The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

Papel protector de las lipoproteínas de alta densidad en sepsis: aspectos básicos e implicancias clínicas / Protective role of high density lipoproteins in sepsis: basic issues and clinical implications

High density lipoproteins (HDL) are responsible of reverse cholesterol transport and play an important antiatherogenic role. In recent years, several studies suggest that HDL have additional functions, including a possible anti-inflammatory activity in infectious conditions. Furthermore, available evidence indicates that the presence of lipopolysaccharide (LPS) within the circulation during infectious states induced by gram-negative bacteria may be involved in the decrease in HDL cholesterol levels and changes in lipoprotein composition, which have been associated with a higher mortality due to sepsis in animal models and in humans. In this article, we review this subject and also discuss possible mechanisms that explain the positive impact achieved by native HDL, reconstituted HDL, or HDL apolipoprotein peptides on the inflammatory response and mortality in models of endotoxemia. In this regard, it has been proposed that one of the mechanisms by which HDL protect against sepsis may be mediated by its binding ability and/or neutralizing capacity on LPS, avoiding an excessive response of the immune system. Thus, increasing blood levels of HDL and/or parenteral HDL administration may represent a new anti-inflammatory tool for managing septic states in humans.

Las lipoproteínas de alta densidad (HDL) son responsables del transporte reverso de colesterol y ejercen un importante papel anti-aterogénico. En los últimos años, diversos estudios indican que las HDL también tendrían otras funciones críticas, incluyendo una posible actividad anti-inflamatoria durante estados infecciosos. Además, la evidencia disponible sugiere que la presencia de lipopolisacárido (LPS) en la circulación durante estados infecciosos inducidos por bacterias gramnegativas podría estar involucrado en la disminución del colesterol HDL y los cambios en composición de esta clase lipoproteínas, lo cual se asociaría con una mayor tasa de mortalidad por sepsis en modelos animales y en humanos. En este trabajo, se revisan los antecedentes mencionados y además se discuten posibles mecanismos que explican la disminución de la respuesta inflamatoria y de la mortalidad que se logran en modelos de endotoxemia tratados con HDL o preparaciones similares. En este sentido, se ha propuesto que uno de los mecanismos protectores de las HDL estaría mediado por su capacidad de unión y/o neutralización del LPS, evitando una respuesta exacerbada del sistema inmune. De esta manera, el aumento de los niveles sanguíneos de HDL y/o su administración parenteral podrían constituir nuevas herramientas anti-inflamatorias para el manejo de estados sépticos en humanos.

Levels of apolipoproteins as risk factors for coronary artery disease / Níveis de apolipoproteínas como fatores de risco para doença arterial coronariana

INTRODUCTION: The Saudi population is renowned for their unhealthy diet and physical inactivity. OBJECTIVE:To investigate apolipoproteins B (apo B), A-I (apo A-I) and B/A-I as risk factors that might be associated with increased incidence of the coronary artery disease. METHODS: Two hundred and twenty subjects suspected of having the coronary artery disease underwent coronary angiography and blood draw following a 12-hour fast. Apolipoproteins B and A-I were both measured by turbidimetric methods. RESULTS: One hundred and forty subjects were positive and 80 subjects were negative for the coronary artery disease. Both apolipoproteins were found to be statistically significant as risk factors for the coronary artery disease: apolipoprotein B (105.33±29.22 versus 94.56±24.35 mg/dL, p<0.003), apolipoprotein A-I (123.98±25.6 versus 133.5±24.1 mg/dL, p<0.004) and apolipoproteins B/A-I (0.88±0.28 versus 0.72±0.2, p<0.0001). CONCLUSIONS:Measurements of apolipoproteins B, A-I and calculation of apolipoproteins B/A-I ratio either instead of or in addition to the customary measurements of lipoprotein cholesterol may significantly add to predicting and assessing the coronary risk factors in the Saudi population.

INTRODUÇÃO: A população da Arábia Saudita é conhecida por sua dieta não-saudável e inatividade física. OBJETIVO: Investigar as apolipoproteínas B (apo B), AI (apo AI) e B/AI como fatores de risco que podem estar associados ao aumento da incidência da doença arterial coronariana. MÉTODOS: Duzentos e vinte pacientes com suspeita de doença art RESULTADOS: Cenerial coronariana foram submetidos à angiografia coronária e extração de sangue após jejum de 12 horas. As apolipoproteínas B e AI foram medidas por métodos turbidímetros.to e quarenta pacientes foram positivos e 80 foram negativos para a doença arterial coronariana. Ambas apolipoproteínas foram estatisticamente significativas como fatores de risco para doença arterial coronariana: apolipoproteínas B (105,33±29,22 versus 94,56±24,35 mg/dL, p<0,003), AI (123,98±25,6 versus 133,5±24,1, p<0,004) e B/A-I (0,88±0,28 versus 0,72±0,2, p<0,0001). CONCLUSÕES: As medidas das apolipoproteínas B, AI e o cálculo da relação B/AI tanto por ou em adição às medidas habituais de colesterol das lipoproteínas podem aumentar significativamente a previsão e avaliação dos fatores de risco coronariano na população saudita.

Factores de riesgo cardiovascular y perfil apolipoprotéico en un grupo de adultos atendidos en un centro público de salud del estado Carabobo, Venezuela / Cardiovascular risk factors and apolipoproteic profile in a group of adults treated in a public health center in Carabobo state, Venezuela

Objetivos. Comparar los niveles séricos de las apolipoproteínas A-I y B así como las relaciones Apo B/Apo A-I y HDL colesterol/Apo A-I según edad, sexo y factores de riesgo cardiovascular en individuos atendidos en un centro público de salud venezolano. Materiales y métodos. Se determinó la presión arterial, la circunferencia de cintura (CC), el perfil lipídico y las apolipoproteínas A-I y B en 221 individuos (44,0±15,5 años) de ambos sexos; también se calculó el índice de masa corporal (IMC) a partir del peso y la talla y se estableció hábito al tabaco, la ingesta de bebidas alcohólicas y el patrón de su consumo. Resultados. El 27,5 por ciento presentó concentraciones bajas de Apo A-I, 45,2 por ciento Apo B elevada y 60,6 por ciento relación Apo B/Apo A-I alta. Los niveles séricos de las apolipoproteínas y la relación Apo B/Apo A-I no variaron con la edad o sexo, mientras que la relación HDL colesterol/Apo A-I disminuyó al elevarse la edad. Los individuos obesos, fumadores, hipertensos, hipercolesterolémicos, hipertrigliceridémicos o con HDL colesterol bajo mostraron cifras más elevadas de Apo B y Apo B/Apo A-I. La relación HDL colesterol/Apo A-I disminuyó con la edad, el nivel de habito al tabaco y el aumento de LDL-C y triglicéridos. El consumo de tres o más bebidas alcohólicas/día se asoció con disminución de Apo B. Conclusiones. Se demostró alta prevalencia de perfil apolipoprotéico alterado, lo cual se asoció con los principales factores de riesgo cardiovascular. Los resultados del estudio apoyan la inclusión de las apolipoproteínas evaluadas en las determinaciones de laboratorio realizadas en los centros públicos de atención de salud venezolanos.

Objectives. To compare serum levels of apolipoproteins A-I and B as well as Apo B/Apo A-I and HDL cholesterol/Apo A-I ratios by age, gender and cardiovascular risk factors in individuals treated at a Venezuelan public health center. Materials and methods. We determined in 221 individuals (44.0 ± 15.5 years) of both genders blood pressure, waist circumference (WC), lipid profile and apolipoproteins A-I and B; body mass index (BMI) was calculated from weight and height; smoking habit, alcohol intake and consumption pattern were established. Results. 27.5 percent of individuals had low levels of Apo A-I, 45.2 percent high Apo B and 60.6 percent high Apo B/Apo A-I ratio. Serum levels of apolipoproteins and Apo B/Apo A-I ratio did not vary with age or gender, while the ratio HDL cholesterol/Apo A-I decreased with the age. Obese individuals, smokers, hypertensive, hypercholesterolemics, hypertriglyceridemics or with low HDL cholesterol showed higher Apo B and Apo B/Apo A-I ratio. Older individuals, smokers or individuals with increased LDL cholesterol and triglycerides showed lower HDL cholesterol/Apo A-I ratio. Consumption of three or more alcoholic drinks/day was associated with decreased Apo B. Conclusions. These results show high prevalence of altered apolipoprotein profile, which is associated with major cardiovascular risk factors. The results support the inclusion of the evaluated apolipoproteins in laboratory determinations made in public health centers in Venezuela.

Proteínas plasmáticas viscerales, malaria y desnutrición en niños colombianos / Visceral plasma proteins, malaria and malnutrition in Colombian children

Introducción: en América Latina y Colombia hay pocos informes sobre relaciones entre malaria e indicadores de estado nutricional. Objetivo: explorar correlaciones entre indicadores antropométricos y bioquímicos de desnutrición. Metodología: los niños (4-11 años, residentes en Turbo o El Bagre {Antioquia, Colombia}) participaron en dos proyectos diferentes, con diseño transversal, prospectivo. El primer estudio trabajó una muestra de 100 niños (4-9 años), 51 con paludismo y 49 sin la enfermedad. El segundo estudio evaluó 93 niños (4-10 años) con malaria, se trataron, se curaron y se reexaminaron el día 30, ya sin malaria. Se midieron dos indicadores antropométricos de desnutrición de largo plazo (peso/edad y talla/edad), cinco proteínas plasmáticas viscerales (albúmina, prealbúmina, apolipoproteína-A1, transferrina, ferritina), retinol, zinc, hemoglobina y proteína C reactiva PCR. Resultados: los coeficientes “r” significativos fueron débiles (r<0,600), positivos en general: a) Cuando había malaria: PCR con hemoglobina (negativa) y ferritina, hemoglobina-ferritina (negativa), retinol con zinc y prealbúmina, zinc con prealbúmina y ferritina, apoA1 con albúmina y transferrina; prealbúmina con albúmina y ferritina, albúmina con zinc y transferrina. b) Sin malaria: PCR con hemoglobina (negativa), ferritina, retinol (negativa) y apoA1 (negativa); retinol con hemoglobina, zinc y prealbúmina; zinc-prealbúmina; apoA1-albúmina; prealbúmina con albúmina y transferrina. Las únicas correlaciones significativas entre indicadores antropométricos y bioquímicos fueron: a) talla/edad con transferrina (negativa) cuando había malaria y con apolipoproteínaA1 (negativa) cuando no había paludismo (ambas p<0,10); b) peso/edad con apolipoproteínaA1: negativa con malaria, positiva sin malaria (ambas p<0,05). Conclusión: hubo varias correlaciones significativas entre indicadores bioquímicos nutricionales y prácticamente ninguna entre indicadores antropométricos y bioquímicos.

Introduction: in Latin America and Colombia, there are few reports about links between malaria and nutritional status indicators. Objective: to explore correlations between anthropometric and biochemical indicators of malnutrition. Methodology: children (aged 4-11 years; residing either in El Bagre or in Turbo [Antioquia, Colombia]) participated in two different projects, with prospective, cross design. The first study worked with a sample of 100 children (aged 4-9 years), 51 with malaria and 49 without the disease. The second study evaluated 93 children (aged 4-10 years) with malaria. They received treatment, were cured, and reexamined after a 30-day period, already without malaria. Two anthropometric indicators of long-term malnutrition (weight/age and height/age) were measured, as well as five visceral plasma proteins (albumin, prealbumin, apolipoprotein-A1, transferrin, ferritin), retinol, zinc, hemoglobin and C-reactive protein CRP. Results: significant “r” coefficients were weak (r <0600), generally positive: a) In the presence of malaria: CPR with hemoglobin (negative) and ferritin; hemoglobina-ferritina (negative); Retinol with zinc and prealbumin; zinc with prealbumin and ferritin; apoA1 with albumin and transferrin, ferritin and prealbumin albumin; albumin and transferrin with zinc. b) In the absence of malaria: PCR with hemoglobin (negative), ferritin, retinol (negative) and apoA1 (negative); Retinol with hemoglobin, zinc and prealbumin; zinc-prealbumin; apoA1-albúmina; prealbumin with albumin and transferrin. The only significant correlations between anthropometric and biochemical indicators were the following: a) height / age with transferrin (negative) in the presence of malaria and with apolipoproteínA1 (negative) in the absence of malaria (both p <0.10), b) weight / age with apolipoprotenA1: negative in the presence of malaria, positive in the absence of malaria (both p <0.05). Conclusion: there were several significant correlations between biochemical indicators and virtually none between anthropometric and biochemical indicators.

Heterogeneidade e mecanismos moleculares da atividade anti-apoptótica das subfrações de HDL em células endoteliais humanas / Heterogeneity and molecular mechanisms of anti-apoptotic activity of high-density lipoprotein (HDL) subfractions on endothelial cells

Introdução: A lipoproteína de baixa densidade (LDL) e suas formas oxidadas (LDLox) possuem múltiplas propriedades aterogênicas, atuando na deposição de colesterol, indução e manutenção da inflamação, disfunção endotelial, surgimento de células espumosas na parede arterial e conseqüente formação da placa de ateroma. Adicionalmente, LDLox induz apoptose de células endoteliais humanas (HMEC). A lipoproteína de alta densidade (HDL) possui inúmeras atividades antiaterogênicas, incluindo ações antioxidante, anti-inflamatória e anti-trombótica. A HDL é capaz de proteger as HMEC contra apoptose. As subfrações de HDL (sHDL) são heterogêneas em sua composição físico-química e atividades biológicas. A atividade antioxidante das sHDL aumenta com a densidade (HDL2b100% - anexina V) e 3b (43% e 67%, respectivamente) de indivíduos normolipidêmicos apresentaram atividade anti-apoptótica mais potente do que as subfrações HDL2a (29% e 28%; p<0,01 vs. HDL3c, respectivamente) e 2b (25% e 62%; p<0,001 vs. HDL3c, respectivamente). Todas sHDL reduziram geração de espécies reativas de oxigênio (ROS) induzida pela LDLox, sendo a HDL3c (54%) mais potente do que HDL2b (21%; p<0.05 vs. HDL3c). Houve correlação positiva entre as atividades anti-apoptótica e antioxidante intracelular com conteúdo de apoA-I e esfingosina 1-fosfato (E1F) das sHDL, senda HDL3b e 3c ricas em E1F. A atividade anti-apoptótica da E1F e das sHDL parece depender da interação com as células endoteliais via apoA-I e seu receptor SR-BI. Finalmente, as HDL3c (n=5) isoladas de pacientes com SMet possuem conteúdo significativamente menor de apoA-I e reduzida atividade anti-apoptótica (60%, p<0,01), quando comparada aos controles normolipidêmicos (n=5). Houve tendência à diminuição da proteção contra a geração de ROS (SMet, n=10). Conclusão: As subfrações HDL3c protegem de forma potente as células endoteliais humanas contra toxicidade e apoptose induzidas pela LDLox, assim como contra geração de ROS...

Background: Low density lipoprotein (LDL) and its oxidized forms (oxLDL) have several atherogenic properties, including cholesterol deposition, inflammation, endothelial dysfunction and foam cell formation on the arterial wall, leading to atherosclerotic plaque development. In addition, oxLDL induces human endothelial cell apoptosis (HMEC). High-density lipoprotein (HDL) has number of antiatherogenic activities, as antioxidative, anti-inflammatory and anti-thrombotic actions. HDL displays anti-apoptotic activity and is able to protect endothelial cells against oxLDL-induced apoptosis. HDL subfractions (sHDL) are highly heterogeneous in their physical and chemical composition and biological functions. Antioxidative activity of HDL subfractions increases with increment in density, HDL2b100% in annexin V biding) and 3b subfractions (43% and 67%, respectively) were more potent against oxLDL-induced toxicity and apoptosis as compared to HDL2a (29% and 28%; p<0.01 vs. HDL3c, respectively) and 2b subfractions (25% and 62%; p<0.001 vs. HDL3c, respectively). All HDL subfractions attenuated of reactive oxygen species (ROS) generation in HMEC induced by oxLDL. Again, HDL3c (54% inhibition) were more potent as compared to HDL2b (21%; p<0.05 vs. HDL3c). The anti-apoptotic and intracellular antioxidative activities of HDL3 were positively correlated with apoA-I and sphingosine 1-phosphate (S1P) content of sHDL and, possibly, depend on their cellular interaction through apoA-I and its SR-BI receptor. The sHDL3c isolated from MetS patients (n=5) possess reduced content of apoA-I and less potent anti-apoptotic activity (-60%, p<0.01) than controls (n=5). Conclusion: Normolipidemic small dense HDL3 provide potent protection of human endothelial cells from oxLDL-induced apoptosis; this anti-apoptotic activity is reduced in the MetS.