Implication of non-coding PAX6 mutations in aniridia.

There is an increasing implication of non-coding regions in pathological processes of genetic origin. This is partly due to the emergence of sophisticated techniques that have transformed research into gene expression by allowing a more global understanding of the genome, both at the genomic, epigenomic and chromatin levels. Here, we implemented the analysis of PAX6, whose coding loss-of-function variants are mainly implied in aniridia, by studying its non-coding regions (untranslated regions, introns and cis-regulatory sequences). In particular, we have taken advantage of the development of high-throughput approaches to screen the upstream and downstream regulatory regions of PAX6 in 47 aniridia patients without identified mutation in the coding sequence. This was made possible through the use of custom targeted resequencing and/or CGH array to analyze the entire PAX6 locus on 11p13. We found candidate variants in 30 of the 47 patients. 9/30 correspond to the well-known described 3' deletions encompassing SIMO and other enhancer elements. In addition, we identified numerous different variants in various non-coding regions, in particular untranslated regions. Among these latter, most of them demonstrated an in vitro functional effect using a minigene strategy, and 12/21 are thus considered as causative mutations or very likely to explain the phenotypes. This new analysis strategy brings molecular diagnosis to more than 90% of our aniridia patients. This study revealed an outstanding mutation pattern in non-coding PAX6 regions confirming that PAX6 remains the major gene for aniridia.

Trastorno por Déficit de Atención e Hiperactividad (TDAH), ¿se mantiene el diagnóstico de sospecha realizado en Atención Primaria en la Unidad de Salud Mental InfantoJuvenil? / Attention deficit / hyperactivity disorder (ADHD), Is the presumptive diagnosis carried out in Paediatric Primary Care maintained in Child and Adolescent Mental Health Unit?

INTRODUCCIÓN: El TDAH es uno de los trastornos del neurodesarrollo más frecuentes. Los pediatras de Atención Primaria (AP) reciben a menudo pacientes que presentan síntomas cardinales de esta entidad. OBJETIVOS: Analizar la concordancia entre la sospecha diagnóstica realizada en AP y el diagnóstico emitido en la Unidad de Salud Mental Infanto-Juvenil (USMIJ). MATERIAL Y MÉTODOS: Estudio observacional descriptivo prospectivo en el que se reclutaron 374 pacientes menores de 16 años, derivados a la USMIJ del área sanitaria de Pontevedra durante el año 2016. Se analizó el índice Kappa global y específico para los diferentes diagnósticos. RESULTADOS: De los 374 pacientes, 233 fueron remitidos con sospecha de TDAH, confirmándose el diagnóstico en 102 pacientes. El índice kappa global de concordancia es de 0.29. En general para la mayoría de los diagnósticos la concordancia fue débil. La concordancia fue buena para el Trastorno del espectro autista (0.61) y muy buena para el Trastorno de conducta alimentaria (1.00). En relación al TDAH, la sensibilidad fue del 95.33% (índice de confianza (IC) 95% 90.86-99.79), la especificidad del 50.94% (IC95% 44.75-57.12), valor predictivo positivo del 43.78% (IC95% 37.19-50.36), y valor predictivo negativo del 96.45% (IC95% 93.05-99.86). CONCLUSIONES: La concordancia obtenida entre AP y la USMIJ es baja en nuestra área sanitaria. La correlación diagnóstica medida con el índice kappa es débil para el TDAH, sin embargo, es buena tanto para el diagnóstico del Trastorno del espectro autista como para los trastornos de conducta alimentaria. La validez diagnóstica para TDAH es moderada, con una sensibilidad alta y una especificidad baja

INTRODUCTION: ADHD is one of the most common neurodevelopmental disorders. Primary care (PC) pediatricians often receive patients who show cardinal symptoms of this entity. OBJECTIVE: To analyze the concordance between the presumptive diagnosis performed in PC and the definitive diagnosis of the Child and Adolescent Mental Health Unit (CAMHU). MATERIALS AND METHODS: Prospective descriptive observational study in which 374 patients under 16 years were recruited from the CAMHU of Pontevedra health area during 2016. The Kappa index was analyzed globally and specific for the different diagnoses. RESULTS: 374 patients were included, 233 were referred with suspected ADHD, confirming the diagnosis in 102 patients. The global kappa concordance index is 0.29. For most diagnoses, agreement was weak. Concordance was good for Autism (0.61) and very good for Eating Disorder (1.00). For ADHD, the sensitivity was 95.33% (95% confidence interval (CI) 90.86-99.79), specificity 50.94% (CI95% 44.75-57.12), positive predictive value 43.78% (CI95% 37.19-50.36) and negative predictive value 96.45% (95% CI 93.05-99.86). CONCLUSIONS: The concordance obtained between PC and CAMHU is low in our health area. The diagnostic concordace measured with the kappa index is weak for ADHD, however, it is good for both autism and eating disorders. The diagnostic validity for ADHD is moderate, with a high sensitivity and low specificity

Preliminary study: fibre content in pet rabbit diets, crude fibre versus total dietary fibre.

Fibre is an important nutrient for rabbit health, and, on commercial pet rabbit packaging, it is labelled as crude fibre (CF). In several species, it is considered that CF is not an accurate representation of the fibre content in feedstuffs. The objective of this study was to compare the CF stated on the label (CFL) with laboratory analysis of CF (CFA) and the analysed content of total dietary fibre (TDF) in different commercial pet rabbit feeds. We selected 15 commercial diets and analysed CF and TDF. A mixed model was used to evaluate differences between CFL, CFA and TDF, and linear regression was performed to study the correlation between CFL and CFA with TDF. CFA and CFL were not significantly different (p = 0.836) in the feeds studied, and both were lower than TDF (p < 0.001). The correlations between TDF and both CFA and CFL were significant (p < 0.001 and p = 0.02, respectively), but the correlation was better with CFA (R = 0.86) than with CFL (R = 0.53). As expected, TDF content was higher than CF content, an average of two times. These results suggest that the CF content in rabbit diets reported on the label is not an appropriate indicator of their total fibre content, although further work with a larger sample size is required to confirm these results.

Evaluation of the use of esterified fatty acid oils enriched in medium-chain fatty acids in weight loss diets for dogs.

Esterified fatty acid oils (EAOs) are obtained from esterification of vegetable acid oils with glycerol. These fat sources have the same fatty acid (FA) composition as their respective native oils but new chemical properties. Several studies have confirmed the potential of medium-chain fatty acids (MCFA) to reduce fat mass (FM) in humans and rodents. This study investigates the use of EAOs with different MCFA proportions on food preferences, digestibility and weight loss management in dogs. A basal diet was supplemented with 8% of three different fat sources: C0: soya bean-canola EAO, C20: soya bean-canola (80%) coconut (20%) EAO and C40: soya bean-canola (60%) coconut (40%) EAO. Food preference of these EAOs was tested using a two-pan preference test. Dogs presented a higher daily food intake of C20 and C40 compared to C0 (C20: 155 ± 18.6 g vs. C0: 17 ± 7.0 g, p < 0.001; C40: 117 ± 13.9 g vs. C0: 28 ± 10.5 g, p < 0.05 respectively). Also, the digestibility of the three experimental diets was tested. C20 and C40 showed higher ether extract, total FA and saturated FA digestibilities (p < 0.05) than C0 diet. Lastly, the three diets were investigated in a 14-week weight loss study, following 16 weeks of ad libitum feeding to induce overweight condition. Body weight (BW) reduction was lower (C0: 20.1 ± 2.32%, C20: 14.6 ± 1.43% and C40: 15.7 ± 1.23%, p < 0.05) and FM was higher (FM, 18.7 ± 3.42%, 27.9 ± 3.90% and 28.2 ± 2.88% for C0, C20 and C40, respectively, p < 0.05) for diets C20 and C40 than for C0. Feeding diets with MCFA at these inclusion levels to experimentally overweight dogs during 14 weeks do not result in faster weight loss compared to unsaturated long-chain FA.

Viral and inflammatory markers in cerebrospinal fluid of patients with HIV-1-associated neurocognitive impairment during antiretroviral treatment switch.

OBJECTIVES: The aim of the study was to evaluate HIV-1 viral load (VL) and inflammatory markers in cerebrospinal fluid (CSF) and neurocognitive performance in patients with neurocognitive impairment (NCI) while they were receiving tenofovir (TDF)/ emtricitabine (FTC)/efavirenz (EFV) and after switching to a regimen with enhanced central nervous system (CNS) penetrability. METHODS: This was a prospective, single-arm pilot study. HIV-1-infected patients with plasma viral suppression and HIV-associated NCI on a regimen including TDF/FTC/EFV were switched to abacavir (ABC)/lamivudine (3TC)/maraviroc (MVC). The Global Deficit Score (GDS) was used to score cognitive function at baseline and 48 weeks after treatment switch. Both CSF and blood samples were taken at baseline and between weeks 24 and 36 after switching. HIV-1 RNA in plasma and CSF was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Inflammatory biomarkers in CSF were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 71 patients receiving TDF/FTC/EFV were screened. Twelve of them (17%) had documented NCI, lacked the human leucocyte antigen (HLA)-B*57:01 haplotype and harboured Chemokine Receptor Type-5 (CCR5)-tropic virus. Eight patients had detectable HIV-1 RNA (between 2.7 and 41.6 HIV-1 RNA copies/mL) in CSF at baseline. All participants had elevated levels of neopterin and Monocyte Chemoattractant Protein 1 (MCP-1) in CSF at baseline. Eight out of 12 patients completed their follow-up assessment after treatment switch. The GDS decreased from 0.55 to 0.4 (P = 0.085). Median HIV-1 RNA in CSF decreased from 3.49 to 2.20 (P = 0.23). Among the inflammation markers in CSF, tumour necrosis factor (TNF)-α decreased significantly from median 0.51 to 0.35 pg/mL (P = 0.027), showing a correlation with the changes in neopterin, interferon (IFN)-γ and interleukin (IL)-6. CONCLUSIONS: Most patients with NCI receiving TDF/FTC/EFV had low-level viraemia and/or increased inflammatory markers in CSF. Treatment switching to an MVC-containing regimen with better CNS penetration resulted in a trend towards improvement in neurocognitive status and reduced TNF-α concentrations in CSF.

Comparison of postprandial lipaemia between native and palm random esterified acid oils in two different monogastric species (dogs and broiler chickens).

It has been reported that applying a chemical reesterification process to a native fat results in a new fat source with different physicochemical properties due to their different fatty acid (FA) positional distribution within the glycerol moiety and their different proportions of mono (MAG)-, di (DAG)- and triacylglycerides (TAG). Thus, this reesterification could affect fat digestion, absorption and metabolism; and this effect could vary among species given their differences in fat metabolism. The aim of this study was to compare the effect of feeding two different random esterified acid oils (REAO), presenting different MAG, DAG and TAG proportions, with their corresponding native oil on postprandial lipaemia in broiler chickens and dogs. For this purpose, 18 dogs and 54 broiler chickens were fed a basal diet supplemented with palm native oil, palm REAO low MAG or palm REAO high MAG. The inclusion level of the oils was 10% of the diet in dogs and 6% in broiler chickens. Serum postprandial TAG concentration (mg/dl) after feeding a single meal was measured at different time points during 12 h in dogs and 3 h in chickens. Although fasting serum TAG concentration values were similar for both species (47 ± 2.4 mg/dl for dogs and 44 ± 3.0 mg/dl for broilers; p = 0.522), postprandial TAG concentrations tended to be higher in broilers than in dogs (p = 0.058). Treatment had no effect on TAG concentration at any time point in any species (p = 0.768 for dogs, p = 0.947 for broilers). However, the postprandial TAG curves were very different between species; in broiler chickens, TAG concentration returned to the fasting values 3 h after feeding while in dogs, the TAG concentration still had not returned to basal levels 12 h after feeding.

Multifunctional targets of dietary polyphenols in disease: a case for the chemokine network and energy metabolism.

Chronic, non-acute inflammation is behind conditions that represent most of the disease burden in humans and is clearly linked to immune and metabolic mechanisms. The convergence of pathways involving the immune response, oxidative stress, increased circulating lipids and aberrant insulin signaling results in CCL2-associated macrophage recruitment and altered energy metabolism. The CCL2/CCR2 pathway and the energy sensor AMP-activated protein kinase (AMPK) are attractive therapeutic targets as a part of preventive management of disease. Several effects of polyphenols are useful in this scenario, including a reduction in the activities of cytokines and modulation of cellular metabolism through histone deacetylase inhibitors, AMPK activators, calorie-restriction mimetics or epigenetic regulators. Research is currently underway to develop orally active drugs with these effects, but it is convenient to examine more closely what we are eating. If a lack of relevance in terms of toxicity and substantial effectiveness are confirmed, plant-derived components may provide useful druggable components and dietary supplements. We consider therapeutic actions as a combination of synergistic and/or antagonistic interactions in a multi-target strategy. Hence, improvement in food through enrichment with polyphenols with demonstrated activity may represent a major advance in the design of diets with both industrial and sanitary value.

Metformin: a cheap and well-tolerated drug that provides benefits for viral infections.

OBJECTIVES: Insulin resistance in viral infections is common. We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process. METHODS: HIV-infected patients (n = 385) were compared with controls recruited from the general population (n = 300) with respect to the genotype distribution of the ATM rs11212617 variant and its influence on selected metabolic and inflammatory variables. We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients. RESULTS: Among the HIV-infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections were frequent. Selected metabolic and/or inflammatory variables were significantly altered in infected patients. Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin. The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07-1.39; P = 0.005). There were no differences between treated and untreated patients in viral loads or variables measuring immune defence, indicating that toxicity is unlikely. CONCLUSIONS: We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients.

Impact of antiretroviral therapy interruption on plasma biomarkers of cardiovascular risk and lipids: 144-week final data from the STOPAR study.

OBJECTIVE: The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study. METHODS: This was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay. Total cholesterol (total-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined using standard methods. RESULTS: Fifty-four patients were included in the study [34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm]. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP-1, which was higher in the TC arm (P = 0.039). MCP-1 and sVCAM-1 were increased relative to baseline at the three study time-points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P = 0.02). t-PA was increased in both arms at the three time-points. Total-c, HDL-c and low-density lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time-points, with no changes in the total-c/HDL-c ratio. HIV viral load positively correlated with MCP-1 at months 12 and 24. Regression analysis showed a significant negative association of HDL-c with MCP-1 and sVCAM-1. CONCLUSIONS: A significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.

Effects of 7-weeks competitive training period on physiological and mental condition of top level judoists.

AIM: We examined hormonal and haematological parameters and the profile of mood states (POMS) in top level judoists undertaking a 7-week competitive training period in a real contest. METHODS: Participants were 10 top level judoists belonging to the Spanish National Team. Training load was calculated by multiplying the training session intensity by the duration of the training session. The judoists competed in two official events on weeks 3 and 6 of the study. RESULTS: Urinary catecholamines increased at the end of the competitive period. Serum cortisol increased during the weeks in which judoists competed, confirming the existence of and anticipatory cortisol response to exercise; although we failed to find serum testosterone increases. Because of leukocyte values did not change, except monocytes, we speculate that the intensity of training was not sufficiently high to evoke injury to muscle tissue. Anger, tension, and fatigue increased according with training load, suggesting that the training exercise led participants into a negative psychological state. CONCLUSION: Findings indicate that during competitive periods, judoists suffer hormonal and mood changes according to training load and competitive events. Results support the usefulness of monitoring biological and psychological markers during season in order to adjust training loads and periods of recovery.

The role of combined assessment of defense against oxidative stress and inflammation in the evaluation of peripheral arterial disease.

Atherosclerosis in symptomatic peripheral arterial disease affects wide portions of numerous arteries in lower extremities. The resulting active inflammation in a considerable amount of arterial tissue facilitates systemic detection via measurement of inflammation-related variables. We reasoned that the combined assessment of defense against oxidative stress, in the form of paraoxonase-1 (PON1), and monocyte migration measured as circulating (C-C motif) ligand 2 (CCL2), may play a role in the evaluation of these patients. Plasma CCL2 and serum PON1-related variables, assessed by their interaction with functional genetic variants, were measured in a cross-sectional study in patients with symptomatic PAD. We found that PON1 activity and concentration were significantly lower and CCL2 concentration higher in PAD patients compared to controls, that the combination of plasma CCL2 and PON1- related values, especially PON1 concentration differentiated, almost perfectly, controls from patients and that the expression of CCL2 and PON1 generally co-localized in the atherosclerotic lesion. Since no association with genetic variants was found, such a relationship is probably the result of the disease. Our data suggest a coordinated role between CCL2 and PON1 that may be detected in blood with simple measurements and may represent an indicator of the extent of atherosclerosis.

Continuous administration of polyphenols from aqueous rooibos (Aspalathus linearis) extract ameliorates dietary-induced metabolic disturbances in hyperlipidemic mice.

The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations. Additionally, we found changes in adipocyte size and number as well as complete prevention of dietary-induced hepatic steatosis. These effects were not related to changes in insulin resistance. Among other possible mechanisms, we present data indicating that the activation of AMP-activated protein kinase (AMPK) and the resulting regulation of cellular energy homeostasis may play a significant role in these effects of rooibos extract. Our findings suggest that adding polyphenols to the daily diet is likely to help in the overall management of metabolic diseases.

Influence of a high-protein diet on energy balance in obese cats allowed ad libitum access to food.

The influence of a high-protein [HP, 47% of metabolizable energy (ME)] diet on energy balance was evaluated in obese cats allowed ad libitum access to food. Energy intake, body weight, body composition, energy expenditure, and concentrations of hormones and metabolites associated with carbohydrate and lipid metabolism (glucose, insulin, free fatty acids, triglycerides and leptin) were measured in cats after consuming either a moderate protein (MP, 27% of ME) or HP diet for 4 months. Indirect respiration calorimetry showed that resting and total energy expenditure (kJ/day) adjusted for either body weight or lean body mass was increased in cats consuming the HP in relation to MP diets. However, voluntary energy intake also was increased in the HP treatment and, thus, there was no difference in body weight between animals consuming the two diets. Body composition measurements using deuterium oxide dilution showed that dietary protein content did not alter amounts of either lean body mass or fat mass. No significant differences (p > 0.05) were observed between the two treatment groups for blood glucose, free fatty acid or leptin concentrations, although there was a trend (p = 0.054) towards an increase of serum insulin concentrations in the cats eating the HP diet. This study showed that short-term ad libitum feeding of an HP diet did not reduce food intake or promote weight loss in obese cats. However, energy expenditure was increased in the HP diet group and it is possible that this effect of HP might help promote weight loss when energy intake is restricted.

Pitfalls in measuring high-density lipoprotein cholesterol concentrations in HIV-infected patients.

OBJECTIVES: HIV infection and its treatment are associated with dyslipidaemia and increased risk of cardiovascular disease. Accurate high-density lipoprotein (HDL) cholesterol values are necessary for the management of these abnormalities, but current methods have not been properly assessed in these patients. The aim of this study was to assess in HIV-infected patients the consistency and accuracy of a synthetic polymer/detergent homogeneous assay used to measure HDL cholesterol concentrations and to evaluate the impact of storage. METHODS: HDL cholesterol was measured using a synthetic polymer/detergent homogeneous method in samples from HIV-infected patients and healthy subjects for each of the storage regimens: baseline, after 1 week at 4 degrees C, and after 12 months at -80 degrees C. The ultracentrifugation and precipitation assays were used for comparison. RESULTS: Three out of every 20 samples from HIV-infected patients had discrepant HDL cholesterol values with respect to the ultracentrifugation method. Overestimation was associated with high C-reactive protein concentrations and underestimation with plasma gamma-globulin concentrations, an effect that was amplified by any of the storage conditions tested. CONCLUSIONS: Caution is needed when using the synthetic polymer/detergent homogeneous method for direct measurement of HDL cholesterol concentrations in HIV-infected patients. This assay is of limited use in clinical trials in which frozen samples are analysed.

Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV-infected patients: relationships with serum markers of oxidation and inflammation.

OBJECTIVES: HIV-infected patients show an increased cardiovascular disease (CVD) risk resulting, essentially, from metabolic disturbances related to chronic infection and antiretroviral treatments. The aims of this study were: (1) to evaluate the agreement between the CVD risk estimated using the Framingham risk score (FRS) and the observed presence of subclinical atherosclerosis in HIV-infected patients; (2) to investigate the relationships between CVD and plasma biomarkers of oxidation and inflammation. METHODS: Atherosclerosis was evaluated in 187 HIV-infected patients by measuring the carotid intima-media thickness (CIMT). CVD risk was estimated using the FRS. We also measured the circulating levels of interleukin-6, monocyte chemoattractant protein-1 (MCP-1) and oxidized low-density lipoprotein (LDL), and paraoxonase-1 activity and concentration. RESULTS: There was a weak, albeit statistically significant, agreement between FRS and CIMT (kappa=0.229, P<0.001). A high proportion of patients with an estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a multivariate analysis, the presence of subclinical atherosclerosis in this subgroup of patients was associated with age [odds ratio (OR) 1.285; 95% confidence interval (CI) 1.084-1.524; P=0.004], body mass index (OR 0.799; 95% CI 0.642-0.994; P=0.044), MCP-1 (OR 1.027; 95% CI 1.004-1.050; P=0.020) and oxidized LDL (OR 1.026; 95% CI 1.001-1.051; P=0.041). CONCLUSION: FRS underestimated the presence of subclinical atherosclerosis in HIV-infected patients. The increased CVD risk was related, in part, to the chronic oxidative stress and inflammatory status associated with this patient population.

The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans.

Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity.