajos de LDL colesterol o con la administración del tratamiento. En estos estudios se administró la medicación a quienes tenían más factores de riesgo
Asunto(s)
Animales , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/fisiopatología , LDL-Colesterol/químicaRESUMEN
La posibilidad de prevenir la aparición y progresión de la estenosis valvular aórtica calcificada tiene gran trascendencia debido a que es la tercera causa de enfermedad cardiovascular, puede diagnosticarse precozmente y evoluciona en forma lenta. Los estudios histológicos en la fase precoz de la enfermedad muestran lesiones muy parecidas a la aterosclerosis, los hallazgos bioquímicos son también muy parecidos en esa fase, aunque más tarde se orientan a la calcificación valvular y a la formación de hueso. Se han desarrollado dos modelos experimentales animales, el conejo alimentado con una dieta rica en colesterol y el ratón con déficit de apolipoproteína E en los que pueden observarse cambios histológicos, bioquímicos y hemodinámicos similares a la estenosis aórtica calcificada, que pueden prevenirse con estatinas. Existen seis estudios retrospectivos en seres humanos en los que se analiza el efecto de la administración de estatinas; en ellos se demuestra enlentecimiento en la progresión de la enfermedad asociada con los niveles bajos de LDL colesterol o con la administración del tratamiento. En estos estudios se administró la medicación a quienes tenían más factores de riesgo.
Asunto(s)
Animales , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/fisiopatología , LDL-Colesterol/químicaRESUMEN
Cu(II) mediated low density lipoprotein (LDL) oxidation has been followed by the changes in absorbance at 234 nm and the emitted low level chemiluminescence (CL). The similarity of the time profiles allows us to conclude that the emitted CL is due to the decomposition of a transient product, most likely a hydroperoxide. Red wine, as well as its fractions, afford a noticeable protection when added prior to the start of the LDL oxidation process. On the other hand, when they are added after the onset of the autocatalytic oxidation phase, red wine and its fractions behave as pro-oxidants. This is particularly evidenced by a strong burst of CL (enhancement of the light by a factor approximately 20). This burst is reduced by metal chelators (EDTA and DFO) and can be associated to a sequence of reactions such as XOH + Cu(II) --> X* + H(+) + Cu(I), Cu(I) + LOOH --> chemiluminescence where XOH is a phenolic compound and LOOH is a peroxide-like compound produced in the LDL oxidation.
Asunto(s)
Antioxidantes/química , LDL-Colesterol/química , Cobre/química , Mediciones Luminiscentes , Especies Reactivas de Oxígeno/química , Vino/análisis , Absorción , Benzotiazoles , Depuradores de Radicales Libres/química , Humanos , Hierro/química , Cinética , Oxidación-Reducción , Ácidos Sulfónicos/química , Factores de TiempoRESUMEN
BACKGROUND: An increased incidence of coronary artery disease (CAD) is prevalent in northern Mexico. Effects of specific dietary components on risk factors for CAD have not been evaluated in children. OBJECTIVE: The purpose was to evaluate the effects of dietary cholesterol provided by whole eggs on the lipoprotein profile, LDL size, and phenotype in children from this region. DESIGN: Children (29 girls and 25 boys aged 8-12 y) were randomly assigned to either 2 eggs/d (EGG period; 518 additional mg cholesterol) or the equivalent amount of egg whites (SUB period; 0 additional mg cholesterol) for 30 d. After a 3-wk washout period, the children were assigned to the alternate treatment. RESULTS: Subjects were classified as hyporesponders (no increase or /=0.06 mmol/L increase). During the EGG period, the hyperresponders (n = 18) had an elevation in both LDL cholesterol (from 1.54 +/- 0.38 to 1.93 +/- 0.36 mmol/L) and HDL cholesterol (from 1.23 +/- 0.26 to 1.35 +/- 0.29 mmol/L) with no changes in LDL:HDL. In contrast, hyporesponders (n = 36) had no significant alterations in plasma LDL or HDL cholesterol. All subjects had an increase in LDL peak diameter during the EGG period (P < 0.01) and a decrease (P < 0.01) in the smaller LDL subfractions. In addition, 5 of the children having LDL phenotype B (15%) shifted from this high-risk pattern to pattern A after the EGG treatment. CONCLUSIONS: Intake of 2 eggs/d results in the maintenance of LDL:HDL and in the generation of a less atherogenic LDL in this population of Mexican children.
Asunto(s)
Colesterol en la Dieta/administración & dosificación , Colesterol en la Dieta/metabolismo , Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Análisis de Varianza , Biomarcadores/sangre , Niño , Colesterol/metabolismo , HDL-Colesterol/sangre , HDL-Colesterol/metabolismo , LDL-Colesterol/sangre , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/metabolismo , Estudios Cruzados , Huevos , Femenino , Humanos , Masculino , México/epidemiología , Tamaño de la Partícula , Fenotipo , Factores de RiesgoRESUMEN
The objective of the present study was to identify disturbances of nitric oxide radical (.NO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of.NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 +/- 9.7 years; blood pressure, 148.3 +/- 24.8/90.8 +/- 10.2 mmHg) and in 11 healthy subjects (N: 48.4 +/- 7.0 years; blood pressure, 119.4 +/- 9.4/75.0 +/- 8.0 mmHg). Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 +/- 26.0, N: 54.2 +/- 24.9 micro M), urate (H: 108.5 +/- 18.9, N: 156.4 +/- 26.3 micro M), beta-carotene (H: 1.1 +/- 0.8, N: 2.5 +/- 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 +/- 0.2, N: 0.7 +/- 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3beta,5,6beta-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 +/- 0.2, N: 0.7 +/- 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for.NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although.NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.
Asunto(s)
Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Peroxidación de Lípido/fisiología , Óxido Nítrico/sangre , Estrés Oxidativo/fisiología , Vasodilatación/fisiología , Adulto , Anciano , Disponibilidad Biológica , Estudios de Casos y Controles , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Cromatografía , Endotelina-1/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana EdadRESUMEN
AIMS: The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. METHODS: The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation. RESULTS: At baseline all groups were well matched regarding all variables. After 8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in a dose-dependent manner increased the lag phase of conjugated diene generation (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from 8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found. CONCLUSIONS: The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.