54 articles - 08.09.10
1: J Thorac Cardiovasc Surg. 2010 Aug 12; [Epub ahead of print]
Byrne J, McGuinness J, Chen G, Hill AD, Redmond MJ.
Department of Surgical Research, the Royal College of Surgeons in Ireland, Dublin, Ireland.
OBJECTIVES: Neutrophil infiltration of tissues as part of the inflammatory response to cardiac surgery is one of the major mediators of postoperative multiple-organ dysfunction. Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesion molecules. The efficacy of a clinically safe form of omega-3 to produce this effect in vivo was examined. METHODS: Rat gut intravital microscopic analysis was used to visualize neutrophil transmigration from the microcirculation into the tissues of the gut. Inflammatory activation was in the form of 30 minutes of ischemia and 90 minutes of reperfusion. Sham, control (0.9% saline infusion over 4 hours), and omega-3 (Omegaven [Fresenius Kabi, Bad Homburg, Germany] infusion over 4 hours) pretreatments were compared. RESULTS: Ischemia-reperfusion resulted in a 4-fold increase in neutrophil adherence to the endothelium (baseline: 4.3 +/- 0.2 vs control group: 19.2 +/- 3.5 adherent neutrophils per 100 mum, P < .01), which intravenous omega-3 suppressed (7.8 +/- 1.7 adherent neutrophils per 100 mum, P < .01). Omega-3 pretreatment also reduced neutrophil transmigration into the tissues after reperfusion (sham group: 6.3 +/- 0.8 vs control group: 13.2 +/- 1.4 vs omega-3 group: 9.4 +/- 0.9 neutrophils per field, P = .037). Gut tissue levels of the neutrophil-released enzyme myeloperoxidase were similarly markedly reduced with omega-3 pretreatment (sham group: 10.5 +/- 1.6 vs control group: 19.0 +/- 3.3 vs omega-3 group: 10.1 +/- 1.2 U/g, P = .03). CONCLUSIONS: Four hours' pretreatment with a relatively safe form of intravenous omega-3 suppressed neutrophil adherence and tissue infiltration, resulting in lower levels of the tissue-damaging enzyme myeloperoxidase. This suggests a possible strategy for diminishing postoperative multiple-organ dysfunction. Copyright (c) 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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PMID: 20708753 [PubMed - as supplied by publisher]2: Shock. 2010 Mar;33(3):306-14.
Iwasaki W, Kume M, Kudo K, Uchinami H, Kikuchi I, Nakagawa Y, Yoshioka M, Yamamoto Y.
Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Prostanoids play a pivotal role among the inflammatory mediators associated with I/R injury. The aim of this study was to determine the effects of oral supplementation of n-3 polyunsaturated fatty acids (PUFA)-rich oil on inflammatory reactions and microcirculatory disorders caused by a hepatic warm I/R in rats. The rats were orally supplemented with n-3 PUFA-rich oil, n-6 PUFA-rich oil, or the same volume of water for 7 days. The PUFA concentration in the blood and liver tissues were evaluated, and the effects on I/R injury of the liver were assessed. The n-3 PUFA supplementation elevated the n-3/n-6 ratio in the blood and liver tissues. After reperfusion, thromboxane B(2) in the blood and prostaglandin E(2) in the liver were significantly suppressed in the n-3 PUFA-treated rats. Hepatic microcirculation was well maintained from the early phase (30 min) of reperfusion, and the serum concentrations of TNF-alpha and IL-6 were significantly lower in this group. The transaminase blood levels were also suppressed in the n-3 PUFA-treated rats. Expression of COX-2 mRNA was increased in all groups at 2 h after reperfusion but there were no differences among three groups. In conclusion, preoperative n-3/n-6 ratio augmentation in the blood and in the liver can result in a successful alleviation of hepatic I/R injury.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 19543146 [PubMed - indexed for MEDLINE]3: Klin Med (Mosk). 2009;87(4):37-41.
[Article in Russian]
Vasil'ev AP, Strel'tsova NN, Sekisova MA.
The aim of the study was to assess effect of omega-3 polyunsaturated fatty acids (PUFAs) on clinical manifestations of metabolic syndrome (MS) and microcirculation in patients with arterial hypertension (AH). 22 patients of the 32 with grade 2 AH and MC symptoms (by ATP III criteria) were given 1.5 mg of omega-3 PUFAs for 1 months. The control group comprised 10 patients. Serum lipid profile was detected and forearm skin microcirculation evaluated by laser Doppler flowmetry. Therapy with omega-3 PUFAs resulted in a significant decrease of serum triglycerides from 3.04 +/- 0.39 to 1.91 +/- 0.15 mmol/l (-37.2%). Its combination with hypotensive therapy reduced mean AP from 114.5 +/- 2.4 to 106.3 +/- 1.8 mm Hg (p < 0.01). Also, omega-3 PUFAs increased amplitude fluctuations in LDF-grams in endothelial and neurogenic ranges by 33.3 and 30.8% respectively, tissue hemoperfusion rate from 4.9 +/- 0.13 to 5.3 +/- 0.15 U (p < 0.05), capillary blood flow reserve by 13.7% (p < 0.05), maximum tissue hemoperfusion by 18.8% (p < 0.01), and coefficient of variation of tissue blood flow by 26.9%. Blood C-reactive protein level dropped by 40.7%. These changes were absent in control patients. It is concluded that correction of omega-3 PUFAs deficiency in patients with HA and MS reduces hyperlipidemia, has moderate antihypertensive effect, improves endothelial function and microcirculation. Multifunctional action of omega-3 PUFAs gives reason to recommend them for the treatment of MS.
Publication Types: English Abstract
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PMID: 19514319 [PubMed - indexed for MEDLINE]4: Curr Opin Anaesthesiol. 2009 Apr;22(2):177-83.
Weitzel LR, Mayles WJ, Sandoval PA, Wischmeyer PE.
Department of Anesthesiology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado 80045, USA. Lindsay.Weitzel@UCHSC.edu
PURPOSE OF REVIEW: A growing body of data has revealed that specific nutrient deficiencies contribute to microvascular and cellular dysfunction following critical illness. Further, targeted administration of these 'pharmaconutrients' may reverse or improve this dysfunction and improve clinical outcome. RECENT FINDINGS: Specific nutrient therapy with glutamine protects cellular metabolism and vascular function via induction of heat shock proteins, which are key proteins found to be deficient following acute illness. Arginine becomes rapidly deficient following trauma and surgery. This leads to significant immunosuppression, which when treated by arginine administration significantly reduces postoperative infection. Omega-3 fatty acids attenuate the inflammatory response and provide for resolution of ongoing inflammatory injury via production of resolvins/protectins. Antioxidants (vitamin C and selenium) and trace elements (zinc) become rapidly depleted in critical illness and replacement appears vital to ensure optimal cellular and microvascular function. Data on targeted metabolic (mitochondrial) therapies (i.e. co-enzyme Q10) show promise to improve myocardial function following cardiac surgery. SUMMARY: These specific nutrients have newly discovered vital mechanistic roles in the optimization of cellular and microcirculatory function in critical illness and injury. A growing body of literature is demonstrating that correction of key nutrient deficiencies via therapeutic administration of these pharmaconutrients can improve clinical outcome in critically ill patients.
Publication Types: Research Support, N.I.H., Extramural Review
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PMID: 19307892 [PubMed - indexed for MEDLINE]5: Diab Vasc Dis Res. 2008 Nov;5(4):319-35.
Fruchart JC, Sacks FM, Hermans MP, Assmann G, Brown WV, Ceska R, Chapman MJ, Dodson PM, Fioretto P, Ginsberg HN, Kadowaki T, Lablanche JM, Marx N, Plutzky J, Reiner Z, Rosenson RS, Staels B, Stock JK, Sy R, Wanner C, Zambon A, Zimmet P; Residual Risk Reduction Initiative (R3I).
Inserm UR 545, Universite Lille 2, Lille, France. Jean-Charles.Fruchart@pasteur-lille.fr
Despite current standards of care aimed at achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure and glycaemia, dyslipidaemic patients remain at high residual risk of vascular events. Atherogenic dyslipidaemia, specifically elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease, type 2 diabetes, obesity or metabolic syndrome and is associated with macrovascular and microvascular residual risk. The Residual Risk Reduction Initiative (R3I) was established to address this important issue. This position paper aims to highlight evidence that atherogenic dyslipidaemia contributes to residual macrovascular risk and microvascular complications despite current standards of care for dyslipidaemia and diabetes, and to recommend therapeutic intervention for reducing this, supported by evidence and expert consensus. Lifestyle modification is an important first step. Additionally, pharmacotherapy is often required. Adding niacin, a fibrate or omega-3 fatty acids to statin therapy improves achievement of all lipid risk factors. Outcomes studies are evaluating whether these strategies translate to greater clinical benefit than statin therapy alone. In conclusion, the R3I highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual vascular risk among dyslipidaemic patients who are treated in accordance with current standards of care.
Publication Types: Research Support, Non-U.S. Gov't Review
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PMID: 18958843 [PubMed - indexed for MEDLINE]6: Clin Sci (Lond). 2008 Jun;114(11):679-86.
Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM.
Hugh Sinclair Unit of Human Nutrition, Department of Food Biosciences, University of Reading, Reading RG6 6AP, UK.
Chronic fish oil intervention had been shown to have a positive impact on endothelial function. Although high-fat meals have often been associated with a loss of postprandial vascular reactivity, studies examining the effects of fish oil fatty acids on vascular function in the postprandial phase are limited. The aim of the present study was to examine the impact of the addition of fish oil fatty acids to a standard test meal on postprandial vascular reactivity. A total of 25 men received in a random order either a placebo oil meal (40 g of mixed fat; fatty acid profile representative of the U.K. diet) or a fish oil meal (31 g of mixed fat and 9 g of fish oil) on two occasions. Vascular reactivity was measured at baseline (0 h) and 4 h after the meal by laser Doppler iontophoresis, and blood samples were taken for the measurement of plasma lipids, total nitrite, glucose and insulin. eNOS (endothelial NO synthase) and NADPH oxidase gene expression were determined in endothelial cells after incubation with TRLs (triacylglycerol-rich lipoproteins) isolated from the plasma samples taken at 4 h. Compared with baseline, sodium nitroprusside (an endothelium-independent vasodilator)-induced reactivity (P=0.024) and plasma nitrite levels (P=0.001) were increased after the fish oil meal. In endothelial cells, postprandial TRLs isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene expression compared with TRLs isolated following the placebo oil meal (P</=0.03). In conclusion, meal fatty acids appear to be an important determinant of vascular reactivity, with fish oils significantly improving postprandial endothelium-independent vasodilation.
Publication Types: Randomized Controlled Trial
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PMID: 18052925 [PubMed - indexed for MEDLINE]7: J Hepatol. 2007 Nov;47(5):718-25. Epub 2007 Sep 14.
El-Badry AM, Graf R, Clavien PA.
Swiss HPB (Hepato-Pancreatico-Biliary) Centre, Department of Visceral and Transplant Surgery, University Hospital Zurich, Ramistrasse 100, CH-8091, Zurich, Switzerland.
Linoleic and alpha-linolenic acids are the fatty acids designated as "essential" since they are not synthesized by mammalian cells and must be provided in the diet. The recent dietary shift towards the consumption of n-6 (omega-6) at the expense of n-3 (omega-3) polyunsaturated fatty acids (PUFAs) is thought to be a primary cause of many diseases related to the Western diet. The body converts linoleic acid to arachidonic acid and derives eicosapentaenoic acid from alpha-linolenic acid. Ideally the effects of these fatty acids and their eicosanoid derivatives are tailored to the specific biological needs of the body. The balance between n-3 and n-6 PUFAs is essential for metabolism and maintenance of the functions of both classes. The availability of n-3 long chain PUFAs plays a major role in regulating both fat accumulation and its elimination by the liver. Derangement of hepatic n-6:n-3 PUFA ratio impacts on the histological pattern of fatty liver through modulation of the amount of intrahepatic lipids. Moreover, the influence of PUFAs and their eicosanoid products on hepatic microcirculation and ischemia/reperfusion injury has been demonstrated in many studies. This concise review article will focus on the role of PUFAs and eicosanoids in hepatic steatosis, microcirculation and ischemia/reperfusion injury.
Publication Types: Review
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PMID: 17869370 [PubMed - indexed for MEDLINE]8: Heart. 2008 Mar;94(3):316-21. Epub 2007 Jun 25.
Oe H, Hozumi T, Murata E, Matsuura H, Negishi K, Matsumura Y, Iwata S, Ogawa K, Sugioka K, Takemoto Y, Shimada K, Yoshiyama M, Ishikura Y, Kiso Y, Yoshikawa J.
Department of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan.
BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. OBJECTIVE: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). METHODS: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. RESULTS: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months' supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). CONCLUSION: Three months' supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.
Publication Types: Randomized Controlled Trial
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PMID: 17591648 [PubMed - indexed for MEDLINE]9: Hepatology. 2007 Apr;45(4):855-63.
El-Badry AM, Moritz W, Contaldo C, Tian Y, Graf R, Clavien PA.
Swiss HPB (Hepato-Pancreatico-Biliary) Centre, Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland.
Macrovesicular hepatic steatosis has a lower tolerance to reperfusion injury than microvesicular steatosis with an abnormally high ratio of omega-6 (n-6): omega-3 (n-3) polyunsaturated fatty acids (PUFAs). We investigated the influence of PUFAs on microcirculation in steatotic livers and the potential to minimize reperfusion injury in the macrosteatotic liver by normalization of PUFAs. Ob/ob mice were used as a model of macrovesicular hepatic steatosis and C57/Bl6 mice fed a choline-deficient diet for microvesicular steatosis. Steatotic and lean livers were subjected to 45 minutes of ischemia and 3 hours of reperfusion. Hepatic content of omega-3 and omega-6 PUFAs was determined. Microcirculation was investigated using intravital fluorescence microscopy. A second group of ob/ob mice was supplemented with dietary omega-3 PUFAs and compared with the control diet-fed group. Microcirculation, AST, and Kupffer cell activity were assessed. Macrosteatotic livers had significant microcirculatory dysfunction correlating with high omega-6: omega-3 PUFA ratio. Dietary omega-3 PUFA resulted in normalization of this ratio, reduction of intrahepatic lipids, and decrease in the extent of macrosteatosis. Defective microcirculation was dramatically ameliorated with significant reduction in Kupffer cell activity and protection against hepatocellular injury both before ischemia and after reperfusion. CONCLUSION: Macrosteatotic livers disclosed an abnormal omega-6: omega-3 PUFA ratio that correlates with a microcirculatory defect that enhanced reperfusion injury. Thus, protective strategies applied during or after ischemia are unlikely to be useful. Preoperative dietary omega-3 PUFAs protect macrosteatotic livers against reperfusion injury and might represent a valuable method to expand the live liver donor pool.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 17393510 [PubMed - indexed for MEDLINE]10: J Physiol Sci. 2007 Feb;57(1):43-9. Epub 2007 Jan 6.
Seki R, Okamura T, Ide T, Kage M, Sata M, Uyesaka N, Maruyama T.
Second Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, 830-0011, Japan.
Although erythrocyte filterability plays a key role in microcirculation, it is unknown whether the filterability of erythrocytes from patients with chronic hepatitis C (CH-C) is impaired. This study aimed to investigate erythrocyte filterability in CH-C patients in relation to medical treatment. The mean erythrocyte filterability (%) for all 24 patients with CH-C (69.2 +/- 10.8%) was significantly lower than that for 5 normal controls (80.5 +/- 1.7%, P < 0.03). In 8 patients, the combination therapy of ribavirin (RBV) and interferon improved liver function but caused anemia. The filterability after treatment (57.8 +/- 12.8%) was lower than that before treatment (70.8 +/- 9.7%, P < 0.05). Decreased filterability showed no correlation with the mean corpuscular volume or mean corpuscular Hb concentration during treatment, suggesting that the decrease in filterability mainly arises from changes in erythrocyte membrane properties. We investigated the protective effects of eicosapentaenoic acid (EPA) on the RBV-induced anemia. Filterability in 7 responders was markedly improved from 68.4 +/- 4.6% to 77.4 +/- 2.4% (P < 0.001), but not in 3 nonresponders. In the responders, the progression of anemia was restrained. In conclusion, we found an obvious impairment of the filterability of erythrocytes from CH-C patients, further impairment of the filterability induced by oxidative membrane damage caused by RBV leading to hemolytic anemia, and amelioration of the filterability caused by the antioxidative effects of EPA.
Publication Types: Controlled Clinical Trial Multicenter Study
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PMID: 17204208 [PubMed - indexed for MEDLINE]11: Prostaglandins Leukot Essent Fatty Acids. 2006 Mar;74(3):157-63. Epub 2006 Jan 10.
Ren H, Magulike N, Ghebremeskel K, Crawford M.
Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, North Campus, 166-220 Holloway Road, London N7 8DB, UK, and Department of Ophthalmology, University of Nigeria Teaching Hospital, Enugu, Nigeria. Hor016@londonmet.ac.uk
The aetiology of primary open-angle glaucoma (POAG), which is the commonest cause of non-remediable blindness and visual impairment, is not well understood. Nevertheless, increased intraocular pressure, and vascular factors such as ocular blood flow deficits are thought to be risk factors. There is evidence of decreased optic nerve blood velocity and increased red blood cell aggregability in POAG. These factors are influenced by fatty acids. We have investigated if glaucoma patients have abnormal blood fatty acid composition. Patients with POAG (n=10) and their healthy siblings (n=8) were enrolled. Compared with their healthy siblings, the glaucoma patients had reduced eicosapentaenoic (EPA, P<0.01), and docosahexaenoic (DHA, P<0.05) fatty acids and total omega3 long-chain polyunsaturated fatty acids (LCPUFA) (P<0.05) in red cell choline phosphoglycerides (CPG); decreased EPA (P<0.05) in ethanolamine phosphoglycerides (EPG); lower EPA (P<0.05) and total omega3 LCPUFA (P<0.05) in serine phosphoglycerides (SPG). Similarly, they had reduced EPA, DHA and total omega3 LCPUFA in plasma CPG (P<0.005) and triglycerides (P<0.05). These findings may be significant, since EPA and DHA could modulate impaired systemic microcirculation and ocular blood flow and optic neuropathy, which are the main physiological changes associated with glaucoma.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 16410047 [PubMed - indexed for MEDLINE]12: J Nutr. 2005 Sep;135(9):2241-6.
Pifferi F, Roux F, Langelier B, Alessandri JM, Vancassel S, Jouin M, Lavialle M, Guesnet P.
Nutrition and Food Safety Laboratory Unit, Neurobiology of Lipids, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, 78352 Cedex, France. fabien.pifferi@jouy.inra.fr
The altered neuron activity of rats deficient in (n-3) PUFAs may be due in part to a decrease in brain glucose utilization and glucose transport. We measured the glucose transporter protein GLUT1 isoforms at the blood-brain barrier (55-kDa) and in astrocytes (45-kDa) by Western immunoblotting and their mRNA by real time RT-PCR analysis in the cerebral cortex of adult male rats fed diets lacking (n-3) fatty acids (1st generation). The neuron glucose transporter GLUT3 was also assayed. The fatty acids in the phosphatidylcholine (PC), ethanolamine phosphoglycerolipid (EPG), and phosphatidylserine (PS) fractions of isolated microvessels and homogenates of the cerebral cortex were determined. The levels of (n-6) PUFAs [mainly arachidonic acid, 20:4(n-6)] in the phospholipid fractions of microvessels were higher and the levels of (n-3) PUFAs [mainly docosahexaenoic acid, 22:6(n-3)] were lower than in cerebral cortex homogenates. The microvessels and cortex of rats fed the (n-3) PUFA-deficient diet had 50% of the control 22:6(n-3) contents; 22:6(n-3) was replaced by 22:5(n-6). The 55-kDa GLUT1 immunoreactivity in (n-3) PUFA-deficient microvessels was decreased (down 25%, P < 0.01), as was the 45 kDa-GLUT1 in the homogenate (down 30%, P < 0.01). But the amount of immunoreactivity of GLUT3 did not change. The amount of GLUT1 mRNA was not affected by the (n-3) PUFA-deficient diet. These results suggest that the decreased glucose utilization in the cerebral cortex of (n-3) PUFA-deficient rats is due to reduced amounts of the 2 isoforms of GLUT1, indicating post-transcriptional regulation of GLUT1 synthesis.
Publication Types: In Vitro Research Support, Non-U.S. Gov't
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PMID: 16140905 [PubMed - indexed for MEDLINE]13: Prostaglandins Leukot Essent Fatty Acids. 2005 May;72(5):335-41.
Thomas BA, Ghebremeskel K, Lowy C, Offley-Shore B, Crawford MA.
Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, TB 9/4, 166-220 Holloway Road, London N7 8DB, UK. thomasb@unl.ac.uk
Women with gestational diabetes mellitus (GDM) and their neonates have lower levels of arachidonic (AA) and docosahexaenoic (DHA) acids in red cell membranes. It is not clear if this abnormality is restricted to red cells or is a generalised problem. We have investigated plasma fatty acids of neonates (venous cord) of GDM (n=37), and non-diabetic (n=31) women. The GDMs had lower levels of dihomogamma-linolenic (20:3n-6, DHGLA) acid, summation operator n-6 metabolites, DHA and summation operator n-3 metabolites (p<0.05) in choline phosphoglycerides (CPG). They also had lower levels of AA (-4.5%), adrenic acid (22:4n-6, -13%), osbond acid (22:5n-6, -7%) and summation operator n-6 (-2.5%). There was a similar pattern in triglycerides (TG) and cholesterol esters (CE). Mead acid, a marker of generalised shortage of derived and parent essential fatty acids, was higher in CPG and TG of the GDM group by 73% and 76%. The adrenic/osbond acid (22:4n-6/22:5n-6) ratio, a biochemical marker of DHA insufficiency, was reduced in CPG (-4.5%), TG (-63%) and CE (-75%) of the GDM group. These findings, which are consistent with the previous red cell data, suggest that the neuro-visual and vascular development and function of the offspring of GDM women may be adversely affected if the levels of AA and DHA are compromised further by other factors, pre- or post-natally. Studies are required to elucidate the underlying mechanism for the reduction of the two fatty acids and to evaluate the developmental and health implications.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=15850714&dopt=ExternalLink
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PMID: 15850714 [PubMed - indexed for MEDLINE]14: Cell Mol Biol (Noisy-le-grand). 2004 Nov;50(7):845-53.
Coste TC, Gerbi A, Vague P, Maixent JM, Pieroni G, Raccah D.
UPRES EA2193, 27 Boulevard Jean Moulin, 13385 Marseille, France. thierry.coste@medecine.univ-mrs.fr
The two essential fatty acids linoleic and alpha-linolenic acids, precursors of the n-6 and n-3 PUFA family, respectively, are known to play a strong regulatory function on cells via their incorporation into membrane phospholipids, and also on microcirculation by the production of eicosanoids. Moreover, diabetes mellitus induces impairment in PUFA metabolism due to an inhibition of desaturases, the enzymes involved in their synthesis. The decrease in PUFA bioavailability will conduct to marked alterations in membranes as well as impairment of the microcirculation. Those metabolic perturbations are involved in part in the degenerative complications of diabetes such as neuropathy. Nutritional supplementations with PUFA have given very interesting results in experimental diabetic neuropathy but also in human diabetic neuropathy. The gamma linolenic and arachidonic acids, members of the n-6 family, prevent the physiological abnormalities associated to neuropathy. The results obtained with the n-3 family PUFA are more discordant, probably because of the simultaneous use of eicosapentaenoic and docosahexaenoic acids. Nevertheless, the use of docosahexaenoic acid-enriched phospholipids produced positive results in the treatment of experimental diabetic neuropathy. These PUFA are available from natural sources but a biotechnological demand exists to provide these PUFA in different structural forms.
Publication Types: Review
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PMID: 15672469 [PubMed - indexed for MEDLINE]15: Prostaglandins Leukot Essent Fatty Acids. 2003 Jul;69(1):33-7.
Shimizu T, Suzuki M, Lee T, Igarashi J, Kaneko K, Yamashiro Y.
Department of Pediatrics, School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. tsimizut@aol.com
We investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on non-steroidal anti-inflammatory drug (NSAID)-induced changes in microcirculation and eicosanoid production in the gastrointestinal mucosa. We measured gastric mucosal blood flow using laser Doppler flowmetry, assessed the fatty acid composition in the mucosal phospholipids, and quantified the production of prostaglandin E2 (PGE2), leukotriene B4, and leukotriene C4 (LTB4 and C4) from the mucosa with the stimulation of calcium ionophore 20 min after an injection of indomethacin or vehicle in rats fed a diet containing different compositions of alpha-linolenic acid. Four weeks after the initiation of the test diet the arachidonic acid level in gastric mucosal phospholipids was significantly lower in the perilla group than in the other three groups. Conversely, alpha-linolenic acid and eicosapentaenoic acid (EPA) were significantly higher in the perilla group than in the other three groups. The percent of gastric mucosal blood flow in the three groups administered indomethacin were significantly lower than that in the control group injected with vehicle alone. The percent of gastric mucosal blood flow in the perilla group was significantly higher than that in the corn group. LTB4 and LTC4 production from the gastric mucosa in the soybean and corn groups were significantly higher than those in the control group, and the LTC4 production in the perilla group was significantly lower than that in the corn group. There were no significant differences in PGE2 production among the four groups. Our results suggest that alpha-linolenic acid affectively suppressed the indomethacin-induced decreases in gastric mucosal blood flow by increasing EPA and decreasing the levels of arachidonic acid and LTC4 in the gastric mucosa.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=12878448&dopt=ExternalLink
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PMID: 12878448 [PubMed - indexed for MEDLINE]16: Arch Dis Child Fetal Neonatal Ed. 2003 Mar;88(2):F134-8.
McFadyen M, Farquharson J, Cockburn F.
University Department of Child Health, Royal Hospital for Sick Children and Queen Mother's Hospital, Yorkhill NHS Trust, Glasgow G3 8SJ, Scotland, UK.
BACKGROUND: Being devoid of both nuclei and mitochondria, mature human erythrocytes provide an opportunity to study membrane structure and function outwith the restrictions of genetic control. With its unique rapid increase in vascularisation, pregnancy is considered the most opportune period in which to investigate blood rheology. METHODS: Maternal and fetal (cord) bloods were retained at delivery from 32 (25 singleton and seven twin) normal pregnancies at two maternity hospitals in the Glasgow area over a nine month period. Erythrocyte fatty acid compositions were assessed by mass spectroscopy, and corresponding membrane deformabilities measured by ultrafiltration through a membrane of 5 micro m diameter pore size, to mimic placental microcirculation. RESULTS: Significant direct correlations (Spearman rank) were found between erythrocyte membrane omega-3 docosahexaenoic acid concentrations and corresponding deformabilities in maternal and cord blood from both singleton and twin pregnancies, whereas greater omega-6 arachidonic acid content was associated with increased maternal membrane rigidity. Membrane concentrations of omega-3 fatty acids only correlated strongly both within and between maternal and cord bloods. Mean cord erythrocyte docosahexaenoic acid concentration was higher than maternal in singletons but lower in twins. When maternal erythrocyte concentrations exceeded about 7% (of total fatty acids), resistance to erythrocyte flow was virtually eliminated. CONCLUSIONS: It may be that a greater maternal intake of docosahexaenoic acid should be encouraged in some pregnancies for optimal tissue perfusion. Fetal demand for docosahexaenoic acid may not be entirely satisfied in multiple pregnancies.
Publication Types: Multicenter Study
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=12598503&dopt=ExternalLink
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PMID: 12598503 [PubMed - indexed for MEDLINE]17: Crit Care Med. 2002 May;30(5):1091-8.
Vollmar B, Bauer C, Menger MD.
Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
OBJECTIVE: We investigated the potential of dietary fish oil containing n-3 polyunsaturated fatty acids to attenuate hepatic injury and mortality rate of rats in response to systemic endotoxemia. DESIGN: Prospective, randomized, controlled animal study. SETTING: University laboratory. SUBJECTS: A total of 43 male Sprague Dawley rats. INTERVENTIONS: Rats were fed either fish oil supplement or regular standard lab chow. After 8 wks of feeding, each diet group was subjected to a single exposure of lipopolysaccharide (Escherichia coli, 10 mg/kg intravenously) or saline. Hepatic microvascular response and liver injury were assessed by in vivo analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction, nutritive sinusoidal perfusion failure, and parenchymal cell apoptosis (intravital fluorescence epi-illumination technique) as well as bile flow, serum liver enzyme activities, and tissue histomorphology. MEASUREMENTS AND MAIN RESULTS: In animals fed a standard diet, livers at 16 hrs after lipopolysaccharide-exposure exhibited depressed Kupffer cell phagocytic activity, enhanced hepatic microvascular leukocyte activation, leukocytic tissue infiltration, sinusoidal perfusion failure, and parenchymal cell apoptosis. Hepatic microvascular injury was further accompanied by reduced bile flow and enhanced liver enzyme release. The fish oil enriched diet did not significantly change the multiple features of endotoxemia-associated liver injury; however, it maintained arterial blood pressure, systemic leukocyte count, and acid base balance and showed a tendency toward improved survival on lipopolysaccharide exposure with a 16 hr-survival rate of 80% (p =.06 vs. survival rate of 40% in animals fed a regular diet). Moreover, slightly increased serum concentrations of interleukin-10 coincided with enhanced concentrations of interleukin-6 in fish oil fed endotoxemic animals. Healthy, non-lipopolysaccharide-exposed, fish oil fed animals did not differ from those fed with the regular diet, except for dampened Kupffer cell phagocytic activity. CONCLUSIONS: Fish oil feeding does not protect from local endotoxemia-induced hepatic microvascular dysfunction. However, dietary modulation of inflammatory mediator response by macrophages, constituting an appropriate immune response, could add to the survival advantage seen in fish oil-fed animals on exposure to lipopolysaccharide.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=12006807&dopt=ExternalLink
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PMID: 12006807 [PubMed - indexed for MEDLINE]18: Int J Vitam Nutr Res. 2001 Sep;71(5):286-92.
Min Y, Ghebremeskel K, Crawford MA, Nam JH, Kim A, Lee IS, Suzuki H.
Institute of Brain Chemistry and Human Nutrition, University of North London, London N7 8DB, UK.
Fatty acid distribution was investigated in ethnically and economically homogenous Korean mothers (n = 40) and neonates. Venous blood, maternal before delivery and cord, was obtained. Choline (CPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SM) were assayed. Mean arachidonic acid (AA) level was higher in plasma CPG and SM (p < 0.0001), and red cell CPG (p < 0.0001), EPG (p < 0.0001) and SM (p = 0.005) of the neonates. Similarly, the neonates had higher proportions of docosahexaenoic acid (DHA) in plasma CPG (p < 0.0001) and red cell CPG (p = 0.001) and EPG (p = 0.036). In contrast, linoleic and alpha-linolenic acids were significantly higher in maternal blood. Mead acid was elevated in plasma CPG (p < 0.0001) and red cell CPG and EPG (p < 0.0001) of the neonates. Consistent with data from high-fat-intake populations, our subjects, whose traditional diet is low in fat, exhibited maternal-fetal gradient in AA and DHA in plasma and red cell phospholipids. This may be due to an imbalance between supply and maternal and fetal requirements, and/or a physiological response to pregnancy. Prenatal nutritional constraint is associated with impaired development and a risk of chronic diseases in adults. AA and DHA are vital nutrients. Hence, there is a need to investigate whether the discrepancy between maternal and neonatal AA and DHA is a manifestation of nutritional insufficiency.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11725693&dopt=ExternalLink
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PMID: 11725693 [PubMed - indexed for MEDLINE]19: In Vitro Cell Dev Biol Anim. 2001 Oct;37(9):618-23.
Hostmark AT, Lystad E.
Section of Preventive Medicine and Epidemiology, University of Oslo, Norway. a.t.hostmark@samfunnsmed.uio.no
Peroxidation products of polyunsaturated fatty acids may cause growth inhibition of cells in culture. This study was carried out to elucidate to what extent peroxidation products may be found in growth media, with and without cells and albumin, using thiobarbituric acid-reactive substances (TBARS) and protein carbonyl groups as measures of peroxidation. The growth of human microvascular endothelial cells was studied as influenced by docosahexaenoic (C22:6, n - 3), arachidonic acid (C20:4. n - 6), and serum albumin. Cell growth was strongly inhibited by the fatty acids, and the inhibition was related to the concentration of TBARS in the medium. Defatted albumin (0.5 g/100 ml) nullified the increase of TBARS in the medium and released the growth inhibition by the fatty acids. With polyunsaturated fatty acids (PUFA) there was a time- and concentration-dependent increase in media TBARS, observed both with and without cells, but the TBARS increase was somewhat greater in the presence of cells. Surprisingly, TBARS in cell-free media also increased somewhat upon increasing the albumin concentration from 0.5 to 5 g/100 ml, and the TBARS increase differed among various preparations of albumin. Unexpectedly, the albumin that had not been defatted gave the lowest TBARS values. The amount of protein carbonyl groups did not differ among various albumin preparations. It is concluded that PUFA may autooxidize in media used for cell cultures, and thereby cause an unspecific growth inhibition, which can be prevented by a low albumin concentration. However, even defatted albumin preparations may contain lipid peroxidation products, the causes and implications of which remain to be elucidated.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11710440&dopt=ExternalLink
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PMID: 11710440 [PubMed - indexed for MEDLINE]20: Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2430-40.
Zhang Y, Oltman CL, Lu T, Lee HC, Dellsperger KC, VanRollins M.
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242, USA.
Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated the structural specificity of EETs in dilating canine and porcine coronary microvessels (50-140 microm ID) and activating large-conductance Ca2+-activated K+ (BK(Ca)) channels. The potencies and efficacies of EET regioisomers and enantiomers were compared with those of two EET homologs: epoxyeicosaquatraenoic acids (EEQs), which are made from eicosapentaenoic acid by the same cytochrome P-450 epoxygenase that generates EETs from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With EC50 values of 3-120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine microvessels. Surprisingly, the EEQs and EDTs had comparable potencies and efficacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BK(Ca) channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BK(Ca) channels possess low structural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyperpolarizing factors.
Publication Types: In Vitro Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11356595&dopt=ExternalLink
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PMID: 11356595 [PubMed - indexed for MEDLINE]