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Background: The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions. The stability of the drug in aqueous solution is unclear while difficulties can be encountered when preparing methylnicotinate solutions for this purpose. To aid in the determination of how long solutions of the drug should be stored before discarding we have used a collection of aged batches of methylnicotinate to determine the stability of the drug in aqueous solution., Findings: The degradation of methylnicotinate was determined in batches which had been stored at 4 degrees C for between 5 and 1062 days prior to analysis by High Performance Liquid Chromatography. The major degradation product of methylnicotinate was nicotinic acid which formed at an approximate rate of 0.5% of the starting methylnicotinate concentration per annum. Furthermore, the ability of methylnicotinate solutions of different ages to induce vasodilatation was assessed in healthy volunteers. No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days., Conclusion: Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.

Background: Selected ion flow tube mass spectrometry (SIFT-MS) allows the real time quantification of trace gases in air. Due to its tolerance of high humidity levels the technique is particularly suited to the chemical analysis of breath. The detection limit of SIFT-MS has previously reported to be approximately 5 - 10 PPBV which is insufficient for the measurement of some low abundance constituents of breath. Recent developments in the design of SIFT-MS instruments have increased the ion precursor count rates. It is, however, unclear as to how these advances will affect instrument sensitivity for breath analysis., Findings: Standard gases were prepared by adding known quantities of compounds present at zero or very low levels in breath (xylene and toluene) to either humidified bottled air or actual human breath. These were then analysed by SIFT-MS to calculate the limits of detection for each compound under conditions which mimic a single breath exhalation. For xylene and toluene the limits of detection was approximately 0.5 PPBV per 10 seconds of analysis time. Results gained using this level of sensitivity suggested the presence of low levels of the compounds indole and methylindole in human alveolar and static oral air, although further studies are necessary to confirm these findings., Conclusion: Recent advances in SIFT-MS have increased the techniques sensitivity for breath analysis into the sub PPBV range enabling the real time quantification of low level trace gases in human breath.

Background: This study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder., Methods: Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 x 70 x 70 mm3 voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra., Results: The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (rs = 0.714, p < 0.05)., Conclusion: Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

Background: Cigarette smoking is believed to cause oxidative stress by several mechanisms, including direct damage by radical species and the inflammatory response induced by smoking, and would therefore be expected to cause increased lipid peroxidation. The aim was to carry out the first study of the relationship of smoking in humans to the level of n-3 lipid peroxidation indexed by the level of ethane in exhaled breath., Methods: Samples of alveolar air were obtained from 11 smokers and 18 non-smokers. The air samples were analyzed for ethane using mass spectrometry., Results: The two groups of subjects were matched with respect to age and gender. The mean cumulative smoking status of the smokers was 11.8 (standard error 2.5) pack-years. The mean level of ethane in the alveolar breath of the group of smokers (2.53 (0.55) ppb) was not significantly different from that of the group of non-smokers (2.59 (0.29) ppb; p = 0.92). With all 29 subjects included, the Spearman rank correlation coefficient between ethane levels and cumulative smoking status was -0.11 (p = 0.58), while an analysis including only the smokers yielded a corresponding correlation coefficient of 0.11 (p = 0.75)., Conclusion: Our results show no evidence that cigarette smoking is related to increased n-3 lipid peroxidation as measured by expired ethane.

Background: A growing number of observational and epidemiological studies have suggested that mental illness, in particular mood disorders, is associated with reduced dietary intake and/or cellular abundance of omega-3 polyunsaturated fatty acids (PUFA). This has prompted researchers to test the efficacy of omega-3 PUFA in a range of different psychiatric disorders. We have critically reviewed the double blind placebo controlled clinical trials published prior to April 2007 to determine whether omega-3 PUFA are likely to be efficacious in these disorders., Results: Most trials involved a small number of participants but were largely well designed. Omega-3 PUFA were well tolerated by both children and adults with mild gastrointestinal effects being the only consistently reported adverse event. For schizophrenia and borderline personality disorder we found little evidence of a robust clinically relevant effect. In the case of attention deficit hyperactivity disorder and related disorders, most trials showed at most small benefits over placebo. A limited meta-analysis of these trials suggested that benefits of omega-3 PUFA supplementation may be greater in a classroom setting than at home. Some evidence indicates that omega-3 PUFA may reduce symptoms of anxiety although the data is preliminary and inconclusive. The most convincing evidence for beneficial effects of omega-3 PUFA is to be found in mood disorders. A meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression. Furthermore, meta-regression analysis suggests that supplementation with eicosapentaenoic acid may be more beneficial in mood disorders than with docosahexaenoic acid, although several confounding factors prevented a definitive conclusion being made regarding which species of omega-3 PUFA is most beneficial. The mechanisms underlying the apparent efficacy of omega-3 PUFA in mood disorders compared to schizophrenia are discussed as is a rational for the possibly greater efficacy of EPA compared to DHA., Conclusion: While it is not currently possible to recommend omega-3 PUFA as either a mono- or adjunctive-therapy in any mental illness, the available evidence is strong enough to justify continued study, especially with regard to attentional, anxiety and mood disorders.