In vitro and in vivo evidence for anti-inflammatory properties of 2-methoxyestradiol.

2-Methoxyestradiol (2MEO) is an endogenous metabolite of 17ß-estradiol that interacts with estrogen receptors and microtubules. It has acute anti-inflammatory activity in animal models that is not attributable to known antiproliferative or antiangiogenic actions. Because macrophages are central to the innate inflammatory response, we examined whether suppression of macrophage activation by 2MEO could account for some of its anti-inflammatory effects. Inflammatory mediator production stimulated by lipopolysaccharide (LPS) and interferon-γ in the J774 murine macrophage cell line or human monocytes was measured after treatment with 2MEO or the anti-inflammatory agent dexamethasone. The effect of these agents on LPS-induced acute lung inflammation in mice was also examined. 2MEO suppressed J774 macrophage interleukin-6 and prostaglandin E2 production (by 30 and 47%, respectively, at 10 µM) and human monocyte tumor necrosis factor-α production (by 60% at 3 µM). Estradiol had no effect on J774 macrophage activation, nor did the estrogen receptor antagonist 7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17ß-diol (ICI 182,780) prevent the effects of 2MEO. The actions of 2MEO were not mimicked by the microtubule-interfering agents colchicine or paclitaxel. In mice exposed to LPS, bronchoalveolar lavage protein content, a measure of vascular leak and epithelial injury, was reduced to a comparable extent (~54%) by treatment with 2MEO (150 mg · kg⁻¹) or dexamethasone (1 mg · kg⁻¹). In addition, 2MEO reduced LPS-induced interleukin-6 gene expression. Thus, 2MEO modulates macrophage activation in vitro and has high-dose acute anti-inflammatory activity in vivo. These findings are consistent with the acute anti-inflammatory actions of 2MEO being mediated in part by the suppression of macrophage activation.

The role of sociology in the study of mental health ... and the role of mental health in the study of sociology.

This essay considers the dual roles occupied by the sociologist of mental health. These roles involve the articulation of social causation in the study of mental health outside of the discipline, coupled with the articulation within the discipline of the importance of mental health in the study of sociology. I consider these roles both through examples and speculation, emphasizing the unique combination of conceptual and methodological tools that define the intellectual terrain of this area of sociology. The advantage of this dual role--of looking outward while also looking inward--is that we are able to draw from the essential developments and innovations from one source and "move" these insights toward the other. The difficulties of this position are also clear: As an area, we may be structurally marginal from both perspectives, at the same time that we offer considerable analytic power that could significantly impact the direction of research involving mental health in both realms.

Measuring psychological well-being in the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging (CHSA) provided an opportunity to examine the positive aspects of aging. CHSA-2 included the 18-item Ryff multidimensional measure of well-being, which taps six core theoretical dimensions of positive psychological functioning. The measure was administered to 4,960 seniors without severe cognitive impairment or dementia at CSHA-2. Intercorrelations across scales were generally low. At the same time, the internal consistency reliability of each of the 6 subscales was not found to be high. Confirmatory factor analyses provide support for a 6-factor model, although some items demonstrate poor factor loadings. The well-being measures in CSHA-2 provide an opportunity to examine broad, descriptive patterns of well-being in Canadian seniors.