Prostaglandins, Leukotrienes and Essential Fatty Acids - Articles in Press

Elevated plasma fibrinogen caused by inadequate α-linolenic acid intake can be reduced by replacing fat with canola-type rapeseed oil - Corrected Proof

2010-03-08

Abstract: The effects of canola-type rapeseed oil (RSO) on serum lipids, plasma fibrinogen, lipid oxidation and fatty acids were studied in three groups of subjects, two of which had not been consuming fish in their habitual diets. Forty-two volunteers (35 women, 7 men, 16–62 years) replaced fat with RSO for 6 weeks in a parallel design. The average cholesterol and fibrinogen concentrations were 5.0mmol/l and 2.6g/l, respectively. The intake of α-linolenic acid (α-LLA) was doubled. Efficient competitive inhibition by α-LLA was seen as a decrease in long-chain (LC) n-6 PUFA at 3 weeks. Elevated fibrinogen (2.6–3.9g/l) decreased by 0.95g/l at 6 weeks. Docosahexaenoic acid (22:6n-3) in plasma phospholipids increased at low fibrinogen levels only. The associations and changes in plasma C18 and LC PUFA followed the competitive and metabolic principles of the body, and especially in the case of n-3 PUFA according to the recycling pathway.

Polyunsaturated docosahexaenoic acid suppresses oxidative stress induced endothelial cell calcium influx by altering lipid composition in membrane caveolar rafts - Corrected Proof

Sheng Ye, Li Tan, Jian Ma, Qian Shi, Jieshou Li — 2010-03-08

Abstract: Objective: To determine whether DHA suppresses oxidative stress induced endothelial cell calcium influx by altering lipid composition and TRPC1 distribution in membrane rafts.Methods: Endothelial cells (EC) were pretreated with DHA or stearic acid, then incubated for another 3h with media containing H2O2. Membrane lipid rafts were isolated using the discontinuous sucrose density gradient ultracentrifugation method. Intracellular calcium was detected with laser scanning confocal microscope. TRPC1 protein in membrane fractions was detected by immunoblotting. Membrane fatty acids compositions were analyzed by gas chromatography; raft cholesterol level was assayed by an Amplex Red Cholesterol Assay kit, and DAG concentration was quantified by a DAG kinase assay.Results: DHA significantly reduced oxidative stress induced calcium influx; pretreated with DHA the n-3 PUFAs were significantly increased in raft fractions, as well as saturated myristic acid, palmitic acid content of membrane rafts in EC; while the stearic acid, monounsaturated oleic acid and cis-oleic acid were decreased. Incubation with DHA also significantly reduced the amount of SM and cholesterol levels in the raft. Interestingly, we fractioned plasma membrane subcellular compartments and discovered that certain amounts of TRPC1 existed in detergent-resistant plasma membrane fractions of EC. After DHA treatment, TRPC1 was partly displaced from lipid raft to detergent-soluble membrane fractions.Conclusions: DHA significantly reduces oxidative stress induced endothelial calcium influx, this effect might be associated with, at least in part, altered raft lipid environment, and suppresses TRPC1-mediated calcium signaling pathway by partially displacing TRPC1 from membrane caveolar lipid rafts.

Lipid droplets in inflammation and cancer - Corrected Proof

Patricia T. Bozza, João P.B. J.P.B. Viola — 2010-03-08

Abstract: Accumulation of lipid droplets (also known as lipid bodies or adiposomes) within leukocytes, epithelial cells, hepatocytes and other non-adipocytic cells is a frequently observed phenotype in infectious, neoplastic and other inflammatory conditions. Lipid droplet biogenesis is a regulated cellular process that culminates in the compartmentalization of lipids and of an array of enzymes, protein kinases and other proteins, suggesting that lipid droplets are inducible organelles with roles in cell signaling, regulation of lipid metabolism, membrane trafficking and control of the synthesis and secretion of inflammatory mediators. Enzymes involved in eicosanoid synthesis are localized at lipid droplets and lipid droplets are sites for eicosanoid generation in cells during inflammation and cancer. In this review, we discuss the current evidence related to the biogenesis and function of lipid droplets in cell metabolism and signaling in inflammation and cancer. Moreover, the potential of lipid droplets as markers of disease and targets for novel anti-inflammatory and antineoplastic therapies will be discussed.

Toddler formula supplemented with docosahexaenoic acid (DHA) improves DHA status and respiratory health in a randomized, double-blind, controlled trial of US children less than 3 years of age - Corrected Proof

2010-03-08

Abstract: Studies of docosahexaenoic acid (DHA) intake and status in US toddlers are lacking. One national survey found low DHA intakes. The objectives of this double-blind, randomized study were to (a) determine usual DHA intakes, (b) measure the effect of consuming formulas with DHA on red blood cell (RBC) and plasma DHA and (c) record adverse events in US children between 18 and 36 months of age. Children aged 18–36 months were provided 237-ml formula with 0, 43, or 130mg DHA per day for 60 days. Blood was obtained at 0 and 60 days and 24-hour dietary recalls at 0, 30 and 60 days. Usual median daily DHA intake was 13.3mg. RBC DHA increased in a dose-dependent manner with increasing DHA intake (p<0.05). Toddlers consuming the formula with 130mg DHA per day have fewer adverse events (p=0.007) and a lower incidence of respiratory illness (p=0.024), compared to the formula without DHA. US toddlers have low DHA intake and status. Modest increases in DHA intake in toddlers might improve development, including respiratory health.

Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Québec: Higher fish intake or aging-related change in n-3 fatty acid metabolism? - Corrected Proof

2010-03-08

Abstract: The elderly reportedly have a significantly higher % of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma and red cell lipids. However, these observations are from a few small studies and the health status of the elderly in these studies is for the most part unclear. Since the elderly are susceptible to cardiovascular and neurological illnesses that seem to be related in part to lower intake of n-3 fatty acids it seems paradoxical that their blood levels of EPA and DHA would be higher than in young adults. We report here plasma fatty acid profiles and their response to supplementation with two types of fish oils from several of our recent studies in the moderately healthy elderly. We define the moderately healthy elderly as those who were in good physical condition, had no cognitive decline and, if present, in whom hypothyroidism, hyperlipidemia and/or hypertension were well-controlled. As shown previously, we confirm the higher % EPA and % total n-3 fatty acids (but not DHA) in fasting plasma and extend these findings to include higher plasma concentrations (mg/L) of n-3 fatty acids as well. The EPA-predominant supplement raised DHA only in the young, whereas the DHA-predominant supplement raised EPA more in the young than in the elderly. The moderately healthy elderly clearly have higher plasma n-3 fatty acids but whether this reflects differences in intake versus aging-related changes in n-3 fatty acid metabolism remains to be elucidated.

Fatty acid-derived lipid mediators and blood platelet aggregation - Corrected Proof

M. Lagarde, Chen P., Véricel E., Guichardant M. — 2010-03-08

Abstract: Polyunsaturated fatty acids of nutritional value may affect cell functions after their release from cell lipid storage sites, especially phospholipids, and specific oxygenation by cyclooxygenases, lipoxygenases and cytochrome P450. The end-products, namely prostanoids, leukotrienes, and mono-, di- and tri-hydroxy derivatives exhibit a variety of biological effects, especially on vascular cells, leukocytes and platelets. This paper reviews some results obtained with blood platelets as target cells, showing that various lipoxygenase end-products, mainly mono- and di-hydroxy derivatives, are inhibitors (IC50 in μM range) of arachidonic acid-induced aggregation either at the cycloxygenase or thromboxane receptor site level.

Unsaturated fatty acids as cytoprotective agents in the pancreatic β-cell - Corrected Proof

Noel G. Morgan, Shalinee Dhayal — 2010-03-08

Abstract: It is widely accepted that, in type 2 diabetes, elevated levels of free fatty acids and glucose contribute to a state of glucolipotoxicity in which β-cell function declines and, ultimately, cell viability is compromised. This suggests that β-cells do not readily tolerate chronic elevations in fatty acid levels. In vitro studies suggest, however, that β-cells respond differentially to long chain fatty acids, such that saturated species are lipotoxic whereas long chain mono-unsaturated fatty acids can provide cytoprotection. This difference does not appear to be mediated by a mutual metabolic antagonism between saturated and unsaturated species (although differential alterations in neutral lipid disposition may occur in response to these fatty acids) and the mechanisms remain unclear. This review summaries the current understanding of the actions of mono-unsaturated fatty acids in β-cells and highlights areas of controversy as well as key unresolved issues which require to be addressed.

N-3 vs. saturated fatty acids: Effects on the arterial wall - Corrected Proof

S. Sudheendran, C.C. Chang, R.J. Deckelbaum — 2010-03-08

Abstract: Cardiovascular disease is a leading cause of death worldwide. Atherosclerosis and unstable plaques are underlying causes for cardiovascular diseases. Cardiovascular disease is associated with consumption of diets high in saturated fats. In contrast there is increasing evidence that higher intakes of dietary n-3 fatty acids decrease risk for cardiovascular disease. Recent studies are beginning to clarify how n-3 compared with saturated fatty acids influence cardiovascular disease risk via pathways in the arterial wall. In this paper we will review studies that report on mechanisms whereby dietary fatty acids affect atherosclerosis through modulation of arterial wall lipid deposition, inflammation, cell proliferation, and plaque vulnerability.

Conjugated linoleic acid and inflammatory cell signalling - Corrected Proof

C.M. Reynolds, H.M. Roche — 2010-03-08

Abstract: Conjugated linoleic acids (CLA) are a family of polyunsaturated fatty acids (PUFA), some isomers occurring naturally in beef and dairy products and others being formed as a result of bihydrogenation of vegetable oils to form margarine. Synthetic and natural sources of CLA may have beneficial effects in a range of inflammatory conditions including colitis, atherosclerosis, metabolic syndrome and rheumatoid arthritis. Most of the biological effects have been attributed to the cis9, trans11- (c9, t11-) and the trans10, cis12- (t10, c12-) isomers. Evidence suggests that c9, t11-CLA is responsible for the anti-inflammatory effect attributed to CLA while t10, t12-CLA appears to be responsible for anti-adipogenic effects. This review will focus on the effects of CLA on the inflammatory components associated with insulin resistance, atherosclerosis and Th1 mediated inflammatory disease, at a cellular, systemic and clinical level. Whist CLA may ameliorate certain aspects of the inflammatory response, particularly within cellular and animal models, the relevance of this has yet to be clarified within the context of human health.

Fatty acids and signalling in endothelial cells - Corrected Proof

Robert Ringseis, Klaus Eder — 2010-03-08

Abstract: The endothelium is critical for the maintenance of a proper vessel function. Disturbances of endothelial function, called endothelial dysfunction, have serious implications, and lead to the development of atherosclerosis. It is well established that the risk for atherosclerosis development is influenced by nutritional factors such as the intake of certain fatty acids. Due to the fundamental role of the endothelium for atherosclerosis development, it is, therefore, likely that fatty acids directly influence the function of endothelial cells. The present review aims to explain the divergent effects of different types of fatty acids on cardiovascular disease risk by summarizing in vitro-data on the effects of fatty acids on (1) important signalling pathways involved in the modulation of endothelial cell function, and (2) endothelial cell functional properties, namely vasoactive mediator release and mononuclear cell recruitment, both of which are typically dysregulated during endothelial dysfunction.

Phosphatidylserine-dependent neuroprotective signaling promoted by docosahexaenoic acid - Corrected Proof

Hee-Yong Kim, Mohammed Akbar, Yang-Suk Kim — 2010-03-08

Abstract: Enrichment of polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA, 22:6n−3), in the brain is known to be critical for optimal brain development and function. Mechanisms for DHA’s beneficial effects in the nervous system are not clearly understood at present. DHA is incorporated into the phospholipids in neuronal membranes, which in turn can influence not only the membrane chemical and physical properties but also the cell signaling involved in neuronal survival, proliferation and differentiation. Our studies have indicated that DHA supplementation promotes phosphatidylserine (PS) accumulation and inhibits neuronal cell death under challenged conditions, supporting a notion that DHA is an important neuroprotective agent. This article summarizes our findings on the DHA-mediated membrane-related signaling mechanisms that might explain some of the beneficial effects of DHA, particularly on neuronal survival.

Diet-induced docosahexaenoic acid non-raft domains and lymphocyte function - Corrected Proof

Saame Raza Shaikh — 2010-03-08

Abstract: Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid (PUFA) that generally suppresses the function of T lymphocytes and antigen presenting cells (APCs). An emerging mechanism by which DHA modifies lymphocyte function is through changes in the organization of sphingolipid/cholesterol lipid raft membrane domains. Two contradictory models have been proposed to explain how DHA exerts its effects through changes in raft organization. The biophysical model, developed in model membranes, shows that DHA-containing phospholipids form unique non-raft membrane domains, that are organizationally distinct from lipid rafts, which serve to alter the conformation and/or lateral organization of lymphocyte proteins. In contrast, the cellular model on DHA and rafts shows that DHA suppresses lymphocyte function, in part, by directly incorporating into lipid rafts and altering protein activity. To reconcile opposing biophysical and cellular viewpoints, a major revision to existing models is presented herein. Based largely on quantitative microscopy data, it is proposed that DHA, consumed through the diet, modifies lymphocyte function, in part, through the formation of nanometer scale DHA-rich domains. These nano-scale domains disrupt the optimal raft-dependent clustering of proteins necessary for initial signaling. The data covered in this review highlights the importance of understanding how dietary n-3 PUFAs modify lymphocyte membranes, which is essential toward developing these fatty acids as therapeutic agents for treating inflammatory diseases.

Fatty acid transport across the cell membrane: Regulation by fatty acid transporters - Corrected Proof

2010-03-08

Abstract: Transport of long-chain fatty acids across the cell membrane has long been thought to occur by passive diffusion. However, in recent years there has been a fundamental shift in understanding, and it is now generally recognized that fatty acids cross the cell membrane via a protein-mediated mechanism. Membrane-associated fatty acid-binding proteins (‘fatty acid transporters’) not only facilitate but also regulate cellular fatty acid uptake, for instance through their inducible rapid (and reversible) translocation from intracellular storage pools to the cell membrane. A number of fatty acid transporters have been identified, including CD36, plasma membrane-associated fatty acid-binding protein (FABPpm), and a family of fatty acid transport proteins (FATP1–6). Fatty acid transporters are also implicated in metabolic disease, such as insulin resistance and type-2 diabetes. In this report we briefly review current understanding of the mechanism of transmembrane fatty acid transport, and the function of fatty acid transporters in healthy cardiac and skeletal muscle, and in insulin resistance/type-2 diabetes. Fatty acid transporters hold promise as a future target to rectify lipid fluxes in the body and regain metabolic homeostasis.

Fish consumption, not fatty acid status, is related to quality of life in a healthy population - Corrected Proof

O.J.G. Schiepers, R.H.M. de Groot, J. Jolles, M.P.J. van Boxtel — 2010-03-08

Abstract: Depressive symptoms in the community have a considerable impact on quality of life. Although long-chain polyunsaturated fatty acids (LCPUFA) have frequently been implicated in depressed mood, their relationship with quality of life has scarcely been investigated.This study examined the cross-sectional associations between fish consumption and plasma phospholipid LCPUFA status on the one hand, and quality of life, as measured by the Short Form 36 questionnaire, on the other in a population-based sample. The mental health component of quality of life was not associated with LCPUFA status or fish consumption. Fish consumption showed a positive association with physical well-being, which remained significant after correction for LCPUFA status, suggesting that the relationship between fish consumption and physical well-being is independent of the LCPUFA content of fish. These findings indicate that fish consumption may serve as a proxy for a healthy lifestyle or a favorable nutritional status, which is reflected in better quality of life.

Omega-3 fatty acids in dry eye and corneal nerve regeneration after refractive surgery - Corrected Proof

Jiucheng He, Haydee E.P. Bazan — 2010-03-04

Abstract: Dry eye (DE) is a multifactorial condition that affects the surface of the eye and induces an inflammatory response. Corneal nerves play an important role in the maintenance of a healthy ocular surface. Here we review corneal structure, nerve architecture, DE conditions, and nerve regeneration following corneal surgery and discuss how n-3 fatty acids affect the health of the cornea. Animal studies show that resolvins, compounds derived from eicosapentaenoic acid (EPA), increase tear volume and decrease inflammation induced by DE. After corneal surgery in rabbits, treatment with nerve growth factor (NGF) or pigment epithelial derived factor (PEDF) in conjunction with docosahexaenoic acid (DHA) increase nerve density and corneal epithelial cell proliferation. Increased synthesis of the novel docosanoid, neuroprotectin D1 (NPD1), was found in corneas after the animals were treated with PEDF and DHA. Topical application of these lipids derived from n-3 fatty acids could be useful in treating DE and prevent clinical complications such as cornea erosion and ulcerations.

Fatty acid–genotype interactions and cardiovascular risk - Corrected Proof

Anne M. Minihane — 2010-03-04

Abstract: Cardiovascular disease (CVD) risk and rate of progression is determined by genetic, environmental and behavioural factors. Majority of genotype–diet–CVD phenotype research till date has focussed on the interactive impact of single nucleotide polymorphisms (SNP) and dietary fat composition, on blood lipids levels, with strong evidence of the existence of hypo- and hyper-responders. However, a recognised concern in the field of nutrigenetics is a lack of consistency between findings of different studies. This apparent lack of consistency is likely to be attributable to the impact of factors such as ethnicity and gender on the ‘size’ of nutrigenetic interactions, a clear understanding of which needs to be gained. Although not yet ready for widespread use, in the future a greater use of genetic profiling is likely to enhance current strategies of CVD prediction, and improve the design of more personalised approaches to minimise risk in the individual.

Dietary fatty acids and arthritis - Corrected Proof

S. Hurst, Z. Zainal, B. Caterson, C.E. Hughes, J.L. Harwood — 2010-03-02

Abstract: Musculoskeletal complaints are the second most frequent reason for medical treatments. Within these diseases rheumatoid arthritis (RA) and, especially, osteoarthritis (OA) are common. Although the causes of arthritis are multifactorial and not fully understood, clinical trials have generally shown benefit from dietary n-3 polyunsaturated fatty acids. This has usually been attributed to their anti-inflammatory properties. Recently we have used in vitro model systems to study the molecular mechanism(s) by which n-3 PUFAs may act to alleviate the symptoms of arthritis. These experiments showed that n-3 PUFAs reduce expression of cartilage-degrading proteinases, cyclooxygenase-2 and inflammatory cytokines. Eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) or alpha-linolenic acid. The data provide a scientific rationale for the consumption of n-3 fatty acids as part of a healthy diet and perhaps in treating arthritis.

Fatty liver: Role of inflammation and fatty acid nutrition - Corrected Proof

Christopher D Byrne — 2010-03-02

Abstract: Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver damage, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight in the presence of <10g of daily alcohol consumption. The exact prevalence of NAFLD is uncertain because of the absence of simple noninvasive diagnostic tests to facilitate an estimate of prevalence but in subgroups of people such as those with type 2 diabetes, the prevalence may be as high as 70%. NASH is an important subgroup within the spectrum of NAFLD that progresses over time with worsening fibrosis and cirrhosis, and NASH is associated with increased risk for cardiovascular disease. It is, therefore, important to understand the pathogenesis of NASH specifically, to develop strategies for interventions to treat this condition. The purpose of this review is to discuss the roles of inflammation, fatty acids and fatty acids in nutrition, in the pathogenesis and potential treatment of NAFLD.

n-3 Polyunsaturated fatty acids and autoimmune-mediated glomerulonephritis - Corrected Proof

James J. Pestka — 2010-03-02

Abstract: Consumption of n-3 polyunsaturated fatty acids (PUFAs) found in fish oil suppresses inflammatory processes making these fatty acids attractive candidates for both the prevention and amelioration of several organ-specific and systemic autoimmune diseases. Both pre-clinical and clinical studies have been conducted to determine whether fish oils containing the n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can be used in the prevention and treatment of immunoglobulin A nephropathy (IgAN) and lupus nephritis. In a toxin-induced mouse model that mimics the early stages of IgAN, n-3 PUFA consumption suppresses aberrant interleukin (IL)-6-driven IgA production and mesangial IgA immune complex deposition by impairing phosphorylation of upstream kinases and activation of transcription factors essential for IL-6 gene transcription. n-3 PUFAs can also suppress production of anti-double-stranded DNA IgG antibodies and the resultant development of lupus nephritis in the NZBW F1 mouse and related models. These effects have been linked in part to impaired expression of proinflammatory cytokines and adhesion molecules as well as increases in antioxidant enzymes in kidney and immune organs. Several recent clinical trials have provided compelling evidence that n-3 PUFA supplementation could be useful in treatment of human IgAN and lupus nephritis, although some other studies suggest such supplementation might be without benefit. Future investigations employing genomics/proteomics and novel genetically altered mice should provide further insight into how n-3 PUFAs modulate these diseases as well help to identify clinically relevant biomarkers. The latter could be employed in future well-designed, long-term clinical studies that will resolve current controversies on n-3 PUFA efficacy in autoimmune-mediated glomerulonephritis.

Polyunsaturated fatty acids in the modulation of T-cell signalling - Corrected Proof

Naim Akhtar Khan — 2010-03-02

Abstract: n-3 Polyunsaturated fatty acids (PUFA) have been shown to modulate immune responses. These agents, being considered as adjuvant immunosuppressants, have been used in the treatment of various inflammatory and autoimmune diseases. However, the molecular mechanisms of action of n-3 PUFA-induced immunosuppressive effects are not well-understood. Since exogenous n-3 PUFA, under in vitro and in vivo conditions, are efficiently incorporated into T-cell plasma membranes, a number of recent studies have demonstrated that these agents may modulate T-cell signalling. In this review, the interactions of n-3 PUFA with the second messenger cascade initiated during early and late events of T-cell activation are discussed. We particularly focus on how these fatty acids can modulate the production of diacylglycerol and the activation of protein kinase C, mitogen activated protein kinase, calcium signalling and translocation of transcriptional factors, implicated in the regulation of gene transcription in T-cells.

Cardioprotection by omega-3 fatty acids: Involvement of PKCs? - Corrected Proof

J.-Y. Le Guennec, S. Jude, P. Besson, E. Martel, P. Champeroux — 2010-03-02

Abstract: It has been known since the 1970s that an increased consumption of n-3 long chain polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid has cardioprotective effects. Epidemiological studies have reported that this effect is due to the prevention of the arrhythmias responsible for sudden cardiac death. Mechanistically, different hypotheses have been put forward to give an explanation. Among them, there are a direct effect of the polyunsaturated fatty acids on ion channels and/or a modification of the regulation of ion channels by protein kinase C’s.

Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: A review of human studies - Corrected Proof

2010-02-26

Abstract: Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) are critical for infant and childhood brain development, but levels of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are often low in the Western diet. Increasing evidence from both epidemiological and intervention studies, reviewed here, indicates that DHA supplementation, during pregnancy, lactation, or childhood plays an important role in childhood neurodevelopment. Arachidonic acid (ARA) is also important for infant growth and development. Several studies have demonstrated positive associations between blood DHA levels and improvements on tests of cognitive and visual function in healthy children. Controlled trials also have shown that supplementation with DHA and EPA may help in the management of childhood psychiatric disorders, and improve visual and motor functions in children with phenylketonuria. In all studies, DHA and EPA supplementation is typically well tolerated. Further research is needed to determine optimal doses for efficacy at different developmental ages. The potential long-term benefits of early LCPUFA supplementation also require consideration.

n-3 Polyunsaturated fatty acids—Physiological relevance of dose - Corrected Proof

Wooki Kim, David N. McMurray, Robert S. Chapkin — 2010-02-26

Abstract: n-3 Polyunsaturated fatty acids (PUFA) are widely used for chemotheraphy/chemoprevention of chronic diseases. However, the molecular mechanism(s) by which the bioactive n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) modulate effector pathways are not fully elucidated. Multiple experimental approaches, including use of animal models, cell lines, and human clinical trials, have been utilized to dissect the complex effectors. It is imperative to link these different experimental approaches together in order to interpret outcomes in the context of human physiology and pathophysiology. Unfortunately, the adoption of a broad array of model systems and a wide range of fatty acid exposures (i.e. doses) has made it difficult to interpret biological outcomes. Therefore, in this mini-review we discuss the impact of (a) molecular structure of bioactive fatty acids, (b) dose relevance relative to human consumption, (c) enrichment of fatty acids in sera and tissues following dietary intake, and (d) limitations of cell/tissue culture studies.

The Ninth Fatty Acids and Cell Signalling Meeting (FACS-09) - Corrected Proof

Philip C. Calder — 2010-02-25

The Ninth Fatty Acids and Cell Signalling meeting (FACS-09) was held at Keble College, Oxford from 13th to 16th July 2009. Previous FACS meetings have been held in Paris (1992; organised by E. Nunez), Madison (1994; organised by T. Goodfriend), Maastricht (1996; organised by J. Glatz), Cape Cod (1998; organised by M. Laposata), Gargnano (2001; organised by C. Galli), Bethesda (2003; organised by N. Salem), Paris (2005, organised by M. Lagarde), and Quebec City (2007, organised by S. Cunnane). The aims of FACS-09 were to deliver cutting edge research by internationally renowned academic scientists in an informal atmosphere designed to foster interactions and discussion. The dual themes, “From the membrane to the nucleus” and “From the bench to the bedside”, were designed to foster the bringing together and integration of basic membrane, molecular, and cell biology, studies using animal models, investigations of whole body metabolism and human nutrition, and assessment of therapeutic applications in patients. FACS-09 was attended by 38 speakers, 5 chair persons, 15 sponsor’s representatives, and 6 fatty acid researchers from the Universities of Southampton and Oxford. This issue of PLEFA comprises the proceedings of FACS-09 with contributions from the majority of the speakers. Unfortunately, a small number of speakers were unable to provide papers towards the proceedings. FACS-09 was a tremendous scientific and social success, which was made possible by the generosity of the sponsoring organisations:

Antisecretory, antioxidative and antiapoptotic effects of montelukast on pyloric ligation and water immersion stress induced peptic ulcer in rat - Corrected Proof

Arunachalam Muthuraman, Shailja Sood — 2010-02-15

Abstract: In the present study, we tried to explore the mechanism of montelukast as an antiulcerogenic agent in pyloric ligation (PL) and water immersion stress (WIS) induced peptic ulcer. The ameliorative effects of montelukast (5, 10, and 20mg/kg, p.o.) on gastric volume and total acidity were studied in PL model. We have investigated the alteration in the ulcerative index, thiobarbituric acid reactive substances, reduced glutathione, activity of myeloperoxidase, and total calcium level in both models. Estimation of DNA fragmentation by gel electrophoresis was also performed. Medium and higher doses of montelukast showed significant (p<0.05) ameliorative potential on all the above parameters as compared with omeprazole treated group. DNA fragmentation pattern clearly indicated the antiapoptotic effect of montelukast in preventing mucosal erosion in both models. Hence, the gastroprotective effect of montelukast may be attributed to its antisecretory, antioxidative along with its antiapoptotic effect.