Oxidation of oxa and thia fatty acids and related compounds catalysed by 5-and 15-lipoxygenase

The modified fatty acids, (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid, 3-[(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid, N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine and N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid, all react with soybean 15-lipoxygenase. The products were treated with triphenylphosphine to give alcohols, which were isolated using HPLC. Analysis of the alcohols using negative ion tandem electrospray mass spectrometry, and by comparison with compounds obtained by autoxidation of arachidonic acid, shows that each enzyme catalysed oxidation occurs at the omega -6 position of the substrate. In a similar fashion, it has been found that (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid and N-[(all-Z)-(eicosa-5,8, 11.14-tetraenylthio)]propionic acid each undergoes regioselective oxidation at the carboxyl end of the polyene moiety on treatment with potato 5-lipoxygenase. Neither (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid nor N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid reacts in the presence of this enzyme, while N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine affords the C11' oxidation product. The alcohol derived from (Z,Z,Z)-(octadeca-6,9, 12-trienyloxy)acetic acid using the 15-lipoxygenase reacts at the C6' position with the 5-lipoxygenase. (C) 2001 Elsevier Science Ltd. All rights reserved.

Promoting physical activity among middle-aged and older adults in health care settings

Physical inactivity continues to be a significant public health issue for middle-aged and older adults. This review focuses on physical activity interventions targeting older adults in health care settings. The literature in this area is limited and the results to date disappointing. Much remains to be done to develop effective interventions targeting older adults, especially those from underserved groups. Attention also needs to be paid to maintenance of initial treatment gains and to linking primary-care-based physical activity interventions to community-based resources. Recognition in the social and behavioral sciences of the importance of social-environmental influences on health and health behaviors mandates both a multidisciplinary and a multilevel intervention approach to the problem of physical inactivity.

Suicidal ideation and suicide attempts as predictors of mental health service use

Objective: To examine the extent to which suicidal ideation and suicide attempts are predictive of service use. Design and setting: The National Survey of Mental Health and Wellbeing considered service utilisation in relation to self-reported mental health problems. Service utilisation was inquired of in relation to hospital-based care (including both specialist mental health and general care settings), as well as consultations with a range of health professionals (both specialist and non-specialist mental health professionals, including psychiatrists, psychologists and general practitioners) on an outpatient basis. Participants: Secondary analysis of self-report data from 10 641 randomly selected Australian adults who participated in the National Survey of Mental Health and Wellbeing in 1997. The key predictor variables were reported suicidal ideation and suicide attempts over the past 12 months. Main outcome measures: Use of services for mental health problems (past 12 months). Results: When considered in isolation, individuals reporting suicidal ideation were more likely to make use of at least one type of service for mental health problems than non-suicidal individuals (OR, 17.3; 95% Cl, 13.2-22.6), and individuals reporting suicide attempts were even more likely to do so (OR, 32.3; 95% CI, 9.0-115.4). In the case of suicidal ideation, this effect remained significant after controlling for a range of potential confounders. For suicide attempts, the effect of mental health service use was no longer significant after other variables were taken into account. Conclusions: Suicidal individuals are likely to make use of services, and a high proportion of suicides may be preventable through appropriate healthcare system responses.

Methods for prediction of peptide binding to MHC molecules: A comparative study

Background: A variety of methods for prediction of peptide binding to major histocompatibility complex (MHC) have been proposed. These methods are based on binding motifs, binding matrices, hidden Markov models (HMM), or artificial neural networks (ANN). There has been little prior work on the comparative analysis of these methods. Materials and Methods: We performed a comparison of the performance of six methods applied to the prediction of two human MHC class I molecules, including binding matrices and motifs, ANNs, and HMMs. Results: The selection of the optimal prediction method depends on the amount of available data (the number of peptides of known binding affinity to the MHC molecule of interest), the biases in the data set and the intended purpose of the prediction (screening of a single protein versus mass screening). When little or no peptide data are available, binding motifs are the most useful alternative to random guessing or use of a complete overlapping set of peptides for selection of candidate binders. As the number of known peptide binders increases, binding matrices and HMM become more useful predictors. ANN and HMM are the predictive methods of choice for MHC alleles with more than 100 known binding peptides. Conclusion: The ability of bioinformatic methods to reliably predict MHC binding peptides, and thereby potential T-cell epitopes, has major implications for clinical immunology, particularly in the area of vaccine design.