The development of an ELISA for group IVA phospholipase A2 in human red blood cells.

An immunoassay for IVA phospholipase A2 in human red blood cells is described. The assay is a non-competitive sandwich assay in which increasing amounts of the measured protein produce increased luminescence. The antibodies used in the assay are directed against two unique epitopes of the molecule, which sequentially trap and detect the protein.

Long-chain polyunsaturated fatty acids modulate interleukin-1beta-induced changes in behavior, monoaminergic neurotransmitters, and brain inflammation in rats.

Recent evidence has suggested that an imbalance between membrane (n-3) and (n-6) fatty acids may contribute to the etiology of autoimmune and neurodegenerative diseases. In this study, the mechanisms by which eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and arachidonic acid (AA) modulate neurotransmitters, behavior, and brain inflammation were evaluated in rats that received central saline or interleukin-1beta (IL-1) administrations. In rats treated with saline, only the AA-enriched diet significantly increased anxiety-like behavior in the elevated plus maze, which was associated with increased corticosterone secretion.

Fish consumption and depression: the Northern Finland 1966 birth cohort study.

Background: Since low fish consumption and omega-3 fatty acids have recently been linked with depression, we investigated by means of a large, general population database, whether a low fish consumption is associated with increased risk of developing depression.

Methods: The Northern Finland 1966 Birth Cohort was followed up prospectively from pregnancy up to the age of 31 years. The data on HSCL-25 depression subscale, doctor-diagnosed life-time depression and fish consumption (during the previous 6 months) of cohort members were obtained by postal questionnaires at the age of 31.

Ethyl-EPA in Alzheimer's disease--a pilot study.

This pilot study of ethyl-eicosapentaenoate (ethyl-EPA) in the treatment of Alzheimer's disease aimed to estimate the magnitude of any change in measures of cognition during a 12-week treatment period. A simple linear design was used in which each patient had a baseline period of 12 weeks without treatment, followed by 12 weeks' treatment with ethyl-EPA. Blood samples were taken both before and after the treatment period to measure erythrocyte membrane fatty acids.

Neuroprotective actions of eicosapentaenoic acid on lipopolysaccharide-induced dysfunction in rat hippocampus.

Eicosapentaenoic acid (EPA) protects hippocampus from age-related and irradiation-induced changes that lead to impairment in synaptic function; the evidence suggests that this is due to its anti-inflammatory effects, specifically preventing changes induced by the proinflammatory cytokine, interleukin-1beta (IL-1beta). In this study, we have investigated the possibility that EPA may prevent the effects of lipopolysaccharide (LPS) administration, which have been shown to lead to deterioration of synaptic function in rat hippocampus. The data indicate that treatment of hippocampal neurones with EPA abrogated the LPS-induced increases in phosphorylation of the mitogen-activated protein kinase, c-Jun N-terminal kinase (JNK), the transcription factor, c-Jun and the mitochondrial protein, Bcl-2.

A pilot open case series of ethyl-EPA supplementation in the treatment of anorexia nervosa.

Anorexia nervosa (AN) carries the highest risk of morbidity and mortality amongst psychiatric disorders. The efficacy of current treatment approaches is limited. Despite the fat-phobic nature of the disease, poly-unsaturated fatty acids (PUFAs) have not received much research attention.

Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats.

Omega (n)-3 and n-6 fatty acids are important membrane components of neurons and immune cells, and related to psychiatric and inflammatory diseases. Increased ratio of n-6/n-3 in the blood has been reported in depressed patients and in students following stress exposure. The n-3 fatty acid, eicosapentaenoic acid (ethyl-EPA) suppresses inflammation and has antidepressant properties.

Omega-3 fatty acid ethyl-eicosapentaenoate, but not soybean oil, attenuates memory impairment induced by central IL-1beta administration.

Proinflammatory cytokine interleukin (IL)-1beta can cause cognitive impairment, activate the hypothalamic-pituitary-adrenal axis and impair monoaminergic neurotransmission in the rat. IL-1beta has also been shown to increase the concentration of the inflammatory mediator prostaglandin E2 (PGE2) in the blood. Omega (n)-3 fatty acids, such as eicosapentaenoic acid (EPA), which are components of fish oil, have been shown to reduce both the proinflammatory cytokines and the synthesis of PGE2.

Ethyl-eicosapentaenoate and dexamethasone resistance in therapy-refractory depression.

Preliminary evidence shows that ethyl-eicosapentaenoate (E-EPA) has a marked clinical effect when used as an adjunct in therapy-refractory depression. EPA belongs to the class of polyunsaturated omega-3 fatty acids. The mechanism of its action in depression is not fully understood.

Cytosolic phospholipase A2 type IVA is present in human red cells.

Phospholipase A(2) type IVA (IVAPLA(2)) is a cytosolic enzyme that on activation selectively releases arachidonic acid (AA) from cell membrane phospholipids. Both AA and lysophospholipid, products of the enzymic reaction, can function as signal transducers in cellular interactions. The enzyme is present in most cells, including polymorphs, eosinophils, and platelets.

Degradation of specific polyunsaturated fatty acids in red blood cells stored at -20 degrees C proceeds faster in patients with schizophrenia when compared with healthy controls.

Deficits in red blood cell (RBC) polyunsaturated fatty acids (PUFAs) have been extensively reported in schizophrenia although reports are inconsistent. A possible explanation for this inconsistency is varying storage conditions of blood samples prior to analysis, especially freezer storage temperature. We conducted a prospective investigation of fatty acid degradation rates in RBCs from healthy control subjects when samples from each individual were stored at both -20 degrees C or -70 degrees C.

Effects of dietary n-3 or n-6 fatty acids on interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats.

The present study demonstrated that an omega (n)-3 fatty acid, ethyl-eicosapentaenoic acid (ethyl-EPA), supplemented diet significantly attenuated the stress/anxiety behavior of rats in the "open field" and elevated plus maze, which was induced by subchronic intracerebroventricular administration of proinflammatory cytokine interleukin (IL)-1beta. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-gamma-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration.

The effects on plasma, red cell and platelet fatty acids of taking 12 g/day of ethyl-eicosapentaenoate for 16 months: dihomogammalinolenic, arachidonic and docosahexaenoic acids and relevance to Inuit metabolism.

A patient with mantle cell lymphoma took 12g/day of ethyl-eicosapentaenoate for 16 months. Compared to reference values, eicosapentaenoic and docosapentaenoic acids were elevated in plasma, red cells and platelets but docosahexaenoic acid levels were in the normal range. Arachidonic acid levels were moderately reduced but dihomogammalinolenic acid levels remained in the normal range.

A low toxicity maintenance regime, using eicosapentaenoic acid and readily available drugs, for mantle cell lymphoma and other malignancies with excess cyclin D1 levels.

Mantle cell lymphoma is a difficult to treat non-Hodgkin's lymphoma (NHL) whose biochemistry is unusually well characterised. Almost all and perhaps all patients overexpress the cyclin D1 protein which is crucial in driving cells from the G1 to the S phase. This overexpression may be responsible for the refractoriness.

Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients.

Background: Reduced levels of membrane essential polyunsaturated fatty acids (EPUFAs) and increased levels of lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) have been observed in chronic medicated schizophrenics. The relationship of EPUFA and TBARS to psychopathology is unclear, since their levels may be altered differentially by duration of illness and antipsychotic treatment. To minimize these confounds, their levels were compared among never-medicated patients in early illness, medicated patients and control subjects with similar lifestyle and common ethnic background.

A new category of psychotropic drugs: neuroactive lipids as exemplified by ethyl eicosapentaenoate (E-E).

New treatments for psychiatric disorders are urgently required. Recent reviews show that there have been no improvements in efficacy of drugs for either affective disorders or schizophrenia since the first compounds were introduced over 40 years ago. Neuroactive lipids represent an entirely novel class of psychotropic compounds.

Phospholipid metabolism and depression: the possible roles of phospholipase A2 and coenzyme A-independent transacylase.

Phospholipids make up 60 per cent of the dry weight of the brain. They are essential for neuronal and especially for synaptic structure and play key roles in the signal transduction responses to dopamine, serotonin, glutamate and acetyl choline. The unsaturated fatty acid components of phospholipids are abnormal in depression, with deficits of eicosapentaenoic acid and other omega-3 fatty acids and excesses of the omega-6 fatty acid arachidonic acid.

A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.

Background: In depressed patients, low blood levels of eicosapentaenoic acid are seen. We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients.

Methods: We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a standard antidepressant.