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    Polyunsaturated acids and inflammation: therapeutic potential in rheumatoid arthritis

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    The fatty acids of most relevance to inflammatory processes are the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid, the precursor of inflammatory eicosanoids like prostaglandin E2 and leukotriene B4, and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in rheumatoid arthritis (RA), and the efficacy of nonsteroidal antiinflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. N- 3 PUFAs exert effects on other aspects of immunity relevant to RA like leukocyte chemotaxis, antigen presentation, T cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits of fish oil in patients with RA including reducing pain, duration of morning stiffness and use of non-steroidal antiinflammatory drugs

    Rationale and use of n-3 fatty acids in artificial nutrition

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    Lipids traditionally used in artificial nutrition are based on n-6 fatty acid-rich vegetable oils like soyabean oil. This may not be optimal because it may present an excessive supply of linoleic acid. One alternative to the use of soyabean oil is its partial replacement by fish oil, which contains n-3 fatty acids. These fatty acids influence inflammatory and immune responses and so may be useful in particular situations where those responses are not optimal. Fish oil-containing lipid emulsions have been used in parenteral nutrition in adult patients post-surgery (mainly gastrointestinal). This has been associated with alterations in patterns of inflammatory mediators and in immune function and, in some studies, a reduction in length of intensive care unit (ICU) and hospital stay. Perioperative administration of fish oil may be superior to post-operative. Parenteral fish oil has been used in critically ill adults. Here the influence on inflammatory processes, immune function and clinical endpoints is not clear, since there are too few studies and those that are available report contradictory findings. Fish oil is included in combination with other nutrients in various enteral formulas. In post-surgical patients and in those with mild sepsis or trauma, there is clinical benefit from a formula including fish oil and arginine. A formula including fish oil, borage oil and antioxidants has demonstrated marked benefits on gas exchange, ventilation requirement, new organ failures, ICU stay and mortality in patients with acute respiratory distress syndrome, acute lung injury or severe sepsis

    Fatty acids and immune function: relevance to inflammatory bowel diseases

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    Fatty acids may influence immune function through a variety of mechanisms; manyof these are associated with changes in fatty acid composition of immune cell membranes.Eicosanoids produced from arachidonic acid have roles in inflammationand immunity. Increased membrane content of n-3 fatty acids results in a changedpattern of production of eicosanoids, resolvins, and cytokines. Changing the fattyacid composition of immune cells also affects T cell reactivity and antigen presentation.Little attention has been paid to the influence of fatty acids on the gutassociatedlymphoid tissue. However, there has been considerable interest in fatty acids and gut inflammatio

    The effect of three lipid emulsions differing in fatty acid composition on growth, apoptosis and cell cycle arrest in the HT-29 colorectal cancer cell line

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    Background &amp; aims: An in vitro study showed that a lipid emulsion containing fish oil (FO) slows the growth of colon cancer cells and enhances their sensitivity to 5-fluorouracil (FU). The aim was to confirm this finding and to compare such an emulsion with an alternative to lowered n-6 fatty acid exposure.Methods: We determined the number of viable cells, apoptosis and cell cycle distribution of HT-29 cells after exposure to one of three lipid emulsions. Cell cycle distribution was also assessed after treatment with lipid emulsions and FU.Results: The lipid emulsion containing FO induced a significant growth inhibitory effect without changing the percentage of apoptotic cells. Exposure to the other lipid emulsions had no effect on growth and decreased apoptosis. Each lipid emulsion potentiated the S phase-halting effect of 1 and 10 ?M FU. This effect also occurred at 0.1 ?M FU when the cells were exposed to the FO containing lipid emulsion.Conclusions: A lipid emulsion containing FO has a growth inhibitory effect on a human colon adenocarcinoma cell line, an effect not due to the induction of apoptosis, and potentiated the S phase-halting effect of FU. Thus, an FO lipid emulsion may be of benefit in colorectal cancer.<br/

    Effects of a fish oil containing lipid emulsion on plasma phospholipid fatty acids, inflammatory markers, and clinical outcomes in septic patients: a randomized, controlled clinical trial

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    Introduction: the effect of parenteral fish oil in septic patients is not widely studied. This study investigated the effects of parenteral fish oil on plasma phospholipid fatty acids, inflammatory mediators, and clinical outcomes.Methods: twenty-five patients with systemic inflammatory response syndrome or sepsis, and predicted to need parenteral nutrition were randomized to receive either a 50:50 mixture of medium-chain fatty acids and soybean oil or a 50:40:10 mixture of medium-chain fatty acids, soybean oil and fish oil. Parenteral nutrition was administrated continuously for five days from admission. Cytokines and eicosanoids were measured in plasma and in lipopolysaccharide-stimulated whole blood culture supernatants. Fatty acids were measured in plasma phosphatidylcholine.Results: fish oil increased eicosapentaenoic acid in plasma phosphatidylcholine (P &lt;0.001). Plasma interleukin (IL)-6 concentration decreased significantly more, and IL-10 significantly less, in the fish oil group (both P &lt;0.001). At Day 6 the ratio PO2/FiO2 was significantly higher in the fish oil group (P = 0.047) and there were fewer patients with PO2/FiO2 &lt;200 and &lt;300 in the fish oil group (P = 0.001 and P = 0.015, respectively). Days of ventilation, length of intensive care unit (ICU) stay and mortality were not different between the two groups. The fish oil group tended to have a shorter length of hospital stay (22 ± 7 vs. 55 ± 16 days; P = 0.079) which became significant (28 ± 9 vs. 82 ± 19 days; P = 0.044) when only surviving patients were included.Conclusions: inclusion of fish oil in parenteral nutrition provided to septic ICU patients increases plasma eicosapentaenoic acid, modifies inflammatory cytokine concentrations and improves gas exchange. These changes are associated with a tendency towards shorter length of hospital stay.Clinical Trials Registration Number ISRCTN8943294

    Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions

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    Background: Energy deficit is a common and serious problem in intensive care units and is associated with increased rates of complications, length of stay, and mortality. Parenteral nutrition (PN), either alone or in combination with enteral nutrition, can improve nutrient delivery to critically ill patients. Lipids provide a key source of calories within PN formulations, preventing or correcting energy deficits and improving outcomes. Discussion: In this article, we review the role of parenteral lipid emulsions (LEs) in the management of critically ill patients and highlight important biologic activities associated with lipids. Soybean-oil-based LEs with high contents of polyunsaturated fatty acids (PUFA) were the first widely used formulations in the intensive care setting. However, they may be associated with increased rates of infection and lipid peroxidation, which can exacerbate oxidative stress. More recently developed parenteral LEs employ partial substitution of soybean oil with oils providing medium-chain triglycerides, ?-9 monounsaturated fatty acids or ?-3 PUFA. Many of these LEs have demonstrated reduced effects on oxidative stress, immune responses, and inflammation. However, the effects of these LEs on clinical outcomes have not been extensively evaluated. Conclusions: Ongoing research using adequately designed and well-controlled studies that characterize the biologic properties of LEs should assist clinicians in selecting LEs within the critical care setting. Prescription of PN containing LEs should be based on available clinical data, while considering the individual patient’s physiologic profile and therapeutic requirements. <br/
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