Aspirin : a review of its neurobiological properties and therapeutic potential for mental illness

There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor- and interleukin (IL)--6 , but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery.

Young women with type 1 diabetes' management of turning points and transitions

The authors used grounded theory to explore and develop a substantive theory to explain how 20 young women with type 1 diabetes managed their lives when facing turning points and undergoing transitions. The women experienced a basic social problem: being in the grip of blood glucose levels (BGLs), which consisted of three categories: (a) the impact of being susceptible to fluctuating BGLs, (b) the responses of other people to the individual woman’s diabetes, and (c) the impact of the individual women’s diabetes on other people’s lives. The women used a basic social process to overcome the basic social problem by creating stability, which involved using three interconnected subprocesses: forming meaningful
relationships, enhancing attentiveness to blood glucose levels, and putting things in perspective. Insights into the processes and strategies used by the women have important implications for provision of care and service delivery.

The mother-daughter guilt dynamic : effects of type 1 diabetes during life transitions

Aim. The aim of the study was to explore and describe the strategies young women with type 1 diabetes used to manage life transitions. The paper describes one aspect of how guilt dynamic often operates between mothers and daughters and how the women managed the guilt dynamic to create stability in their lives.
Background. When a child is diagnosed with diabetes, major transitional changes occur in the relationships between the mother and her child. The changes affect the psychological and social aspects of their lives and have a major impact on how young women manage their diabetes. A guilt dynamic between mothers and young women with diabetes emerged as a major theme in a larger study that investigated how young women with diabetes managed life transitions. Although the literature indicates that mothers of chronically ill children experience guilt feelings towards their children, little research was identified that addressed the emotional dynamics between mothers and daughters with diabetes.
Design. Using grounded theory method, interviews were conducted with 20 women with type 1 diabetes and five mothers during 2002 and 2003. Constant comparative analysis was used to analyse the data and develop an in-depth understanding of the experience of living with diabetes during life transitions.
Findings. The findings revealed that guilt feelings created a two-way dependency between mothers and their daughters with diabetes. The two-way dependency involved feelings of being a burden to each other, difficulty balancing responsibilities for diabetes management, difficulty relinquishing emotional and social dependency especially during life transitions. In addition, these issues were rarely discussed openly with each other or with health professionals. The findings provide additional information about the human experience of the mother–daughter relationship and the effect on coping with diabetes in the context of life transitions.
Conclusions. Understanding the impact diabetes has on the emotional and social well being of both women with type 1 diabetes and their mothers is critical in planning appropriate support for both groups. Most importantly, it is critical to understand the guilt dynamic that operates during young women with diabetes' life transitions when the daughters' dependency on their mother's control and responsibility for diabetes management undergo changes resulting in emotional responses, especially guilt feelings.
Relevance to clinical practice. Health professionals need to understand the emotional and social impact of the guilt dynamics between young women with type 1 diabetes and their mothers. Adequate and appropriate support can minimize the guilt feelings and enhance stability and quality of life for both mothers and their daughters, especially during major life transitions, such as motherhood.