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.

Simultaneous chemical reaction and distillation of formaldehyde

The thesis is concerned with the development and testing of a mathematical model of a distillation process in which the components react chemically. The formaldehyde-methanol-water system was selected and only the reversible reactions between formaldehyde and water giving methylene glycol and between formaldehyde and methanol producing hemiformal were assumed to occur under the distillation conditions. Accordingly the system has been treated as a five component system. The vapour-liquid equilibrium calculations were performed by solving iteratively the thermodynamic relationships expressing the phase equilibria with the stoichiometric equations expressing the chemical equilibria. Using optimisation techniques, the Wilson single parameters and Henry's constants were calculated for binary systems containing formaldehyde which was assumed to be a supercritical component whilst Wilson binary parameters were calculated for the remaining binary systems. Thus the phase equilibria for the formaldehyde system could be calculated using these parameters and good accuracy was obtained when calculated values were compared with experimental values. The distillation process was modelled using the mass and energy balance equations together with the phase equilibria calculations. The plate efficiencies were obtained from a modified A.I.Ch.E. Bubble Tray method. The resulting equations were solved by an iterative plate to plate calculation based on the Newton Raphson method. Experiments were carried out in a 76mm I.D., eight sieve plate distillation column and the results were compared with the mathematical model calculations. Overall, good agreement was obtained but some discrepancies were observed in the concentration profiles and these may have been caused by the effect of limited physical property data and a limited understanding of the reactions mechanism. The model equations were solved in the form of modular computer programs. Although they were written to describe the steady state distillation with simultaneous chemical reaction of the formaldehyde system, the approach used may be of wider application.

Enterotoxigenic Escherichia coli infection of pigs: expression, extraction, purification and the adhesive properties of the K88 fimbrial adhesin

The ability of Escherichia coli to express the K88 fimbrial adhesin was satisfactorily indicated by the combined techniques of ELISA, haemagglutination and latex agglutination. Detection of expression by electron microscopy and the ability to metabolize raffinose were unsuitable. Quantitative expression of the K88 adhesin was determined by ELISA. Expression was found to vary according to the E.coli strain examined, media type and form. In general it was found that the total amount was greater, while the amount/cfu was less on agar than in broth cultures. Expression of the K88 adhesin during unshaken batch culture was related to the growth rate and was maximal during late logarithmic to early stationary phase. A combination of heat extraction, ammonium sulphate and isoelectric precipitation was found suitable for both large and small scale preparation of purified K88ab adhesin. Extraction of the K88 adhesin was sensitive to pH and it was postulated that this may affect the site of colonisation of by ETEC in vivo. Results of haemagglutination experiments were consistent with the hypothesis that the K88 receptor present on erythrocytes is composed of two elements, one responsible for the binding of K88ab and K88ac and a second responsible for the binding of the K88ad adhesin. Comparison of the haemagglutinating properties of cell-free and cell-bound K88 adhesin revealed some differences probably indicating a minor conformational change in the K88 adhesin on its isolation. The K88ab adhesin was found to bind to erythrocytes over a wide pH range (PH 4-9) and was inhibited by αK88ab and αK88b antisera. Inhibition of haemagglutination was noted with crude heparin, mannan and porcine gastric mucin, chondrosine and several hexosamines, glucosamine in particular. The most potent inhibitor of haemagglutination was n-dodecyl-β-D-glucopyranoside, one of a series of glucosides found to have inhibitory properties. Correlation between hydrophobicity of glucosides tested and degree of inhibition observed suggested hydrophobic forces were important in the interaction of the K88 adhesin with its receptor. The results of Scatchard and Hill plots indicated that binding of the K88ab adhesin to porcine enterocytes in the majority of cases is a two-step, three component system. The first K88 receptor (or site) had a K2. of 1.59x1014M-1 and a minimum of 4.3x104 sites/enterocyte. The second receptor (or site) had a K2 of 4.2x1012M-1 with a calculated 1.75x105 sites/enterocyte. Attempts to inhibit binding of cell-free K88 adhesin to porcine enterocytes by lectins were unsuccessful. However, several carbohydrates including trehalose, lactulose, galactose 1→4 mannopyranoside, chondrosine, galactosamine, stachyose and mannan were inhibitory. The most potent inhibitor was found to be porcine gastric mucin. Inhibition observed with n-octyl-α-D-glucopyranose was difficult to interpret in isolation because of interference with the assay, however, it agreed with the results of haemagglutination inhibition experiments.

Adhesive bonding of aluminium

Adhesive bonding of aluminium is widely used in the aerospace industry. High initial bood strengths can be obtained, but bond failure occurs atter prolonged exposure to humid enviroments. The thesis contains details ot a test procedure which has been designed and developed for the assessment of different alloys, pretreatments, and adhesives, which will give adhesively bonded aluminium joints of high strength coupled with long term durability. The test involves assembly of lap shear specimens in a precision jig using 250 ballotini spacers in the adhesive to control the bond line thickness. The test is modified by drilling three accurately located holes through the bonded area after assembly of the joint and curing of the adhesive. Further important features at the test, such as fillet control, are detailed. The test was assessed, modified and developed to give a reliable and reproducible method which would discriminate amongst different bonding systems after exposure to humid test environments. This is the first test to have achieved the discrimination necessary for short term assessment of bond systems where long term durability is required. Even better discrimination has been obtained by applying stress in a stress humidity test. Having established accurate, reliable and discriminating test methods they were used to study the durability of structural epoxy adhesive bonds to aluminium as a function of alloy, pretreatment, adhesive and environment. It was established that the long term durability or adhesively bonded aluminium was directly related to the infulence of water migrating within the adhesive. Pretreatments differed in their ability to prevent hydration of the aluminium oxide by the water absorbed within the adhesive.

Skin adhesive hydrogels for the topical delivery of active agents

This thesis illustrates the development of tailor-made, partially hydrated skin adhesive hydrogels as a vehicle for the topical delivery of moisturising agents. Maintaining an optimum hydration level of the stratum corneum ensures that the barrier properties of the skin are preserved. An unsaturated ionic monomer 2-acrylamido-2-methylpropanesulfonic acid sodium salt, glycerol, water, a photoinitiator Irgacure 184 and crosslinker Ebacryl II facilitated the production of monophasic sheet skin adhesives using photopolymerisation. The exploration and modification of the hydrogel components coupled with their influence on the adhesive and dynamic mechanical behaviour led to the development of novel monophasic and biphasic hydrogels. Biphasic pregels comprising of a hydrophobic monomer (epoxidised soybean oil acrylate, lauryl acrylate or stearyl acrylate) micellised with a non ionic surfactant Tween 60 allowed a homogeneous distribution throughout a predominantly hydrophilic phase (2-acrylamido-2-methylpropanesulfonic acid sodium salt, 4-acryloylmorpholine, glycerol and water). Further development of biphasic hydrogel technology led to the incorporation of preformed commercial O/W emulsions (Acronal, Flexbond 150, DM137 or Texicryl 13056WB) allowing the hydrophobic component to be added without prior stabilisation. The topical release of moisturising agents 2-pyrrolidone-5-carboxylic acid, lactobionic acid and d-calcium pantothenate results in the deposition onto the skin by an initial burst mechanism. The hydration level of the stratum corneum was measured using a Comeometer CM 825, Skin Reader MY810 or FT-ATR. The use of hydrophilic actives in conjunction with lipophilic agents for example Vitamin E or Jojoba oil provided an occlusive barrier, which reduced the rate of transepidermal water loss. The partition coefficients of the release agents provided invaluable information which enabled the appropriate gel technology to be selected. In summary the synthetic studies led to the understanding and generation of transferable technology. This enabled the synthesis of novel vehicles allowing an array of actives with a range of solubilities to be incorporated.

Adhesive wear of modern and traditional engineering coatings

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A bio-adhesive formulation for the delivery of anti-fungal agents to the oesophagus

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Phenol methylation over nanoparticulate Co2FeO4 inverse spinel catalysts:the effect of morphology on catalytic performance

A series of CoFe2O4 nanoparticles have been prepared via co-precipitation and controlled thermal sintering, with tunable diameters spanning 7–50 nm. XRD confirms that the inverse spinel structure is adopted by all samples, while XPS shows their surface compositions depend on calcination temperature and associated particle size. Small (<20 nm) particles expose Fe3+ enriched surfaces, whereas larger (∼50 nm) particles formed at higher temperatures possess Co:Fe surface compositions close to the expected 1:2 bulk ratio. A model is proposed in which smaller crystallites expose predominately (1 1 1) facets, preferentially terminated in tetrahedral Fe3+ surface sites, while sintering favours (1 1 0) and (1 0 0) facets and Co:Fe surface compositions closer to the bulk inverse spinel phase. All materials were active towards the gas-phase methylation of phenol to o-cresol at temperatures as low as 300 °C. Under these conditions, materials calcined at 450 and 750 °C exhibit o-cresol selectivities of ∼90% and 80%, respectively. Increasing either particle size or reaction temperature promotes methanol decomposition and the evolution of gaseous reductants (principally CO and H2), which may play a role in CoFe2O4 reduction and the concomitant respective dehydroxylation of phenol to benzene. The degree of methanol decomposition, and consequent H2 or CO evolution, appears to correlate with surface Co2+ content: larger CoFe2O4 nanoparticles have more Co rich surfaces and are more active towards methanol decomposition than their smaller counterparts. Reduction of the inverse spinel surface thus switches catalysis from the regio- and chemo-selective methylation of phenol to o-cresol, towards methanol decomposition and phenol dehydroxylation to benzene. At 300 °C sub-20 nm CoFe2O4 nanoparticles are less active for methanol decomposition and become less susceptible to reduction than their 50 nm counterparts, favouring a high selectivity towards methylation.

Probing the Role of Thermally Reduced Graphene Oxide in Enhancing Performance of TiO2 in Photocatalytic Phenol Removal from Aqueous Environments

We thank the INSA-RSE bilateral exchange programme for financial assistance (PD) and the Petroleum Technology Development Fund (PTDF, Nigeria) for the award of PhD scholarship, as well as Abubakar Tafawa Balewa University, Bauchi-Nigeria for the granted fellowship (H.A).

Probing the Role of Thermally Reduced Graphene Oxide in Enhancing Performance of TiO2 in Photocatalytic Phenol Removal from Aqueous Environments

We thank the INSA-RSE bilateral exchange programme for financial assistance (PD) and the Petroleum Technology Development Fund (PTDF, Nigeria) for the award of PhD scholarship, as well as Abubakar Tafawa Balewa University, Bauchi-Nigeria for the granted fellowship (H.A).

Gas-solid coexistence of adhesive spheres

In this note, the authors investigate whether the gas-liquid critical point can remain stable with respect to solidification for narrow attractive interactions down to the Baxter limit. Using a crude cell theory, the authors estimate the necessary conditions for this to be true. Possible realizations are briefly discussed.

Development and reliability of a direct access sensor using flip chip on flex technology with anisotropic conductive adhesive

Technological developments in biomedical microsystems are opening up new opportunities to improve healthcare procedures. Swallowable diagnostic sensing capsules are an example of these. In none of the diagnostic sensing capsules, is the sensor’s first level packaging achieved via Flip Chip Over Hole (FCOH) method using Anisotropic Conductive Adhesive (ACA). In a capsule application with direct access sensor (DAS), ACA not only provides the electrical interconnection but simultaneously seals the interconnect area and the underlying electronics. The development showed that the ACA FCOH was a viable option for the DAS interconnection. Adequate adhesive formed a strong joint that withstood a shear stress of 120N/mm2 and a compressive stress of 6N required to secure the final sensor assembly in place before encapsulation. Electrical characterization of the ACA joint in a fluid environment showed that the ACA was saturated with moisture and that the ions in the solution actively contributed to the leakage current, characterized by the varying rate of change of conductance. Long term hygrothermal aging of the ACA joint showed that a thermal strain of 0.004 and a hygroscopic strain of 0.0052 were present and resulted in a fatigue like process. In-vitro tests showed that high temperature and acidity had a deleterious effect of the ACA and its joint. It also showed that the ACA contact joints positioned at around or over 1mm would survive the gastrointestinal (GI) fluids and would be able to provide a reliable contact during the entire 72hr of the GI transit time. A final capsule demonstrator was achieved by successfully integrating the DAS, the battery and the final foldable circuitry into a glycerine capsule. Final capsule soak tests suggested that the silicone encapsulated system could survive the 72hr gut transition.