The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury

Neuroinflammation plays an integral role in the progression of neurodegeneration. In this study we investigated the anti-inflammatory effects of different classes of flavonoids (flavanones, flavanols and anthocyanidins) in primary mixed glial cells. We found that the flavanones naringenin and hesperetin and the flavols (+)-catechin and (-)-epicatechin, but not the anthocyanidins cyanidin and pelargonidin, attenuated LPS/IFN-gamma-induced TNF-alpha production in glial cells. Naringenin also inhibited LPS/IFN-gamma-induced iNOS expression and nitric oxide production in glial cells, thus showing the strongest antiinflammatory activity among all flavonoids tested. Moreover, naringenin protected against inflammatory-induced neuronal death in a primary neuronal-glial co-culture system. Naringenin also inhibited LPS/IFN-gamma-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and downstream signal transducer and activator of transcription-1 (STAT-1) in LPS/IFN-gamma stimulated primary mixed glial cells. Taken together, our results suggest that naringenin may produce an anti-inflammatory effect in LPS/IFN-gamma stimulated glial cells that may be due to its interaction with p38 signalling cascades and the STAT-I trascription factor. (C) 2009 Elseiver Inc. All rights reserved.

The differential tissue distribution of the citrus flavanone naringenin following gastric instillation

Citrus flavonoids have been investigated for their biological activity, with both anti-inflammatory and -carcinogenic effects being reported. However, little information is known on the bioavailability of these compounds in vivo. The objectives of this study were to determine the tissue distribution of naringenin after gastric gavage of [H-3]-naringenin to rats. Unlabelled naringenin was also used to quantify the levels of naringenin and its major metabolites in tissues and eliminated in the urine and faeces. Significant radioactivity was detected in the plasma as well as all tissues examined 2 h post-gavage. After 18 h, higher levels of radioactivity were retained in plasma and tissues (55% of the administered radioactivity). Investigation of the nature of metabolites, using unlabelled naringenin, revealed that the glucuronides were the major components in plasma, tissues and urine, in addition to the colonic metabolite 3-(4- hydroxyphenyl) propionic acid, detected in the urine. The aglycone was the form extensively retained in tissues after 18 h post-gavage. Total identified metabolites detected after 18 h in most tissues were only 1-5% of the levels detected after 2 h. However, the brain, lungs and heart retained 27, 20 and 11%, respectively, relative to the total metabolites detected at 2 h. While radioactive detection suggests increased levels of breakdown products of naringenin after 18 h versus 2 h, the products identified using unlabelled naringenin are not consistent with this, suggesting that a predominant proportion of the naringenin breakdown products at 18 h are retained as smaller decomposition molecules which cannot yet be identified.

Comparative analysis by protocol and key of seed storage behaviour of sixty Vietnamese tree species

Seed storage behaviour of 5 1 native and 9 introduced tree species in Vietnam was investigated using a brief protocol developed to aid biodiversity conservation in circumstances where little is known about the seeds. Of the 60 species, 34 appeared to show orthodox (Acacia auriculaeformis, Adenanthera pavonina, Afzelia xylocarpa, Bauhinia purpurea, Callistemon lanceolatus, Cananga odorata, Canarium nigrum, Cassia fistula, Cassia javanica, Cassia splendida, Chukrasia tabularis, Dalbergia bariaensis, Dialium cochinchinensis, Diospyros mollis, Diospyros mun, Dracuntomelon duperreanum, Erythrophleum fordii, Khaya senegalensis, Lagerstroemia speciosa, Leucaena leucocephala, Livistona cochinchinensis, Markhamia stipulata, Melaleuca cajuputi, Millettia ichthyotona, Peltophorum pterocarpum, Peltophorum tonkinensis, Pinus khasya, Pinus massoniana, Pinus merkusii, Pterocarpus macrocarpus, Sindora siamensis, Sophora tonkinense, Sterculia foetida, Swietenia macrophylla), 13 recalcitrant (Avicennia alba, Beilschmiedia roxburghiana, Caryota mitis, Dimocarpus sp., Diospyros malabarica, Dipterocarpus chartaceus, Dypsis pinnatifrons, Hopea odorata, Lithocarpus gigantophylla, Machilus odoratissimus, Melanorrhoea laccifera, Melanorrhea usitata, Syzygium cinereum) and 13 intermediate (Anisoptera cochinchinensis, Aphanamixis polystachya, Averrhoa carambola, Carissa carandas, Chrysopylum cainito, Cinnamomum camphora, Citrofortunella microcarpa, Citrus grandis var. grandis, Elaeis guineensis, Hydnocarpus anthelmintica, Madhuca floribunda, Manilkara achras, Mimusops elengi) seed storage behaviour. A double-criteria key to estimate likely seed storage behaviour showed good agreement with the above: the key can reduce the workload of seed storage behaviour identification considerably.

Modulation of peroxynitrite-induced fibroblast injury by hesperetin: a role for intracellular scavenging and modulation of ERK signalling

Peroxynitrite is thought to contribute to the progression of many diseases including cardiovascular disease, cancer, and neurodegenerative disorders. We report that pre-treatment of fibroblasts with the citrus flavanone, hesperetin, prior to peroxynitrite exposure protects against peroxynitrite-mediated cytotoxicity. This protection was partially mediated by the intracellular scavenging of peroxynitrite by hesperctin as exposure of fibroblasts to peroxynitrite following hesperetin loading led to the formation of two intracellular nitrohesperetin derivatives. In addition, protection appeared to be mediated by hesperetin-induced changes in MAP kinase signalling. Exposure of fibroblasts to hesperetin led to concentration-dependent increases in the phosphorylation of ERK1/2 and was observed to restore peroxynitrite-mediated decreases in ERK1/2 phosphorylation. We propose that the protective potential of hesperetin in fibroblasts may be mediated both by intracellular scavenging of peroxynitrite and by modulation of fibroblast signalling. (c) 2006 Elsevier Inc. All rights reserved.

An investigation and comparison of the bioactivity of selected essential oils on human lice and house dust mites

The insecticidal potency of some essential oils suggests that they may find an application in the control of house dust mites, but current in vitro assays for mites do not appear to give consistent results. A simple, novel, mite chamber assay was therefore developed to carry out testing. Different species of insects are susceptible to different essential oil components, so we compared the relative acaricidal and pediculicidal activity of three essential oils: tea tree, lavender and lemon, because the activity of their constituents on lice ranges from highly active to virtually inactive. The most effective essential oil against both lice and mites was tea tree oil; lavender was the second most effective, and lemon oil the least, although it did show activity against mites, unlike lice. The assay proved simple and effective and gave reproducible results. (c) 2007 Elsevier B.V. All rights reserved.

Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation

Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory, effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300 nM, 15 min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18 h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300 nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Adobe Garamond Premier Pro Greek

In 2003, through a conference presentation in Vancouver and a series of exchanges with Lemon, Leonidas convinced Adobe to substantially extend the coverage of the Greek script in forthcoming Adobe typefaces. The revised brief for Garamond was extended to include, for the first time in a digital typeface, extensive polytonic support, full archaic characters, and small capitals with optional polytonic diacritics; these features should be implemented with respect for the Greek language’s complex rules for case conversion, allowing full dictionary support regardless of the features applied. This project was the first where these issues were addressed, both from a documentation and a development point of view. Leonidas’ responsibilities lay with researching historical and current conventions, developing specifications for the appearance and behaviour of the typefaces, editing glyph outlines, and testing of development versions.

Antioxidant activity of selected phenols and herbs used in diets for medical conditions.

The antioxidant capacity of some herbs used in dietology practice was determined by the DPPH free radical method, which was calibrated with ascorbic acid. Partially hydrophilic phenolic compounds are the most active compounds in plants, and therefore water was used as the extraction agent. Besides antioxidant capacity, the content of total phenolic compounds was also measured and a strong correlation between these two variables was found. The extracts of lemon balm (Melissa officinalis L.), peppermint (Mentha x piperita L.), oregano (Origanum vulgare L.), Greek oregano (Origanum heracleoticum L.), sage (Salvia officinalis L.) and winter savory (Satureja montana L.) showed very significant activity. It was comparable with the activity of green tea in the case of oregano and peppermint. Lower activity was observed in the case of rosemary (Rosmarinus officinalis L.), marjoram (Majorana hortensis), hyssop (Hyssopus officinalis L.), sweet basil (Ocimum basilicum), and lovage (Levisticum officinale Koch.). The inhibitory activity of the herb extracts was monitored also during the autooxidation of lard. Very high antioxidant capacity was observed mainly in sage samples, but also in marjoram and Greek oregano. The extracts of peppermint, oregano, rosemary, winter savory, lemon balm and hyssop showed middle activity comparable to that of alpha-tocopherol. The antioxidant capacity of sweet basil and lovage was insignificant.

The impact of fruit flavonoids on memory and cognition

There is intense interest in the studies related to the potential of phytochemical-rich foods to prevent age-related neurodegeneration and cognitive decline. Recent evidence has indicated that a group of plant-derived compounds known as flavonoids may exert particularly powerful actions on mammalian cognition and may reverse age-related declines in memory and learning. In particular, evidence suggests that foods rich in three specific flavonoid sub-groups, the flavanols, anthocyanins and/or flavanones, possess the greatest potential to act on the cognitive processes. This review will highlight the evidence for the actions of such flavonoids, found most commonly in fruits, such as apples, berries and citrus, on cognitive behaviour and the underlying cellular architecture. Although the precise mechanisms by which these flavonoids act within the brain remain unresolved, the present review focuses on their ability to protect vulnerable neurons and enhance the function of existing neuronal structures, two processes known to be influenced by flavonoids and also known to underpin neuro-cognitive function. Most notably, we discuss their selective interactions with protein kinase and lipid kinase signalling cascades (i.e. phosphoinositide-3 kinase/Akt and mitogen-activated protein kinase pathways), which regulate transcription factors and gene expression involved in both synaptic plasticity and cerebrovascular blood flow. Overall, the review attempts to provide an initial insight into the potential impact of regular flavonoid-rich fruit consumption on normal or abnormal deteriorations in cognitive performance.

Survival of Lactobacillus plantarum in model solutions and fruit juices

The aim of the work was to study the survival of Lactobacillus plantarum NCIMB 8826 in model solutions and develop a mathematical model describing its dependence on pH, citric acid and ascorbic acid. A Central Composite Design (CCD) was developed studying each of the three factors at five levels within the following ranges, i.e., pH (3.0-4.2), citric acid (6-40 g/L), and ascorbic acid (100-1000 mg/L). In total, 17 experimental runs were carried out. The initial cell concentration in the model solutions was approximately 1 × 10(8)CFU/mL; the solutions were stored at 4°C for 6 weeks. Analysis of variance (ANOVA) of the stepwise regression demonstrated that a second order polynomial model fits well the data. The results demonstrated that high pH and citric acid concentration enhanced cell survival; one the other hand, ascorbic acid did not have an effect. Cell survival during storage was also investigated in various types of juices, including orange, grapefruit, blackcurrant, pineapple, pomegranate, cranberry and lemon juice. The model predicted well the cell survival in orange, blackcurrant and pineapple, however it failed to predict cell survival in grapefruit and pomegranate, indicating the influence of additional factors, besides pH and citric acid, on cell survival. Very good cell survival (less than 0.4 log decrease) was observed after 6 weeks of storage in orange, blackcurrant and pineapple juice, all of which had a pH of about 3.8. Cell survival in cranberry and pomegranate decreased very quickly, whereas in the case of lemon juice, the cell concentration decreased approximately 1.1 logs after 6 weeks of storage, albeit the fact that lemon juice had the lowest pH (pH~2.5) among all the juices tested. Taking into account the results from the compositional analysis of the juices and the model, it was deduced that in certain juices, other compounds seemed to protect the cells during storage; these were likely to be proteins and dietary fibre In contrast, in certain juices, such as pomegranate, cell survival was much lower than expected; this could be due to the presence of antimicrobial compounds, such as phenolic compounds.

Continuum sea ice rheology determined from subcontinuum mechanics

[1] A method is presented to calculate the continuum-scale sea ice stress as an imposed, continuum-scale strain-rate is varied. The continuum-scale stress is calculated as the area-average of the stresses within the floes and leads in a region (the continuum element). The continuum-scale stress depends upon: the imposed strain rate; the subcontinuum scale, material rheology of sea ice; the chosen configuration of sea ice floes and leads; and a prescribed rule for determining the motion of the floes in response to the continuum-scale strain-rate. We calculated plastic yield curves and flow rules associated with subcontinuum scale, material sea ice rheologies with elliptic, linear and modified Coulombic elliptic plastic yield curves, and with square, diamond and irregular, convex polygon-shaped floes. For the case of a tiling of square floes, only for particular orientations of the leads have the principal axes of strain rate and calculated continuum-scale sea ice stress aligned, and these have been investigated analytically. The ensemble average of calculated sea ice stress for square floes with uniform orientation with respect to the principal axes of strain rate yielded alignment of average stress and strain-rate principal axes and an isotropic, continuum-scale sea ice rheology. We present a lemon-shaped yield curve with normal flow rule, derived from ensemble averages of sea ice stress, suitable for direct inclusion into the current generation of sea ice models. This continuum-scale sea ice rheology directly relates the size (strength) of the continuum-scale yield curve to the material compressive strength.

An assessment of the prebiotic potential of single and blended substrates in anaerobic in vitro batch culture fermentations using canine faecal samples as inocula

Previously, using an in vitro static batch culture system, it was found that rice bran (RB), inulin, fibersol, mannanoligosaccharides (MOS), larch arabinogalactan and citrus pectin elicited prebiotic effects (in terms of increased numbers of bifidobacteria and lactic acid bacteria) on the faecal microbiota of a dog. The aim of the present study was to confirm the prebiotic potential of each individual substrate using multiple faecal donors, as well as assessing the prebiotic potential of 15 substrate blends made from them. Anaerobic static and stirred, pH-controlled batch culture systems inoculated with faecal samples from healthy dogs were used for this purpose. Fluorescence in situ hybridization (FISH) analysis using seven oligonucleotide probes targeting selected bacterial groups and DAPI (total bacteria) was used to monitor bacterial populations during fermentation runs. High-performance liquid chromatography was used to measure butyrate produced as a result of bacterial fermentation of the substrates. RB and a MOS/RB blend (1:1, w/w) were shown to elicit prebiotic and butyrogenic effects on the canine microbiota in static batch culture fermentations. Further testing of these substrates in stirred, pH-controlled batch culture fermentation systems confirmed the prebiotic and butyrogenic effects of MOS/RB, with no enhancement of Clostridium clusters I and II and Escherichia coli populations.

CASCADE: An Agent Based Framework For Modeling The Dynamics Of Smart Electricity Systems

The Complex Adaptive Systems, Cognitive Agents and Distributed Energy (CASCADE) project is developing a framework based on Agent Based Modelling (ABM). The CASCADE Framework can be used both to gain policy and industry relevant insights into the smart grid concept itself and as a platform to design and test distributed ICT solutions for smart grid based business entities. ABM is used to capture the behaviors of diff erent social, economic and technical actors, which may be defi ned at various levels of abstraction. It is applied to understanding their interactions and can be adapted to include learning processes and emergent patterns. CASCADE models ‘prosumer’ agents (i.e., producers and/or consumers of energy) and ‘aggregator’ agents (e.g., traders of energy in both wholesale and retail markets) at various scales, from large generators and Energy Service Companies down to individual people and devices. The CASCADE Framework is formed of three main subdivisions that link models of electricity supply and demand, the electricity market and power fl ow. It can also model the variability of renewable energy generation caused by the weather, which is an important issue for grid balancing and the profi tability of energy suppliers. The development of CASCADE has already yielded some interesting early fi ndings, demonstrating that it is possible for a mediating agent (aggregator) to achieve stable demandfl attening across groups of domestic households fi tted with smart energy control and communication devices, where direct wholesale price signals had previously been found to produce characteristic complex system instability. In another example, it has demonstrated how large changes in supply mix can be caused even by small changes in demand profi le. Ongoing and planned refi nements to the Framework will support investigation of demand response at various scales, the integration of the power sector with transport and heat sectors, novel technology adoption and diffusion work, evolution of new smart grid business models, and complex power grid engineering and market interactions.

Orange juice–derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease

Background: Epidemiological data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial (RCT) data limit our understanding of mechanisms by which flavanones and their metabolites potentially reduce cardiovascular (CV) risk factors. Objective: We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on CV risk biomarkers in men at moderate CVD risk. Methods: In an acute, randomized, placebo-controlled crossover trial, 16 fasted participants (aged 51-69 y) received orange juice or a hesperidin supplement (both providing 320 mg hesperidin) or control (all matched for sugar and vitamin C content). At baseline and 5 h post-intake, endothelial function (primary outcome), further CV risk biomarkers (i.e. blood pressure, arterial stiffness, cardiac autonomic function, platelet activation and NADPH oxidase gene expression) and plasma flavanone metabolites were assessed. Prior to each intervention, a diet low in flavonoids, nitrate/nitrite, alcohol and caffeine was followed and a standardized low-flavonoid evening meal was consumed. Results: Orange juice intake significantly elevated mean (± SEM) plasma concentrations of 8 flavanone (1.75 ± 0.35 µmol/L, P < 0.0001) and 15 phenolic metabolites (13.27 ± 2.22 µmol/L, P < 0.0001) compared with control at 5 h post-consumption. Despite increased plasma flavanone and phenolic metabolite concentrations, CV risk biomarkers were unaltered. Following hesperidin supplement intake, flavanone metabolites were not different to control, suggesting altered absorption/metabolism compared with the orange juice matrix. Conclusions: Following single-dose flavanone intake within orange juice, we detected circulating flavanone and phenolic metabolites collectively reaching a concentration of 15.20 ± 2.15 µmol/L but observed no effect on CV risk biomarkers. Longer-duration RCTs are required to further examine the previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites.

Exploring smart grid possibilities: a complex systems modelling approach

Smart grid research has tended to be compartmentalised, with notable contributions from economics, electrical engineering and science and technology studies. However, there is an acknowledged and growing need for an integrated systems approach to the evaluation of smart grid initiatives. The capacity to simulate and explore smart grid possibilities on various scales is key to such an integrated approach but existing models – even if multidisciplinary – tend to have a limited focus. This paper describes an innovative and flexible framework that has been developed to facilitate the simulation of various smart grid scenarios and the interconnected social, technical and economic networks from a complex systems perspective. The architecture is described and related to realised examples of its use, both to model the electricity system as it is today and to model futures that have been envisioned in the literature. Potential future applications of the framework are explored, along with its utility as an analytic and decision support tool for smart grid stakeholders.