Publications

AIMS

To test aripiprazole for efficacy in decreasing use in methamphetamine-dependent adults, compared to placebo.

DESIGN

Participants were randomized to receive 12 weeks of aripiprazole or placebo, with a 3-month follow-up and a platform of weekly 30-minute substance abuse counseling.

SETTING

The trial was conducted from January 2009 to March 2012 at the San Francisco Department of Public Health.

PARTICIPANTS

Ninety actively using, methamphetamine-dependent, sexually active adults were recruited from community venues.

MEASUREMENTS

The primary outcome was regression estimated reductions in weekly methamphetamine-positive urines. Secondary outcomes were study medication adherence [by self-report and medication event monitoring systems (MEMS)], sexual risk behavior and abstinence from methamphetamine.

FINDINGS

Participant mean age was 38.7 years, 87.8% were male, 50.0% white, 18.9% African American, and 16.7% Latino. Eighty-three per cent of follow-up visits and final visits were completed. By intent-to-treat, participants assigned to aripiprazole had similar reductions in methamphetamine-positive urines as participants assigned to placebo [risk ratio (RR) 0.88, 95% confidence interval (CI): 0.66-1.19, P = 0.41]. Urine positivity declined from 73% (33 of 45 participants) to 45% (18 of 40) in the placebo arm and from 77% (34 of 44) to 44% (20 of 35) in the aripiprazole arm. Adherence by MEMS and self-report was 42 and 74%, respectively, with no significant difference between arms (MEMS P = 0.31; self-report P = 0.17). Most sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug, although participants randomized to aripiprazole reported more akathisia, fatigue and drowsiness (P < 0.05).

CONCLUSION

Compared with placebo, aripiprazole did not reduce methamphetamine use significantly among actively using, dependent adults.

Mast cells are tissue-resident immune cells that play a central role in allergic disease. These contributions are largely dependent on the acquisition of antigen-specific immunoglobulin E (IgE). Despite this requirement, studies of mast cell and IgE interactions have overlooked the mechanism by which mast cells acquire IgE from the blood. To address this gap, we developed reporter IgE molecules and employed imaging techniques to study mast cell function in situ. Our data demonstrate that skin mast cells exhibit selective uptake of IgE based on perivascular positioning. Furthermore, perivascular mast cells acquire IgE by extending cell processes across the vessel wall to capture luminal IgE. These data demonstrate how tissue mast cells acquire IgE and reveal a strategy by which extravascular cells monitor blood contents to capture molecules central to cellular function.

The macrophage, a versatile cell type prominently involved in host defense and immunity, assumes a distinct state of alternative activation in the context of polarized type 2 immune responses such as allergic inflammation and helminth infection. This alternatively activated phenotype is induced by the canonical type 2 cytokines interleukin (IL)-4 and IL-13, which mediate expression of several characteristic markers along with a dramatic shift in macrophage metabolic pathways that influence surrounding cells and tissues. We discuss recent advances in the understanding of IL-4- and IL-13-mediated alternatively activated macrophages and type 2 immune responses; such advances have led to an expanded appreciation for functions of these cells beyond immunity, including maintenance of physiologic homeostasis and tissue repair.