The effects of adrenal corticosteroids on subsequent adrenocorticotropin secretion are complex. Acutely (within hours), glucocorticoids (GCs) directly inhibit further activity in the hypothalamopituitary-adrenal axis, but the chronic actions (across days) of these steroids on brain are directly excitatory. Chronically high concentrations of GCs act in three ways that are functionally congruent. (i) GCs increase the expression of corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala, a critical node in the emotional brain. CRF enables recruitment of a chronic stress-response network. (ii) GCs increase the salience of pleasurable or compulsive activities (ingesting sucrose, fat, and drugs, or wheel-running). This motivates ingestion of ''comfort food.'' (iii) GCs act systemically to increase abdominal fat depots. This allows an increased signal of abdominal energy stores to inhibit catecholamines in the brainstem and CRF expression in hypothalamic neurons regulating adrenocorticotropin. Chronic stress, together with high GC concentrations, usually decreases body weight gain in rats; by contrast, in stressed or depressed humans chronic stress induces either increased comfort food intake and body weight gain or decreased intake and body weight loss. Comfort food ingestion that produces abdominal obesity, decreases CRF mRNA in the hypothalamus of rats. Depressed people who overeat have decreased cerebrospinal CRF, catecholamine concentrations, and hypothalamo-pituitary-adrenal activity. We propose that people eat comfort food in an attempt to reduce the activity in the chronic stress-response network with its attendant anxiety. These mechanisms, determined in rats, may explain some of the epidemic of obesity occurring in our society.corticotropin-releasing factor ͉ glucocorticoids ͉ high fat ͉ sucrose ͉ motivation O ur understanding of regulation of function in the hypothalamo-pituitary-adrenal (HPA) axis has changed profoundly in the last decades. The discovery of functions of the distributed cell groups of corticotropin-releasing factor (CRF) neurons, the motor neurons for activation of the pituitary and adrenal, as well as the tight interrelationships between calories, body weight, energy stores, and the HPA axis have occasioned revisions in our thinking. The upshot is a new working model, the output of which is modifiable through manipulation of caloric input (Fig. 1). The long-term consequences of such output modification in chronically stressed individuals may include deleterious weight gain, abdominal obesity, type II diabetes, increased cardiovascular morbidity, and mortality. We arrived at this model through interpretation of the results from studies on manipulation of energy balance, central CRF, and the effects of acute and chronic stress and glucocorticoid (GC) treatment in intact and adrenalectomized rats. GC Effects on HPA Function: Acute and ChronicCanonical GC-feedback inhibition of subsequent adrenocorticotropin (ACTH) secretion is easily demonstrated acutely, within the fi...

SUMMARY Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor (TLR) 5 exhibit a profound loss of flagellin-specific immunoglobulins (Ig) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5−/− gut. A diversity of microbiome members over-expressed flagellar genes in the TLR5−/− host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and down-regulated flagellar gene expression. Thus, innate-immunity directed development of flagellin-specific adaptive immune responses can modulate the microbiome’s production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.

Objective-Recent reports have linked oral health and periodontal disease indicators with increased risk of squamous cell carcinoma of head and neck (SCCHN). Thus far, evidence has been inconclusive; our objective was to study the association between oral health and SCCHN risk in the context of a large population-based study. Methods NIH Public Access Author ManuscriptCancer Causes Control. Author manuscript; available in PMC 2011 April 1. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript assessed using interview data on tooth loss and mobility, mouthwash use, and frequency of dental visits.Results-Subjects were 26-80 years old (median age = 61). The distribution of tooth loss among controls was 0-5 teeth = 60%; 5-14 = 15%; and 16-28 = 25%. After controlling for covariates, tooth loss did not yield any notable association with SCCHN (16-28 vs. 0-5 lost teeth: OR: 1.21, 95% CI: 0.94, 1.56). Self-reported history of tooth mobility was moderately associated with increased SCCHN risk (OR: 1.33, 95% CI: 1.07, 1.65); however, the association did not persist among never smokers. Routine dental visits were associated with 30% risk reduction (OR: 0.68, 95% CI: 0.53, 0.87).Conclusions-These data provide support for a possible modest association of periodontal disease, as measured by self-reported tooth loss indicators, but not tooth loss per se, with SCCHN risk.

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Our results highlight important racial differences in ET-adherence behaviors, perceptions of benefits/harms, and shared decision making that may be targeted with culturally tailored interventions.