Claude Louis Léger

Grape and grape seed extract capacities at protecting LDL against oxidation generated by Cu2+, AAPH or SIN-1 and at decreasing superoxide THP-1 cell production. A comparison to other extracts or compounds.

A large body of evidence supports the key role of oxidized low-density lipoprotein in atherosclerosis. The aim of this study was to compare the capacity of natural polyphenols (PP) from Vitis vinifera and Olea europea at protecting LDL against oxidation brought about by Cu 2+ , oxygen-centered radical-generating AAPH, or peroxynitrite-generating SIN-1 in vitro systems, or at impairing superoxide production in promonocyte cells (THP-1) conveniently differentiated into adherent macrophages. PP were either from the whole grape (fraction A) containing mainly procyanidins, (epi)-catechin and anthocyanins, or from grape seed extracts (fractions B and C) consisting of tannins and procyanidin oligomers with a higher content in B than in C, or from a grape skin extract (fraction D) consisting mainly of anthocyanins, or from a hydrosoluble olive mill wastewater PP extract (fraction E) containing hydroxytyrosol and oleuropein. Chlorogenic acid (F) and catechin (G) were taken as archetypes of PP preventing oxidation partly as copper scavenger and as radical scavenger only, respectively. All grape fractions were efficient towards Cu 2+ system (equally or more efficient than F), whereas they were rather poorly efficient towards AAPH and SIN-1 (less efficient than G but as efficient as F). Among the PP fractions, B was the most effective at protecting LDL in the SIN-1 system and at impairing THP-1 superoxide production. Taken together, these data suggest that the PP fraction from grape seed rich in procyanidins achieves the best compromise between the direct and indirect (i.e. cell-mediated) types of action in protecting LDL against oxidation, strengthening the need for improving the knowledge of its bioavailability in humans.

Red-wine beneficial long-term effect on lipids but not on antioxidant characteristics in plasma in a study comparing three types of wine--description of two O-methylated derivatives of gallic acid in humans.

The purpose of this double clinical study was (1) to evaluate the effect of one single intake (300 ml) of red wine (RW) on the plasma antioxidant capacity (pAOC) and plasma phenolics over the 24-h time period following the intake, and (2) to compare the long-term effects of daily intakes (250 ml/d) of RW, white wine (WW) and Champagne (CH) on the plasma and LDL characteristics of healthy sujects. In the first part, blood samples were collected just before and after wine consumption. In the second part, subjects received the 3 types of wine successively, only at the mealtime, over 3-week periods separated by a 3-week wash out. Blood samples were drawn in fasting condition before and after each 3-week wine consumption period. The peak of pAOC was at 3-4 h following the single intake of RW, that of catechin was at 4 h (0.13 μmol/l) and that of gallic acid and caffeic acid was earlier (≤⃒1.5 and 0.3 μmol/l, respectively). In plasma, the major form of gallic acid was 4-O-methylated, but a minor form (the 3-O-methyl derivative) appeared. In the long term study, no wine was able to change LDL oxidizability, but some other parameters were modified specifically: RW decreased pAOC (without changing TBARS and uric acid plasma levels), LDL lipids and total cholesterol (TC), and increased plasma apoA1, whereas CH increased plasma vitamin A. The beneficial effect of RW seems to mainly be explained by its action on lipid and lipoprotein constants, and not by its antioxidant one.

Diagnosis of iron deficiency anemia in children of Northeast Brazil

OBJECTIVE To diagnose iron deficiency anemia in children. METHODS The study was conducted with a sample of 301 children aged six to 30 months attending public daycare centers in the city of Recife, Northeast Brazil, in 2004. The diagnoses of anemia were based on a combination of different hematological and biochemical parameters: hemoglobin, mean corpuscular volume, ferritin, C-reactive protein, transferrin saturation and transferrin receptor. The chi-square test and ANOVA were used in the statistical analysis. RESULTS Of all children studied, 92.4% had anemia (Hb<110 g/L) and 28.9% had moderate/severe anemia (Hb<90 g/L). Lower levels of hemoglobin were found in children aged 6-17 months. Iron deficiency was found in 51.5% of children using ferritin (<12 microg/L) as parameter. Taking into consideration the combination of hemoglobin level, ferritin and transferrin receptor, 58.1% had anemia with iron deficiency, 34.2% had anemia without iron deficiency and 2.3% had iron deficiency without anemia. Mean ferritin concentration was significantly higher in children with high C-reactive protein when compared with those with normal levels (22.1 vs. 14.8 microg/L). CONCLUSIONS The use of several biochemical and hematological parameters allowed to diagnosing iron deficiency anemia in two thirds of children, suggesting a need to identify other determinants of anemia without iron deficiency.OBJETIVO: Diagnosticar anemia por deficiencia de ferro em criancas. METODOS: O estudo foi desenvolvido com uma amostra de 301 criancas com idade entre seis e 30 meses, usuarias de creches publicas de Recife, PE, em 2004. Para o diagnostico da anemia utilizou-se a combinacao de diferentes parâmetros hematologicos e bioquimicos: hemoglobina, volume corpuscular medio, ferritina, proteina C-reativa, saturacao da transferrina e receptor da transferrina. Para a analise estatistica empregou-se o teste do qui-quadrado e ANOVA. RESULTADOS: Do total de criancas, 92,4% tinha anemia (Hb < 110g/L) e 28,9% apresentou anemia moderada/grave (Hb<90g/L). Niveis mais baixos de hemoglobina foram observados em criancas de seis a 17 meses. Encontrou-se deficiencia de ferro em 51,5% das criancas, utilizando-se a ferritina (< 12µg/L) como parâmetro. Considerando a combinacao da concentracao de hemoglobina, ferritina e do receptor de transferrina, 58,1% tinha anemia com deficiencia de ferro, 34,2% anemia sem deficit de ferro e 2,3% deficiencia de ferro sem anemia. A concentracao media de ferritina foi significativamente maior em criancas com proteina C-reativa aumentada quando comparada com aqueles com niveis normais (22,1 versus 14,8 µg/L). CONCLUSOES: A utilizacao de diversos parâmetros bioquimicos e hematologicos possibilitou diagnosticar anemia por deficiencia de ferro em dois tercos das criancas, revelando a necessidade de identificar outros determinantes de anemia sem deficiencia de ferro.

Monocyte superoxide production is inversely related to normal content of α-tocopherol in low-density lipoprotein

Vitamin E (alpha-tocopherol) is a potent peroxyl radical scavenger. According to the oxidative theory of atherosclerosis, it prevents oxidation of low-density lipoprotein (LDL) and thereby lowers the risk of cardiovascular disease. It also mediates cell actions, and specifically decreases monocyte superoxide anion-production (O2.--production), which is involved in LDL oxidation. We investigated whether alpha-tocopherol-containing LDL decreases this production in a manner dependent on the LDL alpha-tocopherol content (the alpha-tocopherol/apoB molar ratio) in human, phorbol ester-stimulated, adherent monocytes. We found that O2.--production was inhibited by native LDL (n-LDL) in a manner highly sensitive to the increasing alpha-tocopherol content (range 4.5 8). In addition: (1) inhibition was greater when alpha-tocopherol was associated to acetylated LDL (ac-LDL), the maximal percentage of inhibition being 80% as opposed to 35% for n-LDL; (2) the alpha-tocopherol overloading of either form of LDL did not produce further inhibition; (3) the free form of alpha-tocopherol produced lower inhibition compared with the lipoprotein-associated forms; (4) inhibition was not related to the cell content of alpha-tocopherol. We propose that the cell targeting of alpha-tocopherol is crucial to the inhibition of monocyte O2.--production, and thus that the role of normal LDL-alpha-tocopherol contents (range 6-8) in the prevention of atherogenic processes needs to be reexamined.

Saúde e nutrição de crianças de áreas urbanas da Zona da Mata Meridional de Pernambuco: resultados preliminares de um estudo de coorte

OBJECTIVES: to demonstrate social, economic features and demographics of the nutritional profile of children at birth and at 12 months old, in addition to comprehensive data on breast-feeding, diarrhea and vaccination status in the first year of life. METHODS: a sample of 652 newborns were selected from September 1997 to August 1998 and followed-up during the first 18 months of life. These children lived in the urban areas of four municipalities South of Pernambuco. Data collection was performed through house visits. RESULTS: approximately 60% of the families had a per capita income £ ½ of the minimum wage and 41% of the mothers had less than four years of schooling. The median of exclusive and total breast-feeding was of 0 and 94 days respectively. Diarrhea incidence was of two episodes/per child/per age (< -2 scores z) and at 12 months was of 6,8% and 11% respectively. Only 66% of the children had their vaccination schedule completed at 12 months old. CONCLUSIONS: the development of this prospective research will contribute to a more in-depth understanding of the health and nutrition problems of children and to adequate intervention planning in that area.

Potential anti-atherogenic cell action of the naturally occurring 4-O-methyl derivative of gallic acid on Ang II-treated macrophages.

We have recently established that the blood concentrations of gallic acid (GA), a polyphenolic component naturally found in food, and its O‐methyl derivatives are very low (practically ⩽1 μM) in physiological (postprandial) condition. Using acellular oxidant systems and macrophage‐differentiated promonocytes (MDPs) THP‐1, we show here that the direct and indirect (through depressing effect on the superoxide cell production) antioxidant properties of these components were not effective at these concentrations. In contrast, 4‐O‐methyl GA was the most efficient component to depress AT1R and CD36 mRNA expression in Ang II‐treated MDPs, suggesting a strong inhibition of Ang II‐triggered pro‐atherogenic mechanisms of foam cell formation.

Diagnóstico de anemia por deficiência de ferro em crianças do Nordeste do Brasil

OBJECTIVE To diagnose iron deficiency anemia in children. METHODS The study was conducted with a sample of 301 children aged six to 30 months attending public daycare centers in the city of Recife, Northeast Brazil, in 2004. The diagnoses of anemia were based on a combination of different hematological and biochemical parameters: hemoglobin, mean corpuscular volume, ferritin, C-reactive protein, transferrin saturation and transferrin receptor. The chi-square test and ANOVA were used in the statistical analysis. RESULTS Of all children studied, 92.4% had anemia (Hb<110 g/L) and 28.9% had moderate/severe anemia (Hb<90 g/L). Lower levels of hemoglobin were found in children aged 6-17 months. Iron deficiency was found in 51.5% of children using ferritin (<12 microg/L) as parameter. Taking into consideration the combination of hemoglobin level, ferritin and transferrin receptor, 58.1% had anemia with iron deficiency, 34.2% had anemia without iron deficiency and 2.3% had iron deficiency without anemia. Mean ferritin concentration was significantly higher in children with high C-reactive protein when compared with those with normal levels (22.1 vs. 14.8 microg/L). CONCLUSIONS The use of several biochemical and hematological parameters allowed to diagnosing iron deficiency anemia in two thirds of children, suggesting a need to identify other determinants of anemia without iron deficiency.OBJETIVO: Diagnosticar anemia por deficiencia de ferro em criancas. METODOS: O estudo foi desenvolvido com uma amostra de 301 criancas com idade entre seis e 30 meses, usuarias de creches publicas de Recife, PE, em 2004. Para o diagnostico da anemia utilizou-se a combinacao de diferentes parâmetros hematologicos e bioquimicos: hemoglobina, volume corpuscular medio, ferritina, proteina C-reativa, saturacao da transferrina e receptor da transferrina. Para a analise estatistica empregou-se o teste do qui-quadrado e ANOVA. RESULTADOS: Do total de criancas, 92,4% tinha anemia (Hb < 110g/L) e 28,9% apresentou anemia moderada/grave (Hb<90g/L). Niveis mais baixos de hemoglobina foram observados em criancas de seis a 17 meses. Encontrou-se deficiencia de ferro em 51,5% das criancas, utilizando-se a ferritina (< 12µg/L) como parâmetro. Considerando a combinacao da concentracao de hemoglobina, ferritina e do receptor de transferrina, 58,1% tinha anemia com deficiencia de ferro, 34,2% anemia sem deficit de ferro e 2,3% deficiencia de ferro sem anemia. A concentracao media de ferritina foi significativamente maior em criancas com proteina C-reativa aumentada quando comparada com aqueles com niveis normais (22,1 versus 14,8 µg/L). CONCLUSOES: A utilizacao de diversos parâmetros bioquimicos e hematologicos possibilitou diagnosticar anemia por deficiencia de ferro em dois tercos das criancas, revelando a necessidade de identificar outros determinantes de anemia sem deficiencia de ferro.

Renal Effects of Essential Fatty Acid Deficiency in Hydropenic and Volume-Expanded Rats

The aim of this paper was to study the effects of essential fatty acid (EFA) on fractional sodium excretion (FENa+) and renal hemodynamics in rats during hydropenia (H) and acute volume expansion (VE), successively. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured using a blood pressure transducer and a flow probe, respectively, both connected to a flowmeter. Glomerular filtration rate (GFR) was estimated by inulin clearance. The rats receiving coconut oil as only source of dietary lipids (the EFA-deficient group) presented lower levels of linoleic acid in cortex and medulla and lower body weight than the rats receiving soy oil in place of coconut oil (the control non-EFA-deficient group). During H, the EFA-deficient rats exhibited a lower level of renal vascular resistance resulting in a higher level of RBF and a higher urinary flow (V’) and FENa+, although GFR was lower than in the control group. During VE, the rats of the control group responded with increased MAP, RBF, V’ and FENa+, which were not found in the EFA-deficient group, suggesting an impaired hemodynamic adjustment in EFA deficiency. In conclusion, both experimental conditions revealed that EFA deficiency affects the renal hemodynamics.

Impairment of antioxidant defense mechanisms in elderly women without increase in oxidative stress markers: “A weak equilibrium”

The free radical theory of aging suggests that progressive defects in protection against free radicals allow tissue damage to occur. Concordant data have been observed in cell cultures or in animal models of aging. However, previous findings on antioxidant levels in human blood are somewhat conflicting according to the inclusion criteria (age, intercurrent diseases, habitus). Oxidative metabolism was investigated in 198 elderly healthy women more than 75 yr old (81.6 + 3.7; 75-99) living at home. Oxidative stress was evaluated by determining: the end product of lipid peroxidation, malondialdehyde (TBARS), and plasma and red blood cell (RBC) lipid content in polyunsaturated fatty acids (PUFA); nonenzymatic antioxidant system: plasma and RBC ot-tocopherol (pl Vit. E and RBC Vit. E), RBC glutathione (GSH); enzymatic antioxidant: RBC superoxide dismutase (SOD) and plasma glutathione peroxidase (GPx); and trace elements (copper, zinc, selenium). Nutritional status was monitored by body mass index, caloric intake, protein and lipid markers of malnutrition (albumin, prealbumin, retinol-binding protein, cholesterol, and triglycerides). Results were compared to a control group of 50 healthy young women (age range 20-45 yr). Despite reduced caloric intake (average 1582 kcal, range 697-3352), elderly women did not have any clinical (body mass index: 25 kg/m 2) or biological criteria of malnutrition: albumin (43.9 -+ 3.4 vs. 40.5 _+ 3.1 g/L; P < 0.001 ), prealburain (0.34 _+ 0.17 vs. 0.29 _+ 0,1 g/L; P < 0.01), retinol-binding protein (44.8 _+ 10 vs. 43.7 + 11 rag/L), cholesterol (6.13 +_ 1.1 vs. 5.12 _+ 0.95 mmol/L; P < 0.001), and triglycerides (1.18 + 0.56 vs. 0.99 _+ 0.45 mmol/L) were similar or increased in elderly vs. young women, respectively. When compared to healthy volunteers, SOD activity (I . 16 _+ 0.23 vs. 1.28 + 0.25 U/rag Hb, P < 0.01) and RBC GSH (4.32 + 1.10 vs. 4.69 -+ 1.06 nmol/mg Hb, P < 0.05) were significantly decreased, whereas pl Vit. E, RBC Vit. E, and GPx remained unchanged; copper (1.17 -+ 0.21 vs. 1.31 -+ 0.38 mg/L; P < 0,001) and zinc levels (0.86 + 0.16 vs. 0.94 _+ 0.16 rag/L; P < 0.01) were decreased; by contrast selenium levels were unaffected (75 _+ 22 vs. 80 + 17 ~tg/L). Despite these impairments in antioxidant defense mechanisms, we did not observe any increase in TBARS level ( l .26 +_ 0.36 vs. 1.34 + 0.37 mmol/L) or a decrease in PUFA content in plasma and RBC phospholipids. In healthy, well-nourished elderly populations, the impairment in antioxidant system did not result in an oxidative injury but in a precarious balance. This weak equilibrium could result in an increased susceptibility to reactive oxygen species and could be an underlying event for age-related diseases.

Ellagic acid and its methyl-derivatives inhibit a newly found nitratase activity.

We have recently shown that low density lipoprotein (LDL) was able to denitrate albumin‐bound 3‐NO2‐Tyr residues and to concomitantly release NO3− through a Ca2+‐dependent process that has been ascribed to a specific protein structure. A lipophilic food component (γ‐tocopherol), which is easily loaded into LDL has been found to totally inhibit denitrating activity. We presently found that ellagic acid (EA) and its methylated derivatives, 4,4′O‐methyl‐ and 3,3′O‐methyl‐ellagic acids (MeEA1 and MeEA2, respectively), amphipathic phenolic components of certain fruits and beverages, were also able to inhibit this activity, with a total inhibition for EA and a 60% inhibition for MeEA1 and MeEA2. EA exhibited the highest affinity for protein plasma, whereas a higher affinity of MeEA1 and MeEA2 (with MeEA1 > MeEA2) than EA was found for lipoprotein fractions, suggesting that the inhibition‐driving property is protein affinity. As a result of this nitratase‐inhibition property EA and its natural metabolite MeEA2 may have a beneficial role in special physiopathological conditions.