Compliance with dietary and nutrient recommendations in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada cohort at recruitment

BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.

Declaraciones nutricionales

Publicado en la página web de la Consejería de Salud y Bienestar social: www.juntadeandalucia.es/salud (Inicio / Profesionales / Salud Pública / Promoción de la Salud)

Increased soluble Fas plasma levels in subjects at high cardiovascular risk - Atorvastatin on inflammatory markers (AIM) study, a substudy of ACTFAST

OBJECTIVE Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment. METHODS AND RESULTS ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk > 20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides < or = 600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL. CONCLUSIONS sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.

Usefulness of Clinical Scores for Patient Risk Stratification in Non-ST Elevation Acute Coronary Syndrome: Any Role for Serum Markers of Inflammation?

Risk stratification of patients with unstable angina or non ST-segment elevation myocardial infarction (UA/NSTEMI) is problematic given the heterogeneous presentation of the condition and clinical characteristics of patients. We sought to compare, in acute coronary syndrome patients, the prognostic value of two frequently used risk scores (RS): the Thrombolysis in Myocardial Infarction (TIMI) and the physician’s risk assessment (PRA). We also assessed whether serum biomarkers can increase the prognostic accuracy of clinical RS.

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)(2)cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway.

Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists.

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis.

INTRODUCTION Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN. METHODS Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data. RESULTS Microthrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome. CONCLUSIONS Microthrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series.

The MRC1/CD68 Ratio Is Positively Associated with Adipose Tissue Lipogenesis and with Muscle Mitochondrial Gene Expression in Humans.

BACKGROUND Alternative macrophages (M2) express the cluster differentiation (CD) 206 (MCR1) at high levels. Decreased M2 in adipose tissue is known to be associated with obesity and inflammation-related metabolic disturbances. Here we aimed to investigate MCR1 relative to CD68 (total macrophages) gene expression in association with adipogenic and mitochondrial genes, which were measured in human visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in rectus abdominis muscle (n = 23). The effects of surgery-induced weight loss were also longitudinally evaluated (n = 6). RESULTS MCR1 and CD68 gene expression levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to total CD68 was present in subjects with less body fat and lower fasting glucose concentrations. The ratio MCR1/CD68was positively associated with IRS1gene expression and with the expression of lipogenic genes such as ACACA, FASN and THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased significantly after the surgery-induced weight loss (+44.7%; p = 0.005) in parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio was significantly associated with muscle mitochondrial gene expression (PPARGC1A, TFAM and MT-CO3). AT CD206 was confirmed by immunohistochemistry to be specific of macrophages, especially abundant in crown-like structures. CONCLUSION A decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial dysfunction at least at the level of expression of adipogenic and mitochondrial genes.

Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.

CONTEXT Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. OBJECTIVE The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURE Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. RESULTS In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. CONCLUSIONS Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.

Bone turnover markers in HIV-infected patients before starting antiretroviral therapy.

Purpose: Bone turnover markers (BTM) - aminoterminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide of type 1 collagen (b-CTX) - are related to bone density and fracture risk. A high prevalence of osteopenia/osteoporosis and hypovitaminosis D has been reported in HIV patients, however there are few data about BTM in this population. Our aim was to analyse the prevalence of elevated serum levels of BTM in HIV patients before starting antiretroviral therapy (ART), and related factors. Methods: Cross-sectional study of a series of HIV-patients who started ART during June/11-June/12 in our hospital. Patients with presence of diseases or treatments known to affect bone metabolism were excluded. Epidemiological, clinical, and immunovirological data in addition to serum fasting levels of glucose, lipid profile, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D3 (25OHD), parathyroid hormone (PTH), P1NP, and β-CTX were collected. Definitions: hypovitaminosis D if 25OHD<30 ng/ml, vitamin D deficiency if 25OHD<20 ng/ml; elevated levels of BTM if β-CTX (ng/ml) >0.64 (men<70 years),>0.85 (men>70 years),>0.58 (pre-menopause women), >0.99 (post-menopause women), or P1NP (ng/mL)>69.4 (men<60 years), >71.1 (men>60 years), >55.7 (pre-menopause women), >61.2 (post-menopause women). Results: 47 patients were included, 91.5% men, median age 37.1 years (30.0-44.3), and 93.6% sexual transmission of HIV (34 HMX, 10 HTX). Median time since the diagnosis of HIV was 3.4 months (1.4- 31.7); there were 7 (14.9%) Aids cases, median CD4 count was 277/ mm3 (155-433), and HIV-VL 4.8 log10 (4.1-5.2). Median serum 25OHD was 29 mg/L (21.9-41.1), with a prevalence of hypovitaminosis of 52.2%, and deficiency of 17.4%. PTH was in range in all cases. Median serum P1NP was 33.3 ng/mL (24.5-52.5) and β-CTX 0.25 ng/mL (0.20-0.45); five (11.4%) patients presented high levels of BTM: 4 men, median age 37.1 years, median CD4 count 247/mm3, median HIV-VL 5.18 log10, and one with hypovitaminosis D. Elevated BTM were related with no clinical, analytical, immunovirological parameters nor with serum levels of 25OHD nor PTH. Conclusions: The prevalence of elevated BTM was high in this series of HIV-patients, mostly young men, with short time of HIV infection and with no immunovirologic control. BTM were related with no clinical nor analytical data.

Evaluation of factors affecting plate waste of inpatients in different healthcare settings.

INTRODUCTION AND AIMS: Satisfaction of inpatients with served food within a hospital care system still constitutes one of the main attempts to modernize food services. The impact of type of menu, food category, hospital centre and timetable on the meals wastage produced in different Spanish healthcare settings, was evaluated. METHODS: Meal wastage was measured through a semiquantitative 5-point scale ("nothing on plate"; "¼ on plate"; "half on plate"; "¾ on plate" and "all on plate"). The study was carried out in two periods of three months each in 2010 and 2011. A trained person took charge of measuring plate waste classified into 726 servings belonging to 11 menus. In total 31,392 plates were served to 7,868 inpatients. A Kruskal-Wallis non-parametric test (p < 0.05) was applied to evaluate significant differences among the variables studied. RESULTS: The menus were satisfactorily consumed because more than 50% of the plates were classified as "nothing on plate". Regarding food categories, 26.78% of the plates corresponded to soups and purées, while pasta and rice, and prepared foods were only distributed in 4-5% of the servings. Desserts were mostly consumed, while cooked vegetables were less accepted by the inpatients evaluated. Other factors such as hospital centre influenced plate waste (p < 0.05) but timetable did not (p > 0.05). CONCLUSION: Visual inspections of plate waste might be useful to optimize type and quality of menus served. The type of menu served and the food category could have a great influence on food acceptability by the inpatientsstudied.

Cocoa polyphenols and inflammatory markers of cardiovascular disease.

Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review.