A Mediterranean Diet Rich in Extra-Virgin Olive Oil Is Associated with a Reduced Prevalence of Nonalcoholic Fatty Liver Disease in Older Individuals at High Cardiovascular Risk.

BACKGROUND: Adherence to a Mediterranean diet (MedDiet) is thought to reduce liver steatosis. OBJECTIVES: To explore the associations with liver steatosis of 3 different diets: a MedDiet + extra-virgin olive oil (EVOO), MedDiet + nuts, or a control diet. METHODS: This was a subgroup analysis nested within a multicenter, randomized, parallel-group clinical trial, PREvención con DIeta MEDiterránea (PREDIMED trial: ISRCTN35739639), aimed at assessing the effect of a MedDiet on the primary prevention of cardiovascular disease. One hundred men and women (mean age: 64 ± 6 y), at high cardiovascular risk (62% with type 2 diabetes) from the Bellvitge-PREDIMED center were randomly assigned to a MedDiet supplemented with EVOO, a MedDiet supplemented with mixed nuts, or a control diet (advice to reduce all dietary fat). No recommendations to lose weight or increase physical activity were given. Main measurements were the percentage of liver fat and the diagnosis of steatosis, which were determined by NMR imaging. The association of diet with liver fat content was analyzed by bivariate analysis after a median follow-up of 3 y. RESULTS: Baseline adiposity and cardiometabolic risk factors were similar among the 3 treatment arms. At 3 y after the intervention hepatic steatosis was present in 3 (8.8%), 12 (33.3%), and 10 (33.3%) of the participants in the MedDiet + EVOO, MedDiet + nuts, and control diet groups, respectively (P = 0.027). Respective mean values of liver fat content were 1.2%, 2.7%, and 4.1% (P = 0.07). A tendency toward significance was observed for the MedDiet + EVOO group compared with the control group. Median values of urinary 12(S)-hydroxyeicosatetraenoic acid/creatinine concentrations were significantly (P = 0.001) lower in the MedDiet + EVOO (2.3 ng/mg) than in the MedDiet + nuts (5.0 ng/mg) and control (3.9 ng/mg) groups. No differences in adiposity or glycemic control changes were seen between groups. CONCLUSIONS: An energy-unrestricted MedDiet supplemented with EVOO, a food with potent antioxidant and anti-inflammatory properties, is associated with a reduced prevalence of hepatic steatosis in older individuals at high cardiovascular risk.

A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women.

PURPOSE: Serum nitric oxide (NO) reduction and increased endothelin-1 (ET-1) play a pivotal role in endothelial dysfunction and hypertension. Considering that traditional Mediterranean diet (TMD) reduces blood pressure (BP), the aim of this study was to analyze whether TMD induced changes on endothelial physiology elements such as NO, ET-1 and ET-1 receptors which are involved in BP control. METHODS: Non-smoking women with moderate hypertension were submitted for 1 year to interventions promoting adherence to the TMD, one supplemented with extra virgin olive oil (EVOO) and the other with nuts versus a control low-fat diet (30 participants/group). BP, NO, ET-1 and related gene expression as well as oxidative stress biomarkers were measured. RESULTS: Serum NO and systolic BP (SBP) or diastolic BP (DBP) were negatively associated at baseline, as well as between NO and ET-1. Our findings also showed a DBP reduction with both interventions. A negative correlation was observed between changes in NO metabolites concentration and SBP or DBP after the intervention with TMD + EVOO (p = 0.033 and p = 0.044, respectively). SBP reduction was related to an impairment of serum ET-1 concentrations after the intervention with TMD + nuts (p = 0.008). We also observed changes in eNOS, caveolin 2 and ET-1 receptors gene expression which are related to NO metabolites levels and BP. CONCLUSIONS: The changes in NO and ET-1 as well as ET-1 receptors gene expression explain, at least partially, the effect of EVOO or nuts on lowering BP among hypertensive women.

Role of oxidative stress and adenosine nucleotides in the liver of aging rats.

We studied the response of several parameters related to oxidative stress in the liver of aging rats. Male Wistar rats aged 1.5, 3, 18 and 24 months were used. Livers showed an increase in superoxide anion (O(2)(-)) concentration at 1.5 and 18 months of age compared to the 3-month-old group; a decrease in superoxide dismutase (SOD) was seen at 1.5 months and catalase concentrations remained unaltered throughout the aging process. Nitric oxide (NO) progressively declined with age; a significant decrease was particularly apparent at 18 and 24 months of age. Thiobarbituric acid reactive substances (TBARS) decreased significantly at 1.5 months, whereas it increased at 18 and 24 months of age. Concentrations of prostaglandin E(2) (PGE(2)), and adenine nucleotides, and their metabolites, remained unchanged throughout the aging process. Although the mitochondrial damage caused by oxidative stress can result in reduced ATP production and compromised cell function, our results on adenosine nucleotides and their metabolites support the notion that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. In conclusion, we observed a significant decrease in the levels of NO in the older groups of rats and hence in its antioxidant activity. This could explain the observed increase in lipid peroxides which suggests an important role for NO in oxidative stress in the liver of older rats.

Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature. / Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica.

In differentiated thyroid cancer (DTC), radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy (ablative treatment), to treat residual microscopic disease (adjuvant treatment), and to treat macroscopic or metastatic disease. Currently, treatment of DTC with 131I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval. The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature. Pending the results of the prospective trials that are currently underway, the use of 131I seems to be justified not only in high-risk patients, but also in intermediate-risk and low-risk patients. The guidelines of The American and British Thyroid Association, European and American Societies of Nuclear Medicine, The European Consensus Group and the latest edition of National Comprehensive Cancer Network (NCCN) were considered in drawing up this continuing education document, we also undertook a review of the related scientific literature.

Results of a nationwide survey on multidisciplinary teams on thyroid cancer in Spain.

AIM: There is an important lack of knowledge as to the functioning of multidisciplinary teams on thyroid cancer in current clinical practice. We aimed to retrieve data on the composition, structure, and procedures developed by the multidisciplinary units of thyroid cancer in Spain. METHODS: A nationwide survey consisting of questions about composition, structure, and functioning of multidisciplinary teams was designed. It was available online from November 15, 2017 to February 15, 2018. RESULTS: Seventy-two multidisciplinary units responded to our survey. Of these, 15 (20.8%) focused only in thyroid cancer, while 57 (79.2%) included other endocrine disorders or non-endocrine tumors. The median (interquartile range) of members of the teams was 11 (9-14). The most frequent medical specialties in the units were endocrinology (100%), surgery (94.4%), pathology (80.6%), radiology (75.0%), nuclear medicine (73.6%), and medical oncology (55.6%). The annual number of patients reviewed by the teams was 40 (20-74). 56.9% of the multidisciplinary teams have elaborated clinical protocols for local use. Apart from clinical case discussions in the meetings, 45.8% of the units included educational activities and 36.1% research subjects. Quality indicators were developed by 22% of the teams. CONCLUSIONS: These results suggest that there are some hopeful signs that international recommendations of having multidisciplinary approach to patients with thyroid cancer are being followed in Spain. This gives us the opportunity to proceed with further studies to analyze the real impact of this high standard of care on patient outcomes.

Parameters of metabolic quantification in clinical practice. Is it now time to include them in reports? / Parámetros de cuantificación metabólica en la práctica clínica. ¿Es el momento de incluirlos en los informes?

Qualitative techniques have traditionally been the standard for the diagnostic assessment with 18F-FDG PET studies. Since the introduction of the technique, quantitative parameters have been sought, more accurate and with better diagnostic precision, that may offer relevant information of the behavior, aggressiveness or prognosis of tumors. Nowadays, more and more studies with high quality evidence show the utility of other metabolic parameters different from the SUV maximum, which despite being widely used in clinical practice is controversial and many physicians still do not know its real meaning. The objective of this paper has been to review the key concepts of these metabolic parameters that could be relevant in normal practice in the future. It has been seen that there is more evidence in the complete evaluation of the metabolism of a lesion, through volumetric parameters that more adequately reflect the patient's tumor burden. Basically, these parameters calculate the volume of tumor that fulfills certain characteristics. A software available in the majority of the workstations has been used for this purpose and it has allowed to calculate these volumes using more or less complex criteria. The simplest threshold-based segmentation methods are available in most equipments, they are easy to calculate and they have been shown in many studies to have an important prognostic significance.

Autocrine stimulation by erythropoietin and autonomous growth of human erythroid leukemic cells in vitro.

Autonomous colony formation is a frequent event in erythroleukemia. In 13 cases of early erythroid leukemias, we investigated whether erythropoietin (Epo) autocrine stimulation was responsible for the growth factor autonomy. Epo transcripts were detected by Northern blotting in cells from one patient. These cells also expressed an Epo receptor (1,000 receptors per cell) with a 420-pM affinity and Epo was detected in the supernatant of cultured cells. In 8 of the 13 cases, Epo transcripts were revealed by the polymerase chain reaction ranging from 0.5 to 500 copies per cell. In situ hybridization proved that these Epo transcripts were present in the blast cells. No Epo gene abnormalities were detected by Southern blotting. In two cases, leukemic cells were grown in the presence of Epo-neutralizing antibodies or Epo antisense oligomers. In one case, the antibody significantly reduced autonomous growth. In contrast, the antibody had no effect in the second case in which blast cells transcribed the Epo gene at a low level. However, Epo antisense oligomers partially inhibited autonomous growth. This inhibition was reversed by addition of exogenous Epo. Overall, these results suggest that an extracellular or intracellular autocrine Epo stimulation occurs in some cases of erythroid malignancies.

Loss of adaptation to oxidative stress as a mechanism for aortic damage in aging rats.

Cells are armed with a vast repertoire of antioxidant defence mechanisms to prevent the accumulation of oxidative damage. The cellular adaptive response is an important antioxidant mechanism against physiological and pathophysiological oxidative alterations in a cell's microenvironment. The aim of this paper was to study, in the rat aorta, whether this adaptive response and the inflammation associated with oxidative stress were expressed throughout the aging process. We examined the rat aorta, as it is a very sensitive tissue to oxidative stress. Male Wistar rats of 1.5, 3, 12, 18 and 24 months of age were used. Superoxide anion (O2(-)) generation; levels of two antioxidant enzymes, superoxide dismutase (SOD) and catalase; and the levels of prostaglandin E2 (PGE2), an inflammatory marker, were measured. The results for rats at different ages were compared with those for 3 months of age. A balance between production of O2(-) and SOD activity was found in the aorta of rats from 1.5 to 12 months old. Oxidative stress was present in the aorta of old animals (18-24 months), due to a failure in the mechanisms of adaptation to oxidative stress. The observed increase in PGE2 levels in these rats reflected an inflammatory response. All together suggest that vascular oxidative stress and the inflammatory process observed in the old groups of rats could be closely related to vascular aging. Our results also remark the importance of the adaptative response to oxidative stress.

New hematopoietic differentiation antigens detected by anti-K562 monoclonal antibodies.

Following immunizations of BALB/c mice with K562 cells, we have obtained seven original monoclonal antibodies (MoAbs): (a) One MoAb, GA3, defines an antigen essentially restricted to the red cell series. This antigen is expressed on immature erythroblasts but is not detectable on the surface of early and late erythroid progenitors. GA3 MoAb immunoprecipitates a Mr 105,000 glycoprotein on K562 cells. (b) Two MoAbs, 14B6 and 12B1, react with cells of the monocytic series. MoAb 14B6, which also faintly stains platelets, is reactive with immature myeloid cells and the majority of hematopoietic progenitors. The 14B6 antigen has been immunoprecipitated from 12-O-tetradecanoylphorbol-13-acetate treated K562 cells as a Mr 130,000-100,000 protein. Antigen 12B1 is expressed only on cultured monocyte/macrophages and is restricted to a subpopulation of monocytes and to follicular dendritic cells. It is not detected on hematopoietic progenitors. Immunoprecipitation experiments performed on 12-O-tetradecanoylphorbol-13-acetate treated K562 cells revealed a glycoprotein with a molecular weight of 93,000-86,000. (c) Two anti-K562 MoAbs, CF4 and HE10, recognize a myeloid differentiation antigen expressed from the granulomonocytic colony forming unit stage to polymorphonuclear neutrophils. These MoAbs detect an apparently original glycolipid moiety distinct from LeX. (d) Two MoAbs recognize antigens expressed on the granulomonocytic series. 2E1 recognizes the monocyte low affinity Fc receptor (Mr 40,000) and defines a new cluster of myeloid differentiation (CDw32). The antigen is expressed on a small portion of immature hematopoietic progenitors. 8F5 identifies a Mr 95,000 protein which is also present on plasma cells. In some experiments, it is detected on erythroid colony forming unit analysis. Immunizations with K562 cells thus resulted in the production of antibodies recognizing antigens of the monocytic, granulocytic, as well as erythroid series. However, three of them are also detected on hematopoietic progenitors.

Expression of the serglycin gene in human leukemic cell lines.

The expression of the human serglycin gene was determined in nine human leukemic cell lines, representing a spectrum of erythrocytic, megakaryocytic, monocytic, granulocytic, and lymphocytic potentialities. By Northern blot analysis, a 1.4 kb transcript was characterized in some of these cell lines, using a cDNA probe coding for human serglycin. Five of these cell lines, HEL, U-937, HL-60, K-562, and KU-812 were treated with phorbol myristic acetate to induce differentiation. Under these conditions the expression of the serglycin gene was modulated compared to the non-induced cells. HL-60, K-562, and KU-812 were also induced with dimethyl sulfoxide and retinoic acid; variations in serglycin transcript level were also observed. The present investigation establishes, at the nucleic acid level, the ability of various cells mimicking different stages in the developmental pathways of the haemopoietic lineage to synthesize proteoglycans belonging to the serglycin family. The results reported here led us to conclude that serglycin expression is closely associated with the haemopoietic cell differentiation pathway. The putative functions of serglycin in the haemopoietic system are briefly discussed.

Expression of platelet glycoproteins by erythroid blasts in four cases of trisomy 21.

In four patients with trisomy 21 (three constitutional, one acquired) with a morphological undifferentiated leukemia, diagnosis of erythroid leukemia was established by both immunophenotyping and ultrastructural studies. Indeed, a majority of blasts from three patients expressed several erythroid markers such as carbonic anhydrase 1, spectrin beta chain, and glycophorin A. In addition, band 3 and hemoglobin were immunologically detected in a fraction of the blast cells from two cases. At ultrastructural level, a majority or all blast cells exhibited erythroid differentiation features such as theta granules and ferritin molecules. However, platelet glycoproteins GP Ib, GP IIb, and GP IIIa were also immunologically detected in a fraction (from 14-82%) of the blasts. Since the ultrastructural study indicated that some promegakaryoblasts were also present in three patients, double labeling between erythroid markers (glycophorin A or carbonic anhydrase I) and platelet glycoprotein (Ib or IIIa) was performed and showed a clear overlap between the two kinds of markers. A similar approach was performed at ultrastructural level and indicated that blast cells with ultrastructural erythroid features of differentiation may have three distinct phenotypes, i.e., presence of glycophorin A without platelet glycoproteins or, conversely, the presence of platelet glycoproteins without glycophorin A and coexpression of glycophorin A and platelet glycoproteins. Expression of glycophorin A correlated directly with the differentiation level of the erythroid blasts, whereas platelet glycoproteins were essentially expressed in the more primitive leukemic erythroid cells. The GP Ib synthesized by these blasts was subsequently studied. The GP Ib alpha mRNA analyzed by Northern blot from these erythroid cells was identical in size with that from megakaryocytic cells as was the molecular weight of the GP Ib molecule from both after immunoprecipitation by a monoclonal antibody. Therefore, "in vivo" erythroid leukemic cells may express the main platelet glycoproteins including GP Ib.

Ultrastructural and cytochemical characterization of blasts from early erythroblastic leukemias.

Among nine cases of early erythroblastic leukemia previously diagnosed using a panel of antibodies, two patients have erythroid blasts expressing glycophorin A, seven patients have blasts with a more immature phenotype. These immature blasts were labeled by the FA6-152 monoclonal antibody when studied with the immunogold technique. The blasts exhibited large nucleoli, and their cytoplasm contained numerous ribosomes and large mitochondria. In the Golgi apparatus several granules resembled the theta granules as previously described and contained ferritin molecules in the absence of rhopheocytosis. A large proportion of these blasts exhibited a platelet peroxidase (PPO)-like activity. As the blasts from the two other patients with a more mature phenotype and glycophorin A reactivity lacked this PPO, this enzyme seems to be restricted to the more immature cells. Since in these leukemic samples immature erythroid blasts were admixed to promegakaryoblasts, immunogold labeling was also performed with antiplatelet antibodies. This latter population which was labeled with C17, a monoclonal antibody to platelet glycoprotein IIIa, showed strong PPO activity but lacked theta granules and ferritin. In the normal bone marrow enriched by panning for CFU-E (8%) and depleted in progenitors of other lineages, blast cells showing characteristics similar to leukemic erythroid blasts were seen. They exhibited theta granules and ferritin and a proportion of them also had a PPO-like activity. Thus, a PPO reaction is not restricted to the platelet-megakaryocyte line. In conclusion, a PPO-like activity and ferritin molecules were present in immature leukemic erythroid blasts. Similar cells could be identified from normal bone marrow.

Expression of interleukin 6 and its specific receptor by untreated and PMA-stimulated human erythroid and megakaryocytic cell lines.

Different human hematopoietic cell lines were analyzed for the presence of interleukin 6 (IL-6) and IL-6 receptor (IL-6-R). Both IL-6 mRNA and secreted active IL-6 protein were detectable in untreated cell lines with erythroid or megakaryoblastic features (K562, HEL, KU 812, MEG-01, and Dami), but they were not expressed constitutively in other leukemic cell lines (KG1, HL60, and U937). IL-6-R production, studied by the presence of its mRNA and specific binding sites for iodinated recombinant IL-6, was detected in most cell lines except K562, HEL, and Dami. Therefore, only KU 812 and MEG-01 coexpress both IL-6 and IL-6-R. After phorbol ester myristate acetate (PMA) treatment, all the cell lines studied expressed or overexpressed IL-6. In the erythroid K562 cell line, IL-6-R was not detectable before induction, but was promptly expressed after stimulation with PMA, suggesting that some of the new features of K562 cells induced by PMA may be mediated by IL-6. However, neutralizing antibodies against IL-6 did not block either the growth arrest or the loss of the erythroid phenotype induced by PMA. The presence of IL-6 and IL-6-R in erythroid and megakaryocytic leukemic cell lines suggests that their synthesis may occur during normal hematopoietic differentiation.

The Mpl-ligand is involved in the growth-promoting activity of the murine stromal cell line MS-5 on ES cell-derived hematopoiesis.

We investigated the ability of the murine stromal cell line MS-5 to enhance the hematopoietic potential of embryonic stem (ES) cells. The presence of increasing concentrations of MS-5 cells during the differentiation of ES cells into embryoid bodies (EBs) resulted in a positive dose effect on the efficiency of EB development. Moreover, the number of myeloid progenitors derived from EBs at days 6 and 10 of differentiation significantly increased. This increase resulted from an elevation of both the proportions of positive EBs (EBs containing at least one progenitor each) and the progenitor cell content per positive EB. The stimulatory activity of MS-5 cells affected all types of myeloid progenitors except erythroid progenitors, which were depressed. However, the relative numbers of ES-derived granulocyte-macrophage progenitors (colony-forming units granulocyte/macrophage [CFU-GM], -macrophage [CFU-M], and -granulocyte [CFU-G]) and of mixed cell colonies were unchanged. In contrast, the incidence of megakaryocytic progenitors (colony-forming units-megakaryocyte [CFU-MK]) was significantly increased, that of erythroid progenitors (burst-forming units-erythroid [BFU-E]) was concomitantly decreased, and the total numbers of both progenitor types remained constant. Addition of Mpl-ligand (Mpl-L; thrombopoietin) during the growth of EBs was found to mimic the effect of the MS-5 cell line on the output of progenitor cells. No effect of Mpl-L on the efficiency of EB formation was observed. In addition, supplementation of cultures with sufficient soluble Mpl to abrogate Mpl-L activity resulted in the reversion of the quantitative and qualitative effects of MS-5 cells on progenitor cell formation but not on the efficiency of EB formation. Together, these data indicate two major effects and two levels of action of the MS-5 cell line on hematopoietic differentiation of ES cells. First, the cell line acts before hematopoietic determination, promoting the plating efficiency of ES cells via mechanisms that remain to be clarified. Second, at a later stage of differentiation, the MS-5 cells promote hematopoiesis within EBs. Mpl-L appears to be one of the components that confer this latter ability on the MS-5 cell line.

Erroneous results of 3H-thymidine incorporation are related to position of thymidine residues in oligodeoxynucleotides.

Antisense oligodeoxynucleotides (ODNs) targeted to complementary mRNA sequences have proved to be a powerful approach in assessing the function and the role of unique genes in cell proliferation, differentiation, or transformation. Despite their importance in the development of future therapies, little is known about their fate after uptake by cells. Here, we have examined the contribution of individual nucleotide residues from synthetic nonspecific ODNs on assays commonly used to measure cell proliferation. A dramatic decrease of the 3H-thymidine (3H-T) incorporation was obtained with nonspecific ODNs, while no effect on cell proliferation was observed as assessed by three other techniques. We demonstrate that the presence and position of thymidine in the ODNs directly interfere with the intracellular thymidine pool, leading to faulty data of 3H-T incorporation. As an alternative method, we used 3H-deoxyuridine (3H-dU), which is integrated more efficiently in DNA than thymidine. We observed that 3H-dU incorporation was also decreased. In conclusion, caution should be exercised in the interpretation of the results of 3H-T and 3H-dU incorporation in the presence of oligodeoxynucleotides.

Simultaneous generation of nitric oxide and superoxide by inflammatory cells in rats.

It has recently been shown that peroxynitrite anion is a powerful oxidant than can initiate lipid peroxidation. As this oxidant is the product of the reaction between nitric oxide and superoxide, we have studied whether cells isolated from an inflammatory exudate can release both radicals simultaneously under physiological conditions. The carrageenin-induced granuloma model in rats was used. Cells from the inflammatory pouch were stimulated with opsonized zymosan in the absence or in the presence of exogenous L-arginine. Nitric oxide production without exogenous L-arginine was detectable after 15 min (0.29 nmol NO2-) and increased with time (1.65 nmol NO2- at 4 h). When nitrite released from cells was expressed as a rate a burst was shown in the first few minutes. Between 0 and 15 min, cells produced NO2- at the following rates: 20 pmol NO2-/1 x 10(6) cells/min without exogenous L-arginine and 83 pmol NO2-/1 x 10(6) cells/min with exogenous L-arginine. Production was further stimulated with opsonized zymosan (92 pmol NO2-/1 x 10(6) cells/min), and inhibited by L-NMMA and L-NIO. The production of superoxide increased for up to 2 h and then stabilized. A significant increase in nitrite was observed in the presence of SOD, whereas L-NIO increased superoxide generation. These results suggest that peroxynitrite anion may be formed by inflammatory cells.

Different roles for nitrogen monoxide and peroxynitrite in lipid peroxidation induced by activated neutrophils.

We studied the roles of nitrogen monoxide (NO&z.rad;) and peroxynitrite produced by the polymorphonuclear leukocytes (PMNs) isolated from an inflammatory exudate. PMNs were incubated either in a medium with a submicromolar concentration of iron or in a diethylenetriaminepenta-acetic acid (DTPA)-containing medium, and stimulated with phorbol 12-myristate 13-acetate (PMA) to generate free radicals. In both conditions superoxide anion (O(2)(*)(-)), NO&z.rad; and peroxynitrite were produced. In the presence of arachidonic acid, malondialdehyde (MDA) was generated. This MDA was generated in one of two way; the peroxynitrite iron-independent mechanism (40%) and the Fenton reaction, caused by free iron (60%). We also observed that the addition of L-arginine was followed by a 42% reduction in MDA, which can be explained by the antioxidant effect of NO&z.rad;. These results indicate that lipid peroxidation can occur in the absence of iron, through a peroxynitrite-mediated mechanism, and that NO&z.rad; may act as an antioxidant when it is produced in large amounts.

A flavonoid-rich diet increases nitric oxide production in rat aorta.

1. Red wine intake is associated with a low risk of cardiovascular disease. This effect has been partly attributed to the action of polyphenolic compounds, which decrease the oxidation of plasma low density lipoproteins. Moreover, nitric oxide ((*)NO) is a vasodilator and polyphenolic compounds induce endothelium-dependent vasorelaxation in vitro. 2. Here we studied whether a diet rich in dealcoholated red wine (DRW) increases acetylcholine-induced vasorelaxation and whether ingestion of DRW-, quercetin- or catechin-rich diets modifies the (*)NO-cyclic guanosine-3',5'-monophosphate (cyclic GMP) pathway and superoxide anion (O2(.-)) release in aorta in a resting state in rats fed semi-purified diets containing either 35% (v w(-1)) DRW, 0.3% (w w(-1)) quercetin or 0.3% (w w(-1)) catechin for 10 days. 3. (*)NO-mediated vasorelaxation induced by acetylcholine was greater in rats fed the DRW-rich diet than in those that received the control diet. 4. Expression of endothelial (*)NO synthase (eNOS) was similar in the four dietary groups. The aortic rings of rats fed either the DRW-, quercetin-, or catechin-rich diets showed higher NOS activity, (*)NO production and cyclic GMP content than those of rats fed the control diet. No changes were observed in O2(.-) production. 5. In summary, diets rich in either DRW, quercetin or catechin induced endothelium-dependent vasorelaxation in rat aorta in a resting state through the enhancement of (*)NO production, without modifying O2(.-) generation, thus the bioavailability of (*)NO was increased. The increase in the (*)NO-cyclic GMP pathway explains the beneficial effect of flavonoids at vascular level.