Dopamine Transporter Genotype as a Risk Factor for Obesity in African-American Smokers

Objective: To assess the association between a polymorphism related to dopamine function, dopamine transport (SLC6A3), and obesity in smokers. Research Methods and Procedures: Logistic regression was used to assess the relationship between this genetic polymorphism and obesity (body mass index ≥ 30 kg/m²) from a sample of 510 smokers who smoked at least 10 cigarettes per day and who were participating in a study designed to examine genetic and nongenetic predictors of response to a pharmacological treatment. Results: The likelihood of obesity in African Americans (N = 90) with the 10/10 SLC6A3 genotype was 5.16 times that of African Americans with 9/9 or 9/10 SLC6A3 genotypes (odds ratio = 5.16, confidence interval = 1.60 to 16.65). There was no association of the SLC6A3 genotype with obesity for non-Hispanic whites (N = 420). Discussion: These results suggest that variants of the dopamine transporter gene may be related to obesity in African-American smokers. Possible mechanisms responsible for the association between dopamine transport and obesity in African-American smokers are discussed.     

Systematic evaluation of the adrenocortical function in patients with paracoccidioidomycosis

Limited cortisol response to ACTH stimulation has been documented in 22 to 48% of patients with paracoccidioidomycosis (PM). Different approaches to interpret the test and inadequate selection of patients preclude an accurate appraisal of the actual incidence of adrenal insufficiency in PM. Rapid cosyntropin (ACTH) stimulation tests were performed in 38 consecutive patients (9 with the localized and 29 with the disseminated form of PM) and 40 normal controls. Subnormal cortisol responses to ACTH (60 minutes post-ACTH values below 455 nmol/l, 95% confidence limits) were found in only 4 patients (14%) with disseminated PM. If a retrospective sample of 6 patients studied previously (in whom tests were indicated due to clinical suspicion of Addison's disease) were included, or if the absolute cortisol increment above baseline was used for interpretation, we would find figures closer to those previously reported (23 and 24%, respectively). These data reflect that non-systematic evaluation or selection of a substandard criterion to interpret the test overestimates the frequency of adrenocortical insufficiency in PM.     

Assessing possible hybridization among managed Nubian ibex in North America

Hybridization among closely related species is a concern in zoo and aquarium populations where unpedigreed animals are frequently exchanged with the private sector. In this study, we examine possible hybridization in a group of Nubian ibex (Capra nubiana) imported into the Association of Zoos and Aquariums’ (AZA) Species Survival Program (SSP) from a private institution. These individuals appeared smaller in stature than adult SSP Nubian ibex and were excluded from breeding recommendations over the concern that they were hybrids. Twenty-six microsatellites were used to rule out recent hybridization with domestic goats, Siberian ibex (Capra sibirica), and Alpine ibex (Capra ibex). We argue that natural phenotypic variation across the large geographic range of Nubian ibex may account for the small stature of the imported ibex, as private institutions may have historically acquired individuals from locations that differed from the SSP founders. However, the imported Nubian ibex appeared genetically differentiated from the SSP Nubian ibex and may represent a source of genetic variation for the managed population.     

Maresin 1 attenuates pro-inflammatory activation induced by β-amyloid and stimulates its uptake

Alzheimer's disease (AD) is the most common dementia, characterized by pathological accumulation of β-amyloid (Aβ) and hyperphosphorylation of tau protein, together with a damaging chronic inflammation. The lack of effective treatments urgently warrants new therapeutic strategies. Resolution of inflammation, associated with beneficial and regenerative activities, is mediated by specialized pro-resolving lipid mediators (SPMs) including maresin 1 (MaR1). Decreased levels of MaR1 have been observed in AD brains. However, the pro-resolving role of MaR1 in AD has not been fully investigated. In the present study, human monocyte-derived microglia (MdM) and a differentiated human monocyte cell line (THP-1 cells) exposed to Aβ were used as models of AD neuroinflammation. We have studied the potential of MaR1 to inhibit pro-inflammatory activation of Aβ and assessed its ability to stimulate phagocytosis of Aβ₄₂. MaR1 inhibited the Aβ₄₂-induced increase in cytokine secretion and stimulated the uptake of Aβ₄₂ in both MdM and differentiated THP-1 cells. MaR1 was also found to decrease chemokine secretion and reduce the associated increase in the activation marker CD40. Activation of kinases involved in transduction of inflammation was not affected by MaR1, but the activity of nuclear factor (NF)-κB was decreased. Our data show that MaR1 exerts effects that indicate a pro-resolving role in the context of AD and thus presents itself as a potential therapeutic target for AD.