Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans

Dietary alpha-linolenic acid (ALA) can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on risk factors for coronary heart disease (CHID). This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects. A placebo-controlled, parallel study was conducted in 150 moderately hyperlipidemic subjects, age 25-72 y. Subjects were randomly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA, 4.5 or 9.5g/d ALA or control (linoleic acid; LA) for 6 mo. Fatty acids were incorporated into 25 g of fat spread, which replaced the subject's normal spread and three capsules. Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa, VIIc, VIIag, XIIa, XIIag, fibrinogen concentrations, plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control. (n-3) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors.

Distribution of [H-3]trans-resveratrol in rat tissues following oral administration

Resveratrol has been widely investigated for its potential health properties, although little is known about its metabolism in vivo. Here we investigated the distribution of metabolic products of [H-3]trans-resveratrol, following gastric administration. At 2 h, plasma concentrations reached 1 center dot 7 % of the administered dose, whilst liver and kidney concentrations achieved 1 center dot 0 and 0 center dot 6 %, respectively. Concentrations detected at 18 h were lower, being only 0 center dot 5 % in plasma and a total of 0 center dot 35 % in tissues. Furthermore, whilst kidney and liver concentrations fell to 10 and 25 %, respectively, of concentrations at 2 h, the brain retained 43 % of that measured at 2 h. Resveratrol-glucuronide was identified as the major metabolite, reaching 7 mu m in plasma at 2 h. However, at 18 h the main form identified in liver, heart, lung and brain was native resveratrol aglycone, indicating that it is the main form retained in the tissues. No phenolic degradation products were detected in urine or tissues, indicating that, unlike flavonoids, resveratrol does not appear to serve as a substrate for colonic microflora. The present study provides additional information about the nature of resveratrol metabolites and which forms might be responsible for its in vivo biological effects.

Understanding omega-3 polyunsaturated fatty acids

Current intakes of very long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids also. Very long-chain omega-3 fatty acids are readily incorporated from capsules into transport (blood lipids), functional (cell and tissue), and storage (adipose) pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, lipid-mediator generation, cell signaling, and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology and the way cells and tissues respond to external signals. In most cases the effects seen are compatible with improvements in disease biomarker profiles or health-related outcomes. As a result, very long-chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long-chain omega-3 fatty acids not only protect against cardiovascular morbidity but also against mortality. In some conditions, for example rheumatoid arthritis, they may be beneficial as therapeutic agents. On the basis of the recognized health improvements brought about by long-chain omega-3 fatty acids, recommendations have been made to increase their intake. The plant omega-3 fatty acid, alpha-linolenic acid (ALA), can be converted to EPA, but conversion to DHA appears to be poor in humans. Effects of ALA on human health-related outcomes appear to be due to conversion to EPA, and since this is limited, moderately increased consumption of ALA may be of little benefit in improving health outcomes compared with increased intake of preformed EPA + DHA.

Omega-3 polyunsaturated fatty acids and human health outcomes

Current intakes of very long chain omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DNA) are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids too. Very long chain w-3 fatty acids are readily incorporated from capsules into transport, functional, and storage pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, eicosanoid generation, cell signaling and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology, and the way cells and tissues respond to external signals. In most cases, the effects seen are compatible with improvements in disease biomarker profiles or in health-related outcomes. As a result, very long chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long chain omega-3 fatty acids protect against cardiovascular morbidity and mortality, and might be beneficial in rheumatoid arthritis, inflammatory bowel diseases, childhood learning, and behavior, and adult psychiatric and neurodegenerative illnesses. DHA has an important structural role in the eye and brain, and its supply early in life is known to be of vital importance. On the basis of the recognized health improvements brought about by long chain omega-3 fatty acids, recommendations have been made to increase their intake. (C) 2009 International Union of Biochemistry and Molecular Biology, Inc. Volume 35, Number 3, May/June 2009, Pages 266-272. E-mail: pcc@soton.ac.uk

Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [C-13]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men

The effect of increased dietary intakes of alpha-linolenic acid (ALNA) or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 2 months upon plasma lipid composition and capacity for conversion of ALNA to longer-chain metabolites was investigated in healthy men (52 (SD 12) years). After a 4-week baseline period when the subjects substituted a control spread, a test meal containing [U-C-13]ALNA (700 mg) was consumed to measure conversion to EPA, docosapentaenoic acid (DPA) and DHA over 48 h. Subjects were then randomised to one of three groups for 8 weeks before repeating the tracer study: (1) continued on same intake (control, n 5); (2) increased ALNA intake (10 g/d, n 4); (3) increased EPA+DHA intake (1.5 g/d, n 5). At baseline, apparent fractional conversion of labelled ALNA was: EPA 2.80, DPA 1.20 and DRA 0.04%. After 8 weeks on the control diet, plasma lipid composition and [C-13]ALNA conversion remained unchanged compared with baseline. The high-ALNA diet resulted in raised plasma triacylglycerol-EPA and -DPA concentrations and phosphatidylcholine-EPA concentration, whilst [C-13]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [C-13]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [C-13]ALNA conversion to DHA was unchanged. The dietary interventions did not alter partitioning of ALNA towards beta-oxidation. The present results indicate ALNA conversion was down-regulated by increased product (EPA+DHA) availability, but was not up-regulated by increased substrate (ALNA) consumption. This suggests regulation of ALNA conversion may limit the influence of variations in dietary n-3 fatty acid intake on plasma lipid compositions.

Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians

Background: Indian Asians in Western countries have a higher rate of coronary artery disease than do the indigenous white populations, and this higher rate may be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Objective: The objective of the study was to test the hypothesis that a high background dietary intake of n-6 PUFA attenuates the effects of fish-oil supplementation on insulin sensitivity and associated blood lipids of the metabolic syndrome. Design: Twenty-nine Indian Asian men were recruited to participate in a 12-wk dietary intervention trial. Volunteers were randomly assigned to receive either a moderate or a high n-6 PUFA diet featuring modified oils and spreads over a 6-wk period. After this 6-wk period, both groups were supplemented with 4.0 g fish oil/d (2.5 g eicosapentaenoic acid + docosahexaenoic acid) for an additional 6 wk in combination with the dietary treatment. Volunteers participated in a postprandial study and an insulin sensitivity test after the 6-wk dietary intervention and again after the fish-oil supplementation period. Results: There was no significant time X treatment interaction for blood lipids or insulin action after dietary intervention with the moderate or high n-6 PUFA diets in combination with fish oil. After the 6-wk period of fish oil supplementation, fasting and postprandial plasma triacylglycerol concentrations decreased significantly. Conclusion: The background dietary n-6 PUFA concentration did not modulate the effect of fish-oil supplementation on blood lipids or measures of insulin sensitivity in this ethnic group.

Kinetic modeling of the generation of 2-and 3-methylbutanal in a heated extract of beef liver

Quantitative control of aroma generation during the Maillard reaction presents great scientific and industrial interest. Although there have been many studies conducted in simplified model systems, the results are difficult to apply to complex food systems, where the presence of other components can have a significant impact. In this work, an aqueous extract of defatted beef liver was chosen as a simplified food matrix for studying the kinetics of the Mallard reaction. Aliquots of the extract were heated under different time and temperature conditions and analyzed for sugars, amino acids, and methylbutanals, which are important Maillard-derived aroma compounds formed in cooked meat. Multiresponse kinetic modeling, based on a simplified mechanistic pathway, gave a good fit with the experimental data, but only when additional steps were introduced to take into account the interactions of glucose and glucose-derived intermediates with protein and other amino compounds. This emphasizes the significant role of the food matrix in controlling the Maillard reaction.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Preparation of enantiopure long chain threo-2-amino-3-hydroxyesters via chiral morpholinone-derived azomethine ylids

The synthetic approach to threo-2-amino-3-hydroxyesters possessing long alkyl chains outlined herein centres on the generation of chiral azomethine ylids by reaction of (5R)-5-phenyl-morpholin-2-one, (R)-(1), with long chain aldehydes. In the presence of a second equivalent of aldehyde, the azomethine ylid can be trapped to afford a cycloadduct with three new stereodefined centres. Degradation of the cycloadduct allows entry to beta-substituted-alpha-amino acid derivatives, which have potential as building blocks for sphingosine synthesis.

Dietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase-dependent anti-oxidant response element activity and up-regulates glutathione in cortical astrocytes

Flavonoids are plant-derived polyphenolic compounds with neuroprotective properties. Recent work suggests that, in addition to acting as hydrogen donors, they activate protective signalling pathways. The anti-oxidant response element (ARE) promotes the expression of protective proteins including those required for glutathione synthesis (xCT cystine antiporter, gamma-glutamylcysteine synthetase and glutathione synthase). The use of a luciferase reporter (ARE-luc) assay showed that the dietary flavan-3-ol (-)epicatechin activates this pathway in primary cortical astrocytes but not neurones. We also examined the distribution of NF-E2-related factor-2 (Nrf2), a key transcription factor in ARE-mediated gene expression. We found, using immunocytochemistry, that Nrf2 accumulated in the nuclei of astrocytes following exposure to tert-butylhydroquinone (100 mu M) and (-)epicatechin (100 nM). (-)Epicatechin signalling via Nrf2 was inhibited by wortmannin implicating a phosphatidylinositol 3-kinase-dependent pathway. Finally, (-)epicatechin increased glutathione levels in astrocytes consistent with an up-regulation of ARE-mediated gene expression. Together, this suggests that flavonoids may be cytoprotective by increasing anti-oxidant gene expression.

Integrating Hamiltonian systems defined on the Lie groups SO(4) and SO(1,3)

This paper examines optimal solutions of control systems with drift defined on the orthonormal frame bundle of particular Riemannian manifolds of constant curvature. The manifolds considered here are the space forms Euclidean space E³, the spheres S³ and the hyperboloids H³ with the corresponding frame bundles equal to the Euclidean group of motions SE(3), the rotation group SO(4) and the Lorentz group SO(1,3). The optimal controls of these systems are solved explicitly in terms of elliptic functions. In this paper, a geometric interpretation of the extremal solutions is given with particular emphasis to a singularity in the explicit solutions. Using a reduced form of the Casimir functions the geometry of these solutions is illustrated.

Integrable Hamiltonian systems defined on the Lie groups SO(3) and SU(2): an application to the attitude control of a spacecraft

This paper considers left-invariant control systems defined on the Lie groups SU(2) and SO(3). Such systems have a number of applications in both classical and quantum control problems. The purpose of this paper is two-fold. Firstly, the optimal control problem for a system varying on these Lie Groups, with cost that is quadratic in control is lifted to their Hamiltonian vector fields through the Maximum principle of optimal control and explicitly solved. Secondly, the control systems are integrated down to the level of the group to give the solutions for the optimal paths corresponding to the optimal controls. In addition it is shown here that integrating these equations on the Lie algebra su(2) gives simpler solutions than when these are integrated on the Lie algebra so(3).

Distributed space-time block coding for 3 and 4 relay nodes: Imperfect synchronisation and a solution

Most research on distributed space time block coding (STBC) has so far focused on the case of 2 relay nodes and assumed that the relay nodes are perfectly synchronised at the symbol level. By applying STBC to 3-or 4-relay node systems, this paper shows that imperfect synchronisation causes significant performance degradation to the conventional detector. To this end, we propose a new STBC detection solution based on the principle of parallel interference cancellation (PIC). The PIC detector is moderate in computational complexity but is very effective in suppressing the impact of imperfect synchronisation.