Effects of DHA- Rich n-3 Fatty Acid Supplementation on Gene Expression in Blood Mononuclear Leukocytes: The OmegAD Study

Background: Dietary fish oil, rich in n-3 fatty acids (n-3 FAs), e. g. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), regulate inflammatory reactions by various mechanisms, e. g. gene activation. However, the effects of long-term treatment with DHA and EPA in humans, using genome wide techniques, are poorly described. Hence, our aim was to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells. Methods and Findings: In the present study, blood samples were obtained from a subgroup of 16 patients originating from the randomized double-blind, placebo-controlled OmegAD study, where 174 Alzheimer disease (AD) patients received daily either 1.7 g of DHA and 0.6 g EPA or placebo for 6 months. In blood samples obtained from 11 patients receiving n-3 FA and five placebo, expressions of approximately 8000 genes were assessed by gene array. Significant changes were confirmed by real-time PCR. At 6 months, the n-3 FAs group displayed significant rises of DHA and EPA plasma concentrations, as well as up-and down-regulation of nine and ten genes, respectively, was noticed. Many of these genes are involved in inflammation regulation and neurodegeneration, e. g. CD63, MAN2A1, CASP4, LOC399491, NAIP, and SORL1 and in ubiqutination processes, e. g. ANAPC5 and UBE2V1. Down-regulations of ANAPC5 and RHOB correlated to increases of plasma DHA and EPA levels. Conclusions: We suggest that 6 months of dietary n-3 FA supplementatio

The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production

Abstract Innate defense mechanisms are aimed at quickly containing and removing infectious microorganisms and involve local stromal and immune cell activation, neutrophil recruitment and activation and the induction of host defense peptides (defensins and cathelicidins), acute phase proteins and complement activation. As an alternative to antibiotics, innate immune mechanisms are highly relevant as they offer rapid general ways to, at least partially, protect against infections and enable the build-up of a sufficient adaptive immune response. This review describes two classes of promising alternatives to antibiotics based on components of the innate host defense. First we describe immunoglobulins applied to mimic the way in which they work in the newborn as locally acting broadly active defense molecules enforcing innate immunity barriers. Secondly, the potential of host defense peptides with different modes of action, used directly, induced in situ or used as vaccine adjuvants is described

Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation

Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12±1 g day−1) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20 : 4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20 : 4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Serious complications of urinary tract infection in diabetes: emphysematous pyelonephritis and endogenous endophthalmitis

Introduction Severe infectious complications may occur in poorly regulated diabetic patients. In most cases treatment will lead to full recovery. Here we describe a patient with urosepsis complicated by emphysematous pyelonephritis (EPN) and endogenous endophthalmitis. Case description A 42-year-old woman with uncontrolled diabetes presented with a ketoacidosis and right flank pain due to an urosepsis with Escherichia coli (E. coli). Ultrasonography and CT scan of the abdomen showed features of emphysematous pyelonephritis of the right kidney with gas in the renal parenchyma. Subsequently the patient complained of pain and photophobia of the left eye, diagnosed as an endogenous endophthalmitis with a cloudy cornea, hypopyon en loss of details of the iris. Confirmation of the diagnosis and treatment consisted of vitrectomy of the left eye, silicone oil injection and intravitreal antibiotics. E. coli was isolated from the vitreous fluid. Pyelonephritis was treated with systemic antibiotics and percutaneous drainage. Patient follow up learned that she had no light perception of the left eye and a non- functional right kidney. Conclusion Both endogenous endophthalmitis and emphysematous pyelonephritis are rare complications of infection, which are sight- and lifethreatening. Treatment of endogenous endophthalmitis comprises both intravitreal and systemic therapy and has a poor visual prognosis despite aggressive therapy. Treatment of EPN consists of antibiotic therapy, early percutaneous drainage and nephrectomy when indicated. With the increasing number of diabetics we should be aware of the occurrence of rare infectious complications

Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial state

BACKGROUND: In obese subjects, chronic low-grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti-inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention. MATERIAL AND METHODS: Eleven obese men (BMI: 30-35 kg m(-2)) received daily fish oil (1.35 g n-3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9.4 kg. At the end of each experimental period a postprandial study was performed. RESULTS: Relative to fasting concentrations, interleukin-6 (IL-6) levels increased by 75% 2 h and by 118% 4 h after the meal (P < 0.001), when subjects consumed the control capsules. In contrast, C-reactive protein (C-RP) concentrations decreased slightly by 0.7% and 6.6% (P = 0.046), and those of plasminogen activator inhibitor-1 (PAI-1) antigen by, respectively, 26% and 53% (P < 0.001). Tumour necrosis factor-alpha (TNF-alpha; P = 0.330) and soluble TNF-receptor concentrations (sTNF-R55 and sTNF-R75; P = 0.451 and P = 0.108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL-6, C-RP, sTNF-R55, sTNF-R75, and PAI-1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. CONCLUSION: For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction