Conceição Calhau

University of Porto, Oporto, Porto, Portugal

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Publications (92)265.34 Total impact

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    ABSTRACT: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health.
    Environmental research. 06/2014; 133C:170-177.
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    ABSTRACT: Anthocyanins are naturally occurring compounds abundant in the human diet. Evidence has accumulated regarding the positive association of their intake with healthy biological effects. The microbiota has just been started to be considered as a metabolic organ, hence contributing to the metabolism of phenolic compounds and, consequently, to their bioavailability and the biological effects displayed by them. This review aimed to compile information regarding interaction of anthocyanins with the microbiota, from two perspectives: (i) identification of their colonic metabolites as potential bioactive molecules and (ii) their role as prebiotic agents. These perspectives are key points in anthocyanin metabolomics. Several metabolites have been identified after anthocyanin consumption with potential health benefits, in particular phenolic acids and simple phenols. On the other hand, microbiota modulation is closely related to several physiological impairments, and its modulation has been considered as a possible mechanism by which phenolic compounds may exert their effect.
    Journal of agricultural and food chemistry. 06/2014;
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    Obesity Surgery 05/2014; 24(5). · 3.10 Impact Factor
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    ABSTRACT: Metabolic syndrome (MetS) clusters the most dangerous cardiovascular disease risk factors. Although insulin resistance and central obesity play an important role in the pathogenesis, the factors that determine its development and ultimate remission after Roux-en-Y gastric bypass (RYGB) are not fully understood. We recruited a prospective cohort of 210 consecutive patients after RYGB between January 2010 and December 2011. Patients were evaluated clinically and with a biochemical profile preoperatively and at 12 months after surgery. Visceral adipose tissue and subcutaneous abdominal adipose tissue samples were collected at surgical intervention. We aimed to identify factors associated with MetS in morbidly obese patients and predictors of its remission 12 months after RYGB. Increasing age (>40 years), male sex, alanine aminotransferase levels and visceral adipose tissue/subcutaneous adipocyte size ratio were independently related to the expression of MetS at the moment of surgery.One year after RYGB, there was a significant decrease in the prevalence of MetS (63.3%-10%; P < 0.001) and in each of its components. A multivariable analysis for the remission of MetS identified that only fasting glucose levels (OR = 13.4; P = 0.01) and duration of obesity (OR = 1.08; P = 0.04) were independently related to the persistence of MetS. A metabolic score (scale of 1-10), consisting of duration of obesity, fasting blood glucose levels, the presence of high blood pressure and low levels of high-density lipoprotein identified 4 different risk categories for the persistence of MetS (area under the curve = 0.848). The metabolic score can be used to predict the remission of MetS after RYGB with high accuracy. Patients in high-risk groups might be managed more aggressively and low-risk patients may have their medication discontinued earlier with extra safety.
    Annals of surgery 04/2014; · 7.90 Impact Factor
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    ABSTRACT: This study aimed to evaluate the transmembrane transport of different flavonoids (flavan-3-ols, anthocyanins and flavonols) and some of their metabolites (methylated and conjugated with glucuronic acid) across hCMEC/D3 cells (a blood-brain barrier (BBB) model). Further metabolism of the tested compounds was assayed and their transport modulated in an attempt to elucidate the mechanisms behind this process. The transport across hCMEC/D3 cells was monitored in basolateral media at 1, 3 and 18h by HPLC-DAD/MS. All the flavonoids and their metabolites were transported across hCMEC/D3 cells in a time-dependent manner. In general, the metabolites showed higher transport efficiency than the native flavonoid. No further biotransformation of the metabolites was found as consequence of cellular metabolism. Anthocyanins and their metabolites crossed this BBB cell model in a lipophilicity-dependent way. Quercetin transport was influenced by phosphatase modulators, suggesting a phosphorylation/dephosphorylation regulation mechanism. Overall, this work suggests that flavonoids are capable of crossing the BBB and reaching the central nervous system.
    Food Chemistry 04/2014; 149:190-6. · 3.33 Impact Factor
  • Obesity Surgery 03/2014; · 3.10 Impact Factor
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    ABSTRACT: Anthocyanins are naturally occurring compounds widespread in plant-derived foodstuffs and therefore abundant in human diet. There are evidences regarding the positive association of their intake with healthy biological effects displayed in vivo. This review aims to highlight some aspects regarding anthocyanins bioavailability; these include a short introductory part of anthocyanin chemistry, stability, occurrence and intake. This first part is followed by a more detailed one concerning the main topic of the review that includes the bioavailability and metabolism of anthocyanins. Special attention is given to the contribution of the gastric mucosa to anthocyanin absorption as the result of the high content of intact anthocyanins (20–25%) detected is plasma few minutes after intake. The contribution of intestinal tissue and the microbiota impact in anthocyanin absorption and bioactivity is also highlighted. Despite the biological activities that have been associated with these compounds, anthocyanins appear to be rapidly absorbed and eliminated, reaching only low maximal concentrations in plasma and urine. Some possible critical factors that may contribute to this paradox were also explored including the ability of a compound to cross membranes, the effect of pH, digestive enzymes, biliary acids and microbiota, the lack of sensitivity of the analytical method, the possible ingestion of pigments (anthocyanin derivatives, especially in the case of red wine) and the influence of the food matrix. Generally, the bioavailability of anthocyanins is presumed but whether the effect is due to the native compounds or other forms, which mechanism are involved or which factors have crucial impact on bioavailability still remain underexplored.
    Journal of Functional Foods 03/2014; 7:54–66. · 2.63 Impact Factor
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    ABSTRACT: Diet has gained scientific community attention due to the crucial role in health maintenance, but also in disease treatment, and essential in disease prevention. Several food and food components, particularly phenolic rich foods, have been investigated as they present themselves as putative functional foods. In the past decades, obesity has reached epidemic proportions and consequently, metabolic syndrome (a set of disorders as impaired glucose tolerance, insulin resistance, abdominal obesity, dyslipidemia and high blood pressure, which increase the risk of cardiovascular disease and diabetes) incidence is increasing worldwide at an alarming rate and this phenolic rich foods, specially berries have been investigated to their potential beneficial effect in this disorders. In the present work the chemistry of blueberries (BB) (fruits of some Vaccinium species) was summarised as well as the knowledge about bioavailability and biokinetic of anthocyanins from blueberries with particular emphasis on its implications in metabolic disorders.
    Journal of Functional Foods 10/2013; 5(4):1518–1528. · 2.63 Impact Factor
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    ABSTRACT: The blood-brain barrier (BBB) plays a key role in limiting and regulating glucose access to glial and neuronal cells. In this work glucose uptake on a human BBB cell model (the hCMEC/D3 cell line) was characterized. The influence of some hormones and diet components on glucose uptake was also studied. (3)H-2-deoxy-D-glucose ([(3)H]-DG) uptake for hCMEC/D3 cells was evaluated in the presence or absence of tested compounds. [(3)H]-DG uptake was sodium- and energy-independent. [(3)H]-DG uptake was regulated by Ca(2+) and calmodulin but not by MAPK kinase pathways. PKC, PKA and protein tyrosine kinase also seem to be involved in glucose uptake modulation. Progesterone and estrone were found to decrease (3)H-DG uptake. Catechin and epicatechin did not have any effect, but their methylated metabolites increased [(3)H]-DG uptake. Quercetin and myricetin decreased [(3)H]-DG uptake, and glucuronic acid-conjugated quercetin did not have any effect. These cells expressed GLUT1, GLUT3 and SGLT1 mRNA.
    Journal of Membrane Biology 08/2013; · 2.48 Impact Factor
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    ABSTRACT: Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and (3)H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. (3)H-Deoxyglucose ((3)H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and (3)H-thymidine incorporation (P < 0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal (3)H-DG uptake by adipocytes (P < 0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of (3)H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX.
    Cell Biology and Toxicology 08/2013; · 2.34 Impact Factor
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    ABSTRACT: Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), and its metabolites p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyldichloroethane (p,p'-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p'-DDT, p,p'-DDE, and p,p'-DDD (50-1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
    Environmental Toxicology 08/2013; · 2.71 Impact Factor
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    ABSTRACT: Persistent organic pollutants are both persistent and bioaccumulative, manly in the adipose tissue (AT), and have the potential to induce adverse effects on human health, namely in metabolic syndrome. According to our human biomonitoring studies and the evidences exposed in the literature, p,p'-DDE appear as an important compound with the ability to act as an endocrine disruptors and an epigenetic modulator. Twenty-four male Wistar rats were exposed during 12 weeks to p,p'-DDE in water (100 µg/kg/day -2.5 times less than LOAEL), with or without an high-fat diet, and evaluated the effects on metabolism and adipose tissue biology. The animals were randomly divided into four treatment groups: standard (St); high-fat (HF); standard with DDE (St/DDE); high-fat with DDE (HF/DDE). Briefly, despite HF/DDE did not induce a higher increase of body weight compared to the HF group, a metabolic dysfunction effect was observed, namely by exacerbating some of the several metabolic syndrome accompanying features, such as elevated fasting glucose, glucose intolerance and hypertension. Focusing on AT effects, a transcriptome analysis comparing the two HF groups revealed a change in approximately 600 genes after DDE exposure. Among those transcription changes are the increase of DPP4 and decrease of the neuropeptide galanin, this last also presenting changes in the pattern of methylation in its promoter region. Our results confirm that DDE exposure appears to have an important effect in metabolic syndrome evolution per se, worsening the metabolic impact of a HF diet exposure. Curious changes in AT transcriptome, namely in key metabolism-related genes, in some cases also revealing changes in epigenetic regulation, advance possible mechanisms of action for these DDE exposure effects which deserve further investigation. This work was supported by FCT (Fundo Social Europeu, Programa Operacional Potencial Humano da EU (POPH); PEst-OE/SAU/UI0038/2011; SFRH/BD/46640/2008, SFRH/BD/64691/2009, SFRH/BD/78367/2011, SFRH/BD/47200/2008, SFRH/BPD/75294/2010; and SFRH/BPD/40110/2007).
    Environmental Health 2013, Boston; 03/2013
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    ABSTRACT: There are extended evidences associating persistent organic pollutants (POPs) and obesity aetiology, as well as other metabolic abnormalities. Due to their lipophilic nature, they tend to accumulate in adipose tissue (AT), where they can have the potential to induce adverse effects on human health. In this regard, we aimed to evaluate their presence in human AT (visceral, vAT and subcutaneous, scAT), especially in a sample of obese patients subjected to bariatric surgery and subsequently asses its putative association with metabolic parameters. To address this issue, AT samples (vAT and scAT; n=189) from Portuguese obese patients (body mass index, BMI > 40) were collected during surgery and the levels of 14 POPs were determined by GC-ECD. Anthropometric and biochemical data were collected, both before and 6 months after surgery and measurement of adipocyte size was performed in AT samples. Our data confirms that POPs are pervasive in this obese population, their abundance increasing with age and with the duration of obesity. We observed a dissimilar POP storage capability of the two AT depots and a positive correlation between POP levels and metabolic abnormalities, namely with glycaemia and hypertension, both components of the metabolic syndrome. Finally, POP levels seem to be a predictor of unsuccessful weight loss in obese patients. These results underline the importance of POPs' influence on human development of metabolic abnormalities, even when considering an obese population. This awareness of these POPs effects in human samples is fundamental to prompt the action of public health authorities in order to limit the extent of human exposure to environmental contaminants and prevent their health effects. This work was supported by FCT (Fundo Social Europeu, Programa Operacional Potencial Humano da EU (POPH); PEst-OE/SAU/UI0038/2011; SFRH/BD/46640/2008, SFRH/BD/47200/2008, SFRH/BD/64691/2009, SFRH/BD/78367/2011, SFRH/BPD/75294/2010; and SFRH/BPD/40110/2007) and Projectos de Investigação na Pré-graduação 2010, Universidade do Porto-150.
    Environmental Health 2013, Boston; 03/2013
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    ABSTRACT: Background Preoperative prediction of weight loss after Roux-en-Y gastric bypass (RYGB) could help surgeons in managing surgical lists and patients’ expectations. Objective Understand if preoperative metabolic control might improve surgical results. Setting Academic medical center Methods Prospective cohort of 163 consecutive patients that underwent RYGB with at least 1 year of follow-up. Results Most patients were female (90.2%), with a mean age of 38 (19-60) and a BMI of 46.0(34.3-59.9) kg/m2. After 12 months, the mean Body Mass Index (BMI) was 29.7 kg/m2 (21.5 – 39.9) with a corresponding percentage of excess weight lost (%EWL) of 78.8% and a percentage of weight loss (%WL) of 35.1%. Patients with the highest preoperative fasting blood glucose (FBG) were older (42 vs. 36;p<.001); were more likely to have Type 2 Diabetes [(T2DM), (40% vs. 6.8%;p<.001)] and Metabolic Syndrome (89% vs. 25%;p<.001), had a slightly higher BMI (30.8 vs. 29.3 kg/m2;p=.03) and achieved a significantly lower percentage of EWL and WL at 12 months (72.5% vs. 81.2%;p=.004; 33.2 vs. 35.9%;p=.03, respectively). We observed a dose-response effect with increasing FBG (<85mg/dL; [85 – 100]mg/dL; ≥ 100mg/dL), respectively, with 83.5%; 80.0% and 72.5%(p=.009) of %EWL at 12 months. By multivariate logistic regression, initial BMI and FBG>100, were the only variables related (inversely) with the probability of achieving a %EWL>80 or % WL>35. This effect was not detected in patients receiving oral anti-diabetic medications. Conclusion Higher pre-operative FBG is independently related to a poorer weight loss 12 months after RYGB; this suggests, the need to offer earlier surgical intervention for severely obese patients with impairment of glucose metabolism. The potential for less weight loss in patients with a higher FBG should not discourage RYGB, given the significant metabolic improvement after surgery.
    Surgery for Obesity and Related Diseases 01/2013; · 4.12 Impact Factor
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    ABSTRACT: Export Date: 18 October 2014
    01/2013: pages 523-536;
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    ABSTRACT: Diet has a high relevance in health. Hypertension is a major risk factor for cardiovascular diseases and has an important impact on public health, and consequently on countries economy. Scientific research gathered strong evidences about the role of several dietary factors either in etiology or in treatment/prevention of these diseases. Peptides from different food matrices have been studied, and indicated as compounds with particular interest in the context of hypertension. The classical approach involves the identification of peptides with an in vitro ACE inhibitory activity and the assumption that the observed in vivo effects are due to this enzyme blockade. However, in some cases the potency of ACE blockade does not correlate with the antihypertensive activity in vivo. This paper reviews the current literature that identifies mechanisms of action, other than ACE inhibition, that might explain antihypertensive effects of biologically active peptides from different food sources.
    Current pharmaceutical design 06/2012; · 4.41 Impact Factor
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    ABSTRACT: A QuEChERS method has been developed for the determination of 14 organochlorine pesticides in 14 soils from different Portuguese regions with wide range composition. The extracts were analysed by GC-ECD (where GC-ECD is gas chromatography-electron-capture detector) and confirmed by GC-MS/MS (where MS/MS is tandem mass spectrometry). The organic matter content is a key factor in the process efficiency. An optimization was carried out according to soils organic carbon level, divided in two groups: HS (organic carbon >2.3%) and LS (organic carbon <2.3%). The method was validated through linearity, recovery, precision and accuracy studies. The quantification was carried out using a matrix-matched calibration to minimize the existence of the matrix effect. Acceptable recoveries were obtained (70-120%) with a relative standard deviation of ≤16% for the three levels of contamination. The ranges of the limits of detection and of the limits of quantification in soils HS were from 3.42 to 23.77 μg kg(-1) and from 11.41 to 79.23 μg kg(-1), respectively. For LS soils, the limits of detection ranged from 6.11 to 14.78 μg kg(-1) and the limits of quantification from 20.37 to 49.27 μg kg(-1) . In the 14 collected soil samples only one showed a residue of dieldrin (45.36 μg kg(-1) ) above the limit of quantification. This methodology combines the advantages of QuEChERS, GC-ECD detection and GC-MS/MS confirmation producing a very rapid, sensitive and reliable procedure which can be applied in routine analytical laboratories.
    Journal of Separation Science 06/2012; 35(12):1521-30. · 2.59 Impact Factor
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    ABSTRACT: An in vitro digestion/Caco-2 cell culture model was used to assess the stability and bioavailability of phenolic compounds in aqueous extracts of four herbal infusions, traditionally used as functional drinks in Portugal. Alterations in antioxidant power were monitored by ABTS+, whereas the profile of phenolic compounds was ascertained by HPLC-DAD. The bioavailability of rutin – an important flavonoid present in such extracts, and thus a representative of those compounds, was assessed across Caco-2 cells via LC–MS/MS. Our results indicate that several antioxidant compounds are not affected by the (simulated) digestive process, whereas others undergo decreases in their activity throughout said process; a few have their antioxidant capacity hampered under stomach-like conditions. It was also found that rutin can be transported across the Caco-2 cell barrier.
    Food Chemistry. 04/2012; 131(3):761-767.
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    ABSTRACT: Scientific evidence has shown an association between organochlorine compounds (OCC) exposure and human health hazards. Concerning this, OCC detection in human adipose samples has to be considered a public health priority. This study evaluated the efficacy of various solid-phase extraction (SPE) and cleanup methods for OCC determination in human adipose tissue. Octadecylsilyl endcapped (C(18) -E), benzenesulfonic acid modified silica cation exchanger (SA), poly(styrene-divinylbenzene (EN) and EN/RP(18) SPE sorbents were evaluated. The relative sample cleanup provided by these SPE columns was evaluated using gas chromatography with electron capture detection (GC-ECD). The C(18) -E columns with strong homogenization were found to provide the most effective cleanup, removing the greatest amount of interfering substance, and simultaneously ensuring good analyte recoveries higher than 70%. Recoveries > 70% with standard deviations (SD) < 15% were obtained for all compounds under the selected conditions. Method detection limits were in the 0.003-0.009 mg/kg range. The positive samples were confirmed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The highest percentage found of the OCC in real samples corresponded to HCB, o,p'-DDT and methoxychlor, which were detected in 80 and 95% of samples analyzed respectively. Copyright © 2012 John Wiley & Sons, Ltd.
    Biomedical Chromatography 03/2012; 26(12):1494-501. · 1.95 Impact Factor
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    ABSTRACT: The aim of this study was to characterize the intestinal absorption of thiamine, by investigating the hypothesis of an involvement of Organic Cation Transporter (OCT) family members in this process. [(3)H]-T(+) uptake was found to be: 1) time-dependent, 2) Na(+)- and Cl(-)-dependent, 3) pH-dependent, with uptake increasing with a decrease in extracellular pH and decreasing with a decrease in intracellular pH, 4) inhibited by amiloride, 5) inhibited by the thiamine structural analogues oxythiamine and amprolium, 6) inhibited by the unrelated organic cations MPP(+), clonidine, dopamine, serotonin, 7) inhibited by the OCT inhibitors decynium22 and progesterone. Moreover, the dependence of [(3)H]-T(+) uptake on phosphorylation/dephosphorylation mechanisms was also investigated and [(3)H]-T(+) uptake was found to be reduced by PKA activation and protein tyrosine phosphatase and alkaline phosphatase inhibition. In conclusion, our results are compatible with the possibility of thiamine being transported not only by ThTr1 and/or ThTr2, but also by members of the OCT family of transporters (most probably OCT1 and/or OCT3), thus sharing the same transporters with several other organic cations at the small intestinal level.
    European journal of pharmacology 02/2012; 682(1-3):37-42. · 2.59 Impact Factor

Publication Stats

800 Citations
265.34 Total Impact Points

Institutions

  • 2000–2014
    • University of Porto
      • • Faculty of Medicine
      • • Department of Biochemistry
      • • Departamento de Química
      Oporto, Porto, Portugal
  • 2012
    • Polytechnic Institute of Porto
      Oporto, Porto, Portugal
    • REQUIMTE
      Caparica, Setúbal, Portugal