Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity

Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-)-epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids.

The influence of dietary fatty acid composition on N-ethyl-Nnitrosourea-induced mammary tumour incidence in the rat and on the composition of inositol- and ethanolamine-phospholipids of normal and tumour mammary tissue

This study has investigated the influence of dietary fatty acid composition on mammary tumour incidence in N-ethyl-N-nitrosourea (ENU)-treated rats and has compared the susceptibility to dietary fatty acid modification of the membrane phospholipids phosphatidyliuositol (PI) and phosphatidylethanolamine (PE) from normal and tumour tissue of rat mammary gland. The incidence of mammary tumours was significantly lower in fish oil- (29%), compared with olive oil- (75%; P < 0.04) but not maize oil- (63%; P < 0.1) fed animals. No differences in PI fatty acid composition were found in normal or tumour tissue between rats fed on maize oil, olive oil or fish oil in diets from weaning. When normal and tumour tissue PI fatty acids were compared, significantly higher amounts of stearic acid (18:O) were found in tumour than normal tissue in rats given olive oil (P < 0.05). A similar trend was found in animals fed on maize oil, although differences between normal and tumour tissue did not reach a level of statistical significance (P < 0.1). In mammary PE, maize oil-fed control animals had significantly higher levels of linoleic acid (18:2n-6) than either olive oil- or fish oil-fed animals (P < 0.05, both cases) and levels of arachidonic acid were also higher in maize oil- compared with fish oil-fed animals (P < 0.05). In tumourbearing animals no differences in PE fatty acid composition were found between the three dietary groups. When normal and tumour tissue PE fatty acids were compared, significantly lower amounts of liuoleic acid (18:2n-6; P < 0.01) and significantly greater amounts of arachidonic acid (20:4n-6; P < 0.05) were found in tumour than normal tissue of rats fed on maize oil. The present study shows that the fatty acid composition of PI from both normal and tumour tissue of the mammary gland is resistant to dietary fatty acid modification. The PE fraction is more susceptible to dietary modification and in this fraction there is evidence of increased conversion of linoleic acid to arachidonic acid in tumour compared with normal tissue. Lower tumour incidence rates in rats given fish oils may in part be due to alteration in prostanoid metabolism secondary to displacement of arachidonic acid by eicosapentaenoic acid, but PE rather than PI would appear to be the most likely locus for diet-induced alteration in prostanoid synthesis in this tissue. Effects of dietary fatty acids other than on the balance of n-6 and n-3 fatty acids, and on prostanoid metabolism, should also be considered. The significance of increased stearic acid content of PI in tumours of olive oil-fed animals and the possible influence of dietary fatty acids on the capacity for stearic acid accumulation requires further study.

Rheology of magmas with bimodal crystal size and shape distributions: insights from analog experiments

Magmas in volcanic conduits commonly contain microlites in association with preexisting phenocrysts, as often indicated by volcanic rock textures. In this study, we present two different experiments that inves- tigate the flow behavior of these bidisperse systems. In the first experiments, rotational rheometric methods are used to determine the rheology of monodisperse and polydisperse suspensions consisting of smaller, prolate particles (microlites) and larger, equant particles (phenocrysts) in a bubble‐free Newtonian liquid (silicate melt). Our data show that increasing the relative proportion of prolate microlites to equant pheno- crysts in a magma at constant total particle content can increase the relative viscosity by up to three orders of magnitude. Consequently, the rheological effect of particles in magmas cannot be modeled by assuming a monodisperse population of particles. We propose a new model that uses interpolated parameters based on the relative proportions of small and large particles and produces a considerably improved fit to the data than earlier models. In a second series of experiments we investigate the textures produced by shearing bimodal suspensions in gradually solidifying epoxy resin in a concentric cylinder setup. The resulting textures show the prolate particles are aligned with the flow lines and spherical particles are found in well‐organized strings, with sphere‐depleted shear bands in high‐shear regions. These observations may explain the measured variation in the shear thinning and yield stress behavior with increasing solid fraction and particle aspect ratio. The implications for magma flow are discussed, and rheological results and tex- tural observations are compared with observations on natural samples.

Simulating the effects of grassland management and grass ensiling on methane emission from lactating cows

A dynamic, mechanistic model of enteric fermentation was used to investigate the effect of type and quality of grass forage, dry matter intake (DMI) and proportion of concentrates in dietary dry matter (DM) on variation in methane (CH(4)) emission from enteric fermentation in dairy cows. The model represents substrate degradation and microbial fermentation processes in rumen and hindgut and, in particular, the effects of type of substrate fermented and of pH oil the production of individual volatile fatty acids and CH, as end-products of fermentation. Effects of type and quality of fresh and ensiled grass were evaluated by distinguishing two N fertilization rates of grassland and two stages of grass maturity. Simulation results indicated a strong impact of the amount and type of grass consumed oil CH(4) emission, with a maximum difference (across all forage types and all levels of DM 1) of 49 and 77% in g CH(4)/kg fat and protein corrected milk (FCM) for diets with a proportion of concentrates in dietary DM of 0.1 and 0.4, respectively (values ranging from 10.2 to 19.5 g CH(4)/kg FCM). The lowest emission was established for early Cut, high fertilized grass silage (GS) and high fertilized grass herbage (GH). The highest emission was found for late cut, low-fertilized GS. The N fertilization rate had the largest impact, followed by stage of grass maturity at harvesting and by the distinction between GH and GS. Emission expressed in g CH(4)/kg FCM declined oil average 14% with an increase of DMI from 14 to 18 kg/day for grass forage diets with a proportion of concentrates of 0.1, and on average 29% with an increase of DMI from 14 to 23 kg/day for diets with a proportion of concentrates of 0.4. Simulation results indicated that a high proportion of concentrates in dietary DM may lead to a further reduction of CH, emission per kg FCM mainly as a result of a higher DM I and milk yield, in comparison to low concentrate diets. Simulation results were evaluated against independent data obtained at three different laboratories in indirect calorimetry trials with COWS consuming GH mainly. The model predicted the average of observed values reasonably, but systematic deviations remained between individual laboratories and root mean squared prediction error was a proportion of 0.12 of the observed mean. Both observed and predicted emission expressed in g CH(4)/kg DM intake decreased upon an increase in dietary N:organic matter (OM) ratio. The model reproduced reasonably well the variation in measured CH, emission in cattle sheds oil Dutch dairy farms and indicated that oil average a fraction of 0.28 of the total emissions must have originated from manure under these circumstances.

In vitro fermentation of linear and alpha-1,2-branched dextrans by the human fecal microbiota

The role of structure and molecular weight in fermentation selectivity in linear α-1,6 dextrans and dextrans with α-1,2 branching was investigated. Fermentation by gut bacteria was determined in anaerobic, pH-controlled fecal batch cultures after 36 h. Inulin (1%, wt/vol), which is a known prebiotic, was used as a control. Samples were obtained at 0, 10, 24, and 36 h of fermentation for bacterial enumeration by fluorescent in situ hybridization and short-chain fatty acid analyses. The gas production of the substrate fermentation was investigated in non-pH-controlled, fecal batch culture tubes after 36 h. Linear and branched 1-kDa dextrans produced significant increases in Bifidobacterium populations. The degree of α-1,2 branching did not influence the Bifidobacterium populations; however, α-1,2 branching increased the dietary fiber content, implying a decrease in digestibility. Other measured bacteria were unaffected by the test substrates except for the Bacteroides-Prevotella group, the growth levels of which were increased on inulin and 6- and 70-kDa dextrans, and the Faecalibacterium prausnitzii group, the growth levels of which were decreased on inulin and 1-kDa dextrans. A considerable increase in short-chain fatty acid concentration was measured following the fermentation of all dextrans and inulin. Gas production rates were similar among all dextrans tested but were significantly slower than that for inulin. The linear 1-kDa dextran produced lower total gas and shorter time to attain maximal gas production compared to those of the 70-kDa dextran (branched) and inulin. These findings indicate that dextrans induce a selective effect on the gut flora, short-chain fatty acids, and gas production depending on their length.

PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.

Sustained polymeric delivery of gene silencing antisense ODNs, siRNA, DNAzymes and ribozymes: in vitro and in vivo studies

Small interfering RNA (siRNA), antisense oligonucleotides (ODNs), ribozymes and DNAzymes have emerged as sequence-specific inhibitors of gene expression that may have therapeutic potential in the treatment of a wide range of diseases. Due to their rapid degradation in vivo, the efficacy of naked gene silencing nucleic acids is relatively short lived. The entrapment of these nucleic acids within biodegradable sustained-release delivery systems may improve their stability and reduce the doses required for efficacy. In this study, we have evaluated the potential in vitro and in vivo use of biodegradable poly (d,l-lactide-co-glycolide) copolymer (PLGA) microspheres as sustained delivery devices for ODNs, ribozyme, siRNA and DNA enzymes. In addition, we investigated the release of ODN conjugates bearing 5′-end lipophilic groups. The in vitro sustained release profiles of microsphere-entrapped nucleic acids were dependent on variables such as the type of nucleic acid used, the nature of the lipophilic group, and whether the nucleic acid used was single or double stranded. For in vivo studies, whole body autoradiography was used to monitor the bio-distribution of either free tritium-labelled ODN or that entrapped within PLGA microspheres following subcutaneous administration in Balb-c mice. The majority of the radioactivity associated with free ODN was eliminated within 24 h whereas polymer-released ODN persisted in organs and at the site of administration even after seven days post-administration. Polymer microsphere released ODN exhibited a similar tissue and cellular tropism to the free ODN. Micro-autoradiography analyses of the liver and kidneys showed similar bio-distribution for polymer-released and free ODNs with the majority of radioactivity being concentrated in the proximal convoluted tubules of the kidney and in the Kupffer cells of the liver. These findings suggest that biodegradable PLGA microspheres offer a method for improving the in vivo sustained delivery of gene silencing nucleic acids, and hence are worthy of further investigation as delivery systems for these macromolecules.

Identification of genetic and phenotypic differences associated with prevalent and non-prevalent Salmonella Enteritidis phage types: analysis of variation in amino acid transport

In this study, differences at the genetic level of 37 Salmonella Enteritidis strains from five phage types (PTs) were compared using comparative genomic hybridization (CGH) to assess differences between PTs. There were approximately 400 genes that differentiated prevalent (4, 6, 8 and 13a) and sporadic (11) PTs, of which 35 were unique to prevalent PTs, including six plasmid-borne genes, pefA, B, C, D, srgC and rck, and four chromosomal genes encoding putative amino acid transporters. Phenotype array studies also demonstrated that strains from prevalent PTs were less susceptible to urea stress and utilized L-histidine, L-glutamine, L-proline, L-aspartic acid, gly-asn and gly-gln more efficiently than PT11 strains. Complementation of a PT11 strain with the transporter genes from PT4 resulted in a significant increase in utilization of the amino acids and reduced susceptibility to urea stress. In epithelial cell association assays, PT11 strains were less invasive than other prevalent PTs. Most strains from prevalent PTs were better biofilm formers at 37 degrees C than at 28 degrees C, whilst the converse was true for PT11 strains. Collectively, the results indicate that genetic and corresponding phenotypic differences exist between strains of the prevalent PTs 4, 6, 8 and 13a and non-prevalent PT11 strains that are likely to provide a selective advantage for strains from the former PTs and could help them to enter the food chain and cause salmonellosis.

Natural food and beverage flavour enhancers

Flavour enhancers are of great importance to the food industry and the consumer, in terms of achieving strong, balanced and preferred product flavour. The understanding and use of flavour enhancers can help to avoid excessive use of individual ingredients such as salt or specific character impact flavours. This chapter first discusses savoury flavour enhancement through the use of ingredients rich in amino acids and 5’nucleotides. It later includes the potential role of peptides and Maillard derived compounds. The role of volatile flavour compounds in the enhancement of salt and sweet taste is also discussed.

Immune factors and fatty acid composition in human milk from river/lake, coastal and inland regions of China

Breast milk fatty acid composition may be affected by maternal diet during gestation and lactation. The influence of dietary and breast milk fatty acids on breast milk immune factors is poorly defined. We determined the fatty acid composition and immune factor concentrations of breast milk from women residing in river & lake, coastal, and inland regions of China, which differ in their consumption of lean fish and oily fish. Breast milk samples were collected on days 3 to 5 (colostrum), 14 and 28 post-partum and analysed for soluble CD14 (sCD14), transforming growth factor (TGF)-β1, TGF-β2, secretory immunoglobulin A (sIgA) and fatty acids. The fatty acid composition of breast milk differed between regions and with time post-partum. The concentrations of all four immune factors in breast milk decreased over time, with sCD14, sIgA and TGF-β1 being highest in colostrum in the river & lake region. Breast milk DHA and arachidonic acid (AA) were positively associated, and γ-linolenic acid and EPA negatively associated, with the concentrations of each of the four immune factors. In conclusion, breast milk fatty acids and immune factors differ between regions in China characterised by different patterns of fish consumption and change during the course of lactation. A higher breast milk DHA and AA concentration is associated with higher concentrations of immune factors in breast milk, suggesting a role for these fatty acids in promoting gastrointestinal and immune maturation of the infant.

The neurochemically diverse intermedius nucleus of the medulla as a source of excitatory and inhibitory synaptic input to the nucleus tractus solitarii

Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes but is poorly investigated. To aid identification of the nucleus, we initially produced three-dimensional reconstructions of the InM in both mouse and rat. Neurochemical analysis including transgenic reporter mice expressing green fluorescent protein in GABA-synthesizing neurons, immunohistochemistry, and in situ hybridization revealed that the InM is neurochemically diverse, containing GABAegric and glutamatergic neurons with some degree of colocalization with parvalbumin, neuronal nitric oxide synthase, and calretinin. Projections from the InM to the nucleus tractus solitarius (NTS) were studied electrophysiologically in rat brainstem slices. Electrical stimulation of the NTS resulted in antidromically activated action potentials within InM neurons. In addition, electrical stimulation of the InM resulted in EPSPs that were mediated by excitatory amino acids and IPSPs mediated solely by GABA(A) receptors or by GABA(A) and glycine receptors. Chemical stimulation of the InM resulted in (1) a depolarization of NTS neurons that were blocked by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonoamide) or kynurenic acid and (2) a hyperpolarization of NTS neurons that were blocked by bicuculline. Thus, the InM contains neurochemically diverse neurons and sends both excitatory and inhibitory projections to the NTS. These data provide a novel pathway that may underlie possible reflex changes in autonomic variables after neck muscle spindle afferent activation.

Gut microbial activity, implications for health and disease: the potential role of metabolite analysis

Microbial metabolism of proteins and amino acids by human gut bacteria generates a variety of compounds including phenol, indole, and sulfur compounds and branched chain fatty acids, many of which have been shown to elicit a toxic effect on the lumen. Bacterial fermentation of amino acids and proteins occurs mainly in the distal colon, a site that is often fraught with symptoms from disorders including ulcerative colitis (UC) and colorectal cancer (CRC). In contrast to carbohydrate metabolism by the gut microbiota, proteolysis is less extensively researched. Many metabolites are low molecular weight, volatile compounds. This review will summarize the use of analytical methods to detect and identify compounds in order to elucidate the relationship between specific dietary proteinaceous substrates, their corresponding metabolites, and implications for gastrointestinal health.

Synthesis, structure and electrochemical properties of some thiosemicarbazone complexes of ruthenium

Reaction of salicylaldehyde thiosemicarbazone (L-1), 2-hydroxyacetophenone thiosemicarbazone (L-2) and 2-hydroxynapthaldehyde thiosemicarbazone (L-3) with [Ru(dmso)(4)Cl-2] affords a family of three dimeric complexes (1), (2) and (3) respectively. Crystal structure of the complex (3) has been determined. In these complexes, each monomeric unit consists of one ruthenium center and two thiosemicarbazone ligands, one of which is coordinated to ruthenium as O,N,S-donor and the other as N,S-donor forming a five-membered chelate ring. Two such monomeric units remain bridged by the sulfur atoms of the O,N,S-coordinated thiosemicarbazones. Due to this sulfur bridging, the two ruthenium centers become so close to each other, that a ruthenium-ruthenium single bond is also formed. All the complexes are diamagnetic in the solid state and in dimethylsulfoxide solution show intense absorptions in the visible and ultraviolet region. Origin of these spectral transitions has been established from DFT calculations. Cyclic voltammetry on the complexes shows two irreversible ligand oxidations on the positive side of SCE and two irreversible ligand reductions on the negative side.

Seasonal variation in the fatty acid composition of milk available at retail in the United Kingdom and implications for dietary intake

Milk and dairy products are major sources of fat in the human diet, but there are few detailed reports on the fatty acid composition of retail milk, trans fatty acids in particular, and how these change throughout the year. Semi-skimmed milk was collected monthly for one year from five supermarkets and analysed for fatty acid composition. Relative to winter, milk sold in the summer contained lower total saturated fatty acid (SFA; 67 vs 72 g/100 g fatty acids) and higher cis-monounsaturated fatty acid (MUFA; 23 vs 21 g/100 g fatty acids) and total trans fatty acid (6.5 vs 4.5 g/100 g fatty acids) concentrations. Concentrations of most trans-18:1 and -18:2 isomers also exhibited seasonal variation. Results were applied to national dietary intakes, and indicated that monthly variation in the fatty acid composition of milk available at retail has limited influence on total dietary fatty acid consumption by UK adults.

Effect of cultivar type and ripening on the polyphenol content of date palm fruit

Date palm (Pheonix dactylifera) fruit contains an array of polyphenols, although how these levels alter with cultivar type and fruit ripening is unclear. Utilizing HPLC and LC-ESI-MS/MS, this study define and quantify an array of hydroxybenzoic acids, hydroxycinnamic acids, and flavonoids in three common cultivars of dates (Ajwa, Barni, and Khalas) at the main ripening stages (kimri, khalal, rutab, and tamr). Polyphenols were at highest concentration at earlier stages of ripening, with concentrations reducing with ripening. The khalal stage of the Ajwa cultivar contained significantly higher (P < 0.001) levels of polyphenols than measured in the Barni and Khalas dates at the same degree of ripening. Furthermore, the Ajwa cultivar was the only one to contain significant quantities of anthocyanidins, in particular at the khalal stage. These data suggest dates are a significant source of polyphenols, especially if the earlier edible ripening stages are consumed or utilized as food ingredients.