Advances in (poly)phenol research: novel sources, bioavailability, bioaccumulation and bioactivity

In the last decades, increasing scientific evidence has correlated the regular consumption of (poly)phenol-rich foods to a potential reduction of chronic disease incidence and mortality. However, epidemiological evidence on the role of (poly)phenol intake against the risk of some chronic diseases is promising, but not conclusive. In this framework a proper approach to (poly)phenol research is requested, using a step by step strategy. The plant kingdom produces an overwhelming array of structurally diverse secondary metabolites, among which flavonoids and related phenolic and (poly)phenolic compounds constitute one of the most numerous and widely distributed group of natural products. To date, more than 8000 structures have been classified as members of the phytochemical class of (poly)phenol, and among them over 4000 flavonoids have been identified. For this reason, a detailed food (poly)phenolic characterization is essential to identify the compounds that will likely enter the human body upon consumption, to predict the metabolites that will be generated and to unravel the potential effects of phenolic rich food sources on human health. In the first part of this work the attention was focused on the phenolic characterization of fruit and vegetable supplements, considering the increasing attention recently addressed to the so called "nutraceuticals", and on the main coffee industry by-product, namely coffee silverskin. The interest oriented toward (poly)phenols is then extended to their metabolism within the human body, paramount in the framework of their putative health promoting effects. Like all nutrients and non-nutrients, once introduced through the diet, (poly)phenols are subjected to an intense metabolism, able to convert the native compounds into similar conjugated, as well as smaller and deeply modified molecules, which in turn could be further conjugated. Although great strides have been made in the last decades, some steps of the (poly)phenol metabolism remain unclear and are interesting points of research. In the second part of this work the research was focused on a specific bran fraction, namely aleurone, added in feed pellets and in bread to investigate the absorption, metabolism and bioavailability of its phenolic compounds in animal and humans, with a preliminary in vitro step to determine their potential bioaccesibility. This part outlines the best approaches to assess the bioavailability of specific phenolics in several experimental models. The physiological mechanisms explaining the epidemiological and observational data on phenolics and health, are still far from being unraveled or understood in full. Many published results on phenolic actions at cell levels are biased by the fact that aglycones or native compounds have been used, not considering the previously mentioned chemical and biological transformations. In the last part of this thesis work, a new approach in (poly)phenol bioactivity investigation is proposed, consisting of a medium-long term treatment of animals with a (poly)phenol source, in this specific case resveratrol, the detection of its metabolites to determine their possible specific tissue accumulation, and the evaluation of specific parameters and/or mechanism of action at target tissue level. To conclude, this PhD work has contributed to advancing the field, as novel sources of (poly)phenols have been described, the bioavailability of (poly)phenols contained in a novel specific bran fraction used as ingredient has been evaluated in animal and in humans, and, finally, the tissue accumulation of specific (poly)phenol metabolites and the evaluation of specific parameters and/or mechanism of action has been carried out. For these reasons, this PhD work should be considered an example of adequate approach to the investigation of (poly)phenols and of their bioactivity, unavoidable in the process of unequivocally defining their effects on human health.

Topography of visual evoked magnetic responses to pattern shift, pattern onset and flash stimuli

Different visual stimuli may activate separate channels in the visual system and produce magnetic responses from the human bran which originate from distinct regions of the visual cortex. To test this hypothesis, we have investigated the distribution of visual evoked magnetic responses to three distinct visual stimuli over the occipital region of the scalp with a DC-SQUID second-order gradiometer in an ubshielded environment. Patterned stimuli were presented full field and to the right half field, while a flash stimulus was presented full field only, in five normal subjects. Magnetic responses were recorded from 20 to 42 positions over the occipital scalp. Topographic maps were prepared of the major positive component within the first 150ms to the three stimuli, i.e., the P100m (pattern shift), C11m (pattern onset) and P2m (flash). For the pattern shift stimulus the data suggested the source of the P100m was close to the midline with the current directed towards the medial surface. The data for the pattern onset C11m suggested a source at a similar depth but with the current directed away from the midline towards the lateral surface. The flash P2m appeared to originate closer to the surface of the occipital pole than both the patterned stimuli. Hence the pattern shift (which may represent movement), and the pattern onset C11m (representing contrast and contour) appear to originate in similar areas of brain but to represent different asepcts of cortical processing. By contrast, the flash P2m (representing luminance change) appears to originate in a distinct area of visual cortex closer to the occipital pole.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

Background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Uncatalysed and potassium-catalysed pyrolysis of the cell-wall constituents of biomass and their model compounds

Cell-wall components (cellulose, hemicellulose (oat spelt xylan), lignin (Organosolv)), and model compounds (levoglucosan (an intermediate product of cellulose decomposition) and chlorogenic acid (structurally similar to lignin polymer units)) have been investigated to probe in detail the influence of potassium on their pyrolysis behaviours as well as their uncatalysed decomposition reaction. Cellulose and lignin were pretreated to remove salts and metals by hydrochloric acid, and this dematerialized sample was impregnated with 1% of potassium as potassium acetate. Levoglucosan, xylan and chlorogenic acid were mixed with CHCOOK to introduce 1% K. Characterisation was performed using thermogravimetric analysis (TGA) and differential thermal analysis (DTA). In addition to the TGA pyrolysis, pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS) analysis was introduced to examine reaction products. Potassium-catalysed pyrolysis has a huge influence on the char formation stage and increases the char yields considerably (from 7.7% for raw cellulose to 27.7% for potassium impregnated cellulose; from 5.7% for raw levoglucosan to 20.8% for levoglucosan with CHCOOK added). Major changes in the pyrolytic decomposition pathways were observed for cellulose, levoglucosan and chlorogenic acid. The results for cellulose and levoglucosan are consistent with a base catalysed route in the presence of the potassium salt which promotes complete decomposition of glucosidic units by a heterolytic mechanism and favours its direct depolymerization and fragmentation to low molecular weight components (e.g. acetic acid, formic acid, glyoxal, hydroxyacetaldehyde and acetol). Base catalysed polymerization reactions increase the char yield. Potassium-catalysed lignin pyrolysis is very significant: the temperature of maximum conversion in pyrolysis shifts to lower temperature by 70 K and catalysed polymerization reactions increase the char yield from 37% to 51%. A similar trend is observed for the model compound, chlorogenic acid. The addition of potassium does not produce a dramatic change in the tar product distribution, although its addition to chlorogenic acid promoted the generation of cyclohexane and phenol derivatives. Postulated thermal decomposition schemes for chlorogenic acid are presented. © 2008 Elsevier B.V. All rights reserved.

A goal-based modeling approach to develop requirements of an adaptive system with environmental uncertainty

Dynamically adaptive systems (DASs) are intended to monitor the execution environment and then dynamically adapt their behavior in response to changing environmental conditions. The uncertainty of the execution environment is a major motivation for dynamic adaptation; it is impossible to know at development time all of the possible combinations of environmental conditions that will be encountered. To date, the work performed in requirements engineering for a DAS includes requirements monitoring and reasoning about the correctness of adaptations, where the DAS requirements are assumed to exist. This paper introduces a goal-based modeling approach to develop the requirements for a DAS, while explicitly factoring uncertainty into the process and resulting requirements. We introduce a variation of threat modeling to identify sources of uncertainty and demonstrate how the RELAX specification language can be used to specify more flexible requirements within a goal model to handle the uncertainty. © 2009 Springer Berlin Heidelberg.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Avaliação das características de carcaça e perfil dos ácidos graxos em suínos na fase de terminação, alimentados com dietas contendo farelo de bagaço de caju

Provide healthier meat to consumers of pig farmers has required an adjustment of nutrition and feed management. Nutrition is a primary factor in defining the qualitative aspects of pork, because through it we can modify the fatty acid profile. The objective of this study was to analyze the effects of adding bran bagasse cashew (FBC) in diets for finishing pigs, on carcass traits and meat quality. 20 crossbred barrows with an average initial weight of 57.93 ± 3.67 kg / BW were used Diets were formulated based on corn and soybean meal containing vegetable oil, commercial core and different levels of inclusion of the bran bagasse cashew ( 0.0, 7.5 % , 15.0 % , 22.5 % and 30.0 % ) . The experimental design was a randomized block with 5 treatments and 4 replications. Quantitative, qualitative, fatty acid profile of the longissimus muscle and fat area parameters were evaluated. It was observed that with the inclusion of FBC, the parameters of carcass yield, backfat thickness, fat area had a negative linear effect relationship and meat / fat positive effect. Regarding the profile of fatty acids in fat area, the content of linoleic fatty acid level of 30 % of FBC was 18.2 % higher ( P < 0.05 ) at the level of 0.0 % and the arachidonic level of 22.5 % was higher than 33.3 % and 37.5 % at levels of 0.0 % and 15.0 % ( FBC ) respectively. It is concluded that finishing pigs may be food diets containing up to 30 % of FBC, improving the quality of housing for lower fat deposition and modification in the fatty acid profile.

Farelo do bagaço de caju na restrição alimentar qualitativa para suínos em terminação

The objective of this study was to evaluate the effects of the use of cashew bagasse bran (CBB) as food ingredient in qualitative feed restriction programs on the carcass traits, meat quality, organs weight and intestinal morphometry of barrows and gilts. Twenty – four crossbred pigs were used (12 barrows and 12 gilts) with an average initial body weight of 57.93 ± 3.67 kg/LW. The experimental designs was in randomized blocks 3x2 factorial arrangement with three level (0%, 15% e 30% CBB), two genders (barrows and gilts) and four repetition. A total of twenty-four instalments. The treatments were composed of basal diet (BD) formulated with corn, soybean meal and commercial base mix for finishing pigs, being containing different levels of CBB. At the end of the trial period the animals were slaughtered for the evaluation of the meat quality, traits carcass, Absolute Weight (AW) and Relative Weight (RW) of the organs and morphometric study of small intestine fragment. The inclusion of (CBB) in the diets did not affect the traits carcass of gilts, but interfered in the traits carcass of the barrow positively, increasing the yield of meat into cold carcass and reducing the thickness of subcutaneous fat, without affecting the fatty acid profile. However, we observed increased weight of organs and partial volume of absortiva mucosa of gilts. In the comparison between sex was observed a greater liver weight (AW) and (RW), and surface density of absortiva mucosa of barrow. The use of CBB was considered as ingredient to be used in programs of qualitative feed restriction for finishing pigs.

Farelo do bagaço de caju na restrição alimentar qualitativa para suínos em terminação

The objective of this study was to evaluate the effects of the use of cashew bagasse bran (CBB) as food ingredient in qualitative feed restriction programs on the carcass traits, meat quality, organs weight and intestinal morphometry of barrows and gilts. Twenty – four crossbred pigs were used (12 barrows and 12 gilts) with an average initial body weight of 57.93 ± 3.67 kg/LW. The experimental designs was in randomized blocks 3x2 factorial arrangement with three level (0%, 15% e 30% CBB), two genders (barrows and gilts) and four repetition. A total of twenty-four instalments. The treatments were composed of basal diet (BD) formulated with corn, soybean meal and commercial base mix for finishing pigs, being containing different levels of CBB. At the end of the trial period the animals were slaughtered for the evaluation of the meat quality, traits carcass, Absolute Weight (AW) and Relative Weight (RW) of the organs and morphometric study of small intestine fragment. The inclusion of (CBB) in the diets did not affect the traits carcass of gilts, but interfered in the traits carcass of the barrow positively, increasing the yield of meat into cold carcass and reducing the thickness of subcutaneous fat, without affecting the fatty acid profile. However, we observed increased weight of organs and partial volume of absortiva mucosa of gilts. In the comparison between sex was observed a greater liver weight (AW) and (RW), and surface density of absortiva mucosa of barrow. The use of CBB was considered as ingredient to be used in programs of qualitative feed restriction for finishing pigs.

Obtenção e caracterização de um compósito de matriz polimérica com carga de resíduos vegetal proveniente do sabugo de milho

The feasibility of using the corn cob to obtain a polymer matrix composite was studied. To obtain the bran, corncob passed the drying process in a solar dryer, and was subsequently triturated in forage and to obtain the different particle sizes, by sieving. Three different grain sizes were used: fine particles (FP) size between 0,10 and 2mm; sized particles (PM) with sizes between 2,10 and 3,35 mm; large particles (PG) sizes between 3,45 and 4,10 mm. Using 20% of residue relative to the resin, the test samples were constructed for characterization of the composite, taking into account thermal and mechanical parameters. The main advantage of the proposed composite is that it has a low density, below the relative resin, about 1.06 kg / m³ for the PG. The composite showed a mechanical behavior less than of the resin to the grain sizes and for all formulations studied. Showed better results for the bending, reaching 25.3 MPa for the PG. The composite also showed be feasible for thermal applications, with thermal conductivity less than 0.21 W / m, ranking as insulation. In terms of homogeneity of the mixture, the most viable grain size is the PF, which also showed improved aesthetics and better processability. This composite can be used to make structures that do not require significant mechanical strength, such as tables, chairs, planks, and solar and wind prototypes, such as ovens and cookers and turbines blades.

Obtenção e caracterização de um compósito de matriz polimérica com carga de resíduos vegetal proveniente do sabugo de milho

The feasibility of using the corn cob to obtain a polymer matrix composite was studied. To obtain the bran, corncob passed the drying process in a solar dryer, and was subsequently triturated in forage and to obtain the different particle sizes, by sieving. Three different grain sizes were used: fine particles (FP) size between 0,10 and 2mm; sized particles (PM) with sizes between 2,10 and 3,35 mm; large particles (PG) sizes between 3,45 and 4,10 mm. Using 20% of residue relative to the resin, the test samples were constructed for characterization of the composite, taking into account thermal and mechanical parameters. The main advantage of the proposed composite is that it has a low density, below the relative resin, about 1.06 kg / m³ for the PG. The composite showed a mechanical behavior less than of the resin to the grain sizes and for all formulations studied. Showed better results for the bending, reaching 25.3 MPa for the PG. The composite also showed be feasible for thermal applications, with thermal conductivity less than 0.21 W / m, ranking as insulation. In terms of homogeneity of the mixture, the most viable grain size is the PF, which also showed improved aesthetics and better processability. This composite can be used to make structures that do not require significant mechanical strength, such as tables, chairs, planks, and solar and wind prototypes, such as ovens and cookers and turbines blades.

Late Transition Metal-Oxo complexes: Synthesis, and Biorelevant Reactivity

High-valent terminal metal-oxygen adducts are supposed to be potent oxidising intermediates in enzymatic catalyses. In contrast to those from groups 6-8, oxidants that contain late transition metals (Co, Ni, Cu) are poorly understood. Because of their high reactivity, only a few examples of these compounds have been observed. The aim of this project was to investigate the reactivity of high-valent Ni(III) complexes, containing a monodentate oxygen-donor ligands, in hydrogen atom abstraction (HAA) and oxygen atom transfer (OAT) reactions which are typical of biological high-valent metal-oxygen species. Particularly, the Ni(III) complexes were generated in situ, at low temperature, from the oxidation of the Ni(II) species.The nickel complexes studied during this work were supported by tridentate ligands, with a strong σ-donating ability and exceedingly resistant to several common degradation pathways. These complexes vary based on the monodentate group in the fourth coordination position site, which can be neutral or anionic. In particular, we prepared four different Ni(III) complexes [NiIII(pyN2Me2)(OCO2H)] (12), [NiIII(pyN2Me2)(ONO2)] (14), [NiIII(pyN2Me2)(OC(O)CH3)] (18) and [NiIII(pyN2Me2)(OC(O)H)] (25). They feature a bicarbonate (-OCO2H), nitrate (-ONO2), acetate (-OC(O)CH3) and formate (-OC(O)H) group, respectively.HAA and OAT reactions were performed by adding 2,6-di-tert-butylphenol (2,6-DTBP) at -40°C, and triphenylphosphine (PPh3) at -80°C, to the in situ generated Ni(III) complexes, respectively. These reactions were carried out by adding 7 to 500 equivalents of substrate, in order to ensure pseudo-first order conditions. Since, the reactivity of the Ni(III) complex featured by the bicarbonate group has been studied in a previous work, we only investigated that of the species bearing the nitrate, acetate and formate ligand. Finally we compared the value of the reaction rate of all the four species in the HAA and OAT reactions.

Fundamental studies of the application of wheat for malting and brewing

Wheat (Triticum aestivum L.) has a long tradition as a raw material for the production of malt and beer. While breeding and cultivation efforts for barley have been highly successful in creating agronomically and brew- technical optimal specialty cultivars that have become well established as brewing barley varieties, the picture is completely different for brewing wheat. An increasing wheat beer demand results in a rising amount of raw material. Wheat has been - and still is – grown almost exclusively for the baking industry. It is this high demand that defines most of the wheat breeding objectives; and these objectives are generally not favourable in brewing industry. It is of major interest to screen wheat varieties for brewing processability and to give more focus to wheat as a brewing cereal. To obtain fast and reliable predications about the suitability of wheat cultivars a new mathematical method was developed in this work. The method allows a selection based on generally accepted quality characteristics. As selection criteria the parameters raw protein, soluble nitrogen, Kolbach index, extract and viscosity were chosen. During a triannual cultivation series, wheat varieties were evaluated on their suitability for brewing as well as stability to environmental conditions. To gain a fundamental understanding of the complex malting process, microstructural changes were evaluated and visualized by confocal laser scanning and scanning electron microscopy. Furthermore, changes observed in the micrographs were verified and endorsed by metabolic changes using established malt attributes. The degradation and formation of proteins during malting is essential for the final beer quality. To visualise fundamental protein changes taking place during malting, samples of each single process step were analysed and fractioned according their solubility. Protein fractions were analysed using a Lab-on-a-chip technique as well as OFFgel analysis. In general, a different protein distribution of wheat compared to barley or oat could be confirmed. During the malting process a degradation of proteins to small peptides and amino acids could be observed in all four Osborn fractions. Furthermore, in this study a protein profiling was performed to evaluate changes during the mashing process as well as the influence of grist composition. Differences in specific protein peaks and profile were detected for all samples during mashing. This study investigated the suitability of wheat for malting and brewing industry and closed the scientifical gap of amylolytic, cytolytic and proteolytic changes during malting and mashing.

Obtenção de concentrado proteico do farelo de arroz e avaliação das propriedades químicas e funcionais

Esta dissertação é composta por 5 artigos.