‘Ecstasy’ and the use of sleep medications in a general community sample: a four-year follow-up

Aims: Animal models show that a single dose of MDMA (‘ecstasy’) can result in long-term disruption of sleep. We evaluated the relationship between ecstasy consumption and the use of sleep medications in humans after controlling for key factors. Design: The Personality and Total Health Through Life project uses a longitudinal cohort with follow-up every four years. This study reports data from waves two and three. Setting: Participants were recruited from the electoral roll in the Australian Capital Territory and Queanbeyan, New South Wales, Australia. Participants: Participants were aged 20-24 years at wave one (1999-2000). Measures: The study collected self-reported data on ecstasy, meth/amphetamine, cannabis, alcohol, tobacco and use of sleeping medications (pharmaceutical or other substances). Depression was categorised with the Brief Patient Health Questionnaire (BPHQ). Other psychosocial measures included lifetime traumas. We used generalised estimating equations to model outcomes. Results: Ecstasy data were available from 2128 people at wave two and 1977 at wave three: sleeping medication use was reported by 227 (10.7%) respondents at wave two and 239 (12.1%) at wave three. Increased odds ratios (OR) for sleeping medication use was found for those with depression (OR=1.88, (95% confidence interval (CI) 1.39, 2.53), women (OR=1.44, 95% CI 1.13, 1.84), and increased by 19% for each lifetime trauma. Ecstasy use was not a significant predictor, but >monthly versus never meth/amphetamine use increased the odds (OR=3.03, 95% CI 1.30, 7.03). Conclusion: The use of ecstasy was not associated with the use of sleeping medications controlling for other risk factors.The PATH study was supported by an NHMRC Program Grant 179805 and NHMRC Project Grant 157125. The sponsors had no role in the design, conduct or reporting of the research. None of the authors have connections (direct or indirect) with the tobacco, alcohol, pharmaceutical or gaming industries or any body substantially funded by one of these organisations

Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High-Risk Lesions.

ObjectiveTo evaluate whether biologic disease-modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression.MethodsIn this single-center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low-attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham-D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsAfter adjustment for the segment stenosis score, the Framingham-D'Agostino score, and time-varying Disease Activity Score in 28 joints using the C-reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long-term CVD risk (OR 0.15 [95% CI 0.04-0.60]). Noncalcified and low-attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low-attenuation plaque at baseline (OR 0.21 [95% CI 0.04-0.99] and OR 0.08 [95% CI 0.01-0.70], respectively), but not in those without noncalcified or low-attenuation plaque. Per-segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05-15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17-0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low-attenuation plaque loss (P = 0.042).ConclusionOur findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis

3-hydroxykynurenine suppresses CD4+ T-cell proliferation, induces T-regulatory-cell development, and prolongs corneal allograft survival

Copyright © 2011 Association for Research in Vision and Ophthalmology. This article is available open access through the publisher’s website at the link below.Purpose. IDO (indoleamine 2,3-dioxygenase) modulates the immune response by depletion of the essential amino acid tryptophan, and IDO overexpression has been shown to prolong corneal allograft survival. This study was conducted to examine the effect of kynurenines, the products of tryptophan breakdown and known to act directly on T lymphocytes, on corneal graft survival. Methods. The effects of kynurenines on T-cell proliferation and death, T-regulatory-cell development, and dendritic cell function, phenotype, and viability were analyzed in vitro. The effect of topical and systemic administration of 3-hydroxykynurenine (3HK) on orthotopic murine corneal allograft survival was examined. Results. T-lymphocyte proliferation was inhibited by two of the four different kynurenines: 3HK and 3-hydroxyanthranilic acid (3HAA). This effect was accompanied by significant T-cell death. Neither 3HK nor 3HAA altered dendritic cell function, nor did they induce apoptosis or pathogenicity to corneal endothelial cells. Administration of systemic and topical 3HK to mice receiving a fully mismatched corneal graft resulted in significant prolongation of graft survival (median survival of control grafts, 12 days; of treated, 19 and 15 days, respectively; P < 0.0003). While systemic administration of 3HK was associated with a significant depletion of CD4+ T, CD8+ T, and B lymphocytes in peripheral blood, no depletion was found after topical administration. Conclusions. The production of kynurenines, in particular 3HK and 3HAA, may be one mechanism (in addition to tryptophan depletion) by which IDO prolongs graft survival. These molecules have potential as specific agents for preventing allograft rejection in patients at high rejection risk.Fight for Sight and the Wellcome Trust

Oxetanes from the Ring Contraction of ?-Triflates of ?-Lactones: Oxetane Nucleosides and Oxetane Amino Acids

?-Triflates of ?-lactones with potassium carbonate in methanol give efficient contraction of the ring to oxetane-1-carboxylates in which the oxygen substituent at C(3) of the oxetane is predominantly trans to the carboxylate at C(2), regardless of the stereochemistry of the starting triflate. The limitations of the procedure are discussed and compared with analogous reactions for the preparation of THF carboxylates. The potential of the contraction in the preparation of oxetane nucleosides (such as oxetanocin) and oxetane sugar amino acids (analogues of oxetin) as peptidomimetics with predisposition to form secondary structural motifs is illustrated