Elevated salivary uric acid levels among adolescents with eating disorders.

OBJECTIVE: Uric acid (UA) is increasingly recognized as having important physiological roles and associated with several peripheral and central pathophysiological outcomes, and might play a role in eating disorders (ED) pathogenesis. We investigated whether UA levels are altered among adolescents with ED. METHODS: Morning salivary UA concentrations were compared between adolescents referred to treatment at the Herman Dana Center receiving a DSM-V diagnosis of an ED and matched healthy controls. RESULTS: Salivary UA was significantly elevated among ED compared with control values (ED mean 3.9 ± 1.2 mg/dl, control mean 2.9 ± 1.9 mg/dl, t = - 3.13 df = 81, p = 0.003). DISCUSSION: Salivary UA is elevated among adolescents with ED. Further studies are required to replicate and extend this finding and evaluate its generalizability as a state or trait marker as regards ED subtypes, other body fluids (plasma and cerebrospinal fluid), and recovery or premorbid stages, as well as its putative mechanistic relevance to ED. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: a potential link to stress resilience.

Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH). This study examines the effects of unpredictable, inescapable tail-shock stress (TSS) on alpha(2)-adrenoceptor (α(2A)-AR) and corticotropin-releasing factor 1 receptor (CRF(1)-R) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (COR) and striatum (STR). In NH rats, α(2A)-AR and CRF(1)-R were significantly down-regulated in LC after TSS. No changes in these receptor levels were observed in the LC of LH rats. GRK3, which phosphorylates receptors and thereby contributes to α(2A)-AR and CRF(1)-R down-regulation, was reduced in the LC of LH but not NH rats. GRK2 levels were unchanged. In AMG, GRK3 but not GRK2 levels were reduced in LH but not NH rats, and receptor regulation was impaired in LH rats. In STR, no changes in GRK3 or GRK2 levels were observed. Finally, protein carbonylation, an index of oxidative stress, was increased in the LC and AMG of LH but not NH rats. We suggest that reduced stress resilience after TSS may be related to oxidative stress, depletion of GRK3 and impaired regulation of α(2A)-AR and CRF(1)-R in LC.

Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of beta-adrenergic bronchodilators and corticosteroids.

BACKGROUND: Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR. OBJECTIVE: To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of beta-agonists. METHODS: The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol. RESULTS: IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 11.08; P = .26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice. CONCLUSIONS: The protective effects of fluticasone, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.