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Biomedical subjects

Iain Glen

Publications and source records attributed to Iain Glen.

8 recordsLinked to original sources
PubMed2007

Antioxidant modulation of oxidant-stimulated uptake and release of arachidonic acid in eicosapentaenoic acid-supplemented human lymphoma U937 cells.

Omega-3 polyunsaturated fatty acids (PUFA) are increasingly finding use as treatments for a variety of medical conditions. PUFA supplementation can, however, result in increased oxidative stress causing elevated turnover rate of membrane phospholipids, impairment of membrane integrity and increased formation of inflammatory mediators. The aim of this study was to determine which antioxidant compounds were most effective in ameliorating the stimulation of phospholipid turnover by oxidative stress. U937 cells were supplemented with eicosapentaenoic acid and either ascorbic acid, alpha-tocopherol, beta-carotene or astaxanthin prior to being challenged with oxidant. Although all antioxidants were found to be effective in decreasing oxidant-stimulated peroxide formation, only alpha-tocopherol significantly decreased oxidant-stimulated release of 3H-labeled arachidonic acid (AA), while ascorbic acid markedly increased release. All antioxidants except alpha-tocopherol decreased oxidant-stimulated 3H-AA uptake. Our data suggest that antioxidants are not equally effective in combating the effects of oxidative stress upon membrane phospholipid turnover, and that optimal protection will require mixtures of antioxidants.

Antioxidants↗
PubMed2005

Differential effects of eicosapentaenoic and docosahexaenoic acids upon oxidant-stimulated release and uptake of arachidonic acid in human lymphoma U937 cells.

The use of n-3 polyunsaturated fatty acids, as found in fish-oil derived dietary supplements, as anti-inflammatory agents is supported by a variety of biochemical and physiological data. Recent studies investigating the therapeutic potential of long chain (>C20) n-3 fatty acids in mental illness have lead to the conclusion, however, that not all n-3 fatty acid types are equally efficacious. In particular eicosapentaeoic acid (EPA) appears to possess antidepressant and antipsychotic activity, while docosahexaenoic acid (DHA) does not, an effect suggested to be due to a differential ability to antagonize arachidonic acid (AA)-dependent cell signalling. In this study, we examine the effect of EPA and DHA supplementation upon uptake and release of arachidonic acid stimulated by tert-butyl hydroperoxide/Fe2+ in U937 cells. Oxidant-stimulated 3H-AA release from cells was enhanced by pre-treatment with EPA, DHA and AA, but not stearic or oleic acids for 18 days, with the order of effect magnitude being EPA > DHA = AA. Supplementation of cells for 1 day gave qualitatively similar results, although the effect magnitude was smaller. To determine whether enhanced release was due to decreased reuptake of AA, cells were cultured in the presence of 10 microM fatty acids. Pre-treatment of cells with EPA, and to a lesser extent AA, but not DHA, inhibited uptake of 3H-AA measured subsequent to the removal of unesterified fatty acids. This study suggests that, in U937 cells, EPA can alter the rate of uptake and release of AA from phospholipids in an exposure time-dependent manner, whereas DHA has no or little effect. Our results predict that EPA will have a more pronounced effect upon AA-dependent processes compared to DHA, and suggests that the relative amounts of EPA and DHA in fish oil supplements may modify their biochemical, and potentially, behavioural effects.

Arachidonic Acid↗
PubMed2004

Delayed vasodilatory response to methylnicotinate in patients with unipolar depressive disorder.

BACKGROUND: Recent evidence has suggested an important role for lipids in the etiology and treatment of depression. Methylnicotinate-induced vasodilation can be used to investigate lipid-dependent signalling mechanisms involving the phospholipase A2 (PLA2)/cyclooxygenase pathway, an important signalling system involved in the action of several neurotransmitters including serotonin. To investigate whether abnormalities in this signalling system may occur in depressive illness, we undertook a study of methylnicotinate response in unipolar depression (UD). METHODS: Methylnicotinate was applied to the forearm of 20 patients with depression and 38 age and sex-matched healthy volunteers (HV). The resulting erythema was assessed over a 15-min period. RESULTS: Methylnicotinate-induced erythema was reduced in subjects with depression compared to HV at 5 min after application, it returned to normal after 15 min. Thus, although the maximal response to methylnicotinate appears normal, patients with UD exhibit an apparently delayed response. LIMITATIONS: The major limitation is that all unipolar patients were medicated at the time of testing. CONCLUSIONS: Our results support the hypothesis that UD may be associated with abnormalities in lipid-associated signalling systems, and may provide insight into how lipid intake may modulate depressive symptoms.

Adult↗
PubMed2003

On the relationship between methylnicotinate-induced skin flush and fatty acids levels in acute psychosis.

Vasodilation induced by methylnicotinate, a fatty acid- and cyclooxygenase-dependent process, is reduced or absent in patients with schizophrenia. This phenomenon has been suggested to be useful as a diagnostic test for the illness. To determine whether reduced flushing is specific to schizophrenia and is caused by a deficiency in membrane fatty acids, the extent of topically applied methylnicotinate-induced vasodilation was measured in 23 subjects with schizophrenia, 20 subjects with bipolar disorder and 34 healthy volunteers along with red cell fatty acid concentrations and measures of clinical severity. Although there was a significant decrease in an estimate of vasodilation (erythema) compared with healthy volunteers in both schizophrenia and bipolar groups, the schizophrenia group responded significantly less than subjects with bipolar disorder. The reduction in the bipolar group was partly due to a delayed vasodilatory reaction, an effect not observed in subjects with schizophrenia. In subjects with schizophrenia, there were no significant correlations between methylnicotinate response and fatty acid concentrations. The authors conclude that the methylnicotinate procedure can differentiate schizophrenia from other serious mental illness. The methylnicotinate insensitivity in schizophrenia, however, is likely to be due to a deficiency in the fatty acid precursors required for the vasodilatory reaction.

Administration, Topical↗
PubMed2003

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. Differences were detected between storage conditions. A second prospective study was conducted to investigate the effect of differential storage conditions on RBC membrane fatty acids from schizophrenic patients. We found that storage at -20 degrees C was associated with reduced levels of PUFAs. Comparison of decay rates suggest that schizophrenics decay approximately twice as rapidly as controls. Furthermore, this phenomenon appears to be specific for the longer chain PUFAs suggesting that an enzymatic process may be responsible, e.g. elevated phospholipase A(2) activity, as opposed to simple chemical oxidation.

Blood Preservation↗
PubMed2003

Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) comprises a range of behavioural problems including inattention, hyperactivity and impulsivity. Diagnosis and treatment of the disorder is made difficult due to its unknown biological basis. Several studies have identified abnormalities in membrane fatty acids in some subjects with ADHD, and some success has been reported using lipid therapies. We have measured exhalant ethane levels, a non-invasive measure of oxidative damage to n-3 fatty acids, to probe biochemical alterations in ADHD. Patients with ADHD (N = 10) had higher levels of ethane in exhalant than in healthy volunteers (N = 12) with approximately 50% of ADHD cases being above the control range. In contrast, levels of butane, a marker of protein oxidation, were unaltered. Our data, although preliminary, suggests that some patients with ADHD have higher rates of oxidative breakdown of n-3 polyunsaturated fatty acids (PUFAs). Such a biochemical abnormality may underlie the previously observed fatty acid deficiencies, as well as providing further rationale for the use of anti-oxidant and/or lipid supplementation therapy in the treatment of ADHD. Larger studies of ADHD using this non-invasive assessment of oxidative stress appear warranted.

Attention Deficit Disorder with Hyperactivity↗