BACKGROUND AND AIMS:The endocannabinoid (eCB) system includes ligands (anandamide and 2-arachidonoyl glycerol, 2-AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress-related model of visceral hypersensitivity induced by the selective corticotropin-releasing factor receptor subtype 1 (CRF1) agonist, cortagine. METHODS:Male Sprague-Dawley rats were injected subcutaneously (SC) with URB597 (3 mg/kg) or vehicle and 2 h later, intraperitoneally with cortagine (10 μg/kg) or vehicle. The visceromotor responses (VMR) were assessed to a first CRD (baseline) before injections, and to a second CRD 15 min after the last treatment. Brain, jejunum, and proximal colon were collected from treated and naïve rats for levels quantification of three fatty acid amides (FAAs) [anandamide (arachidonyl-ethanolamide, AEA), oleoyl-ethanolamide (OEA) and palmitoyl-ethanolamide (PEA)], and 2-AG. In separate animals, defecation/diarrhea were monitored after URB597 and cortagine. KEY RESULTS:URB597 inhibited cortagine-induced increased VMR at 40 mmHg (89.0 ± 14.8% vs. 132.5 ± 15.6% for vehicle SC, p < 0.05) and 60 mmHg (107.5 ± 16.1% vs. 176.9 ± 24.4% for vehicle SC, p < 0.001) while not influencing basal VMR. In URB597 plus cortagine group, FAAs levels increased in the brain and intestinal tissue while 2-AG did not change. URB597 did not modify cortagine-induced defecation/diarrhea versus vehicle. CONCLUSIONS AND INFERENCES:URB597 shows efficacy to elevate brain and intestinal FAAs and to counteract the colonic hypersensitivity induced by peripheral activation of CRF1 signaling supporting a potential strategy of FAAH inhibitors to alleviate stress-related visceral hypersensitivity.
BACKGROUND:School personnel are important for communicating with parents about school vaccination programs and recognizing influenza outbreaks. This study examined knowledge, attitudes, and practices of school personnel regarding seasonal and 2009 H1N1 influenza, vaccinations, and school outbreak investigations.METHODS:Data were analyzed from survey interviews of 58 elementary and middle school personnel in 2010.RESULTS:Principals, assistant principals, and nurses have higher knowledge than front office clerks regarding seasonal (odds ratio [OR]: 2.50, 95% confidence interval [CI]: 1.15-5.42) and 2009 H1N1 influenza (OR: 2.04, 95% CI: 1.19-3.71). During 2009-2010, 63.8 and 19.0% of school personnel received seasonal and 2009 H1N1 influenza vaccine, respectively. Personnel were more likely to be vaccinated against seasonal influenza if they believed the vaccine was safe (OR: 2.26, 95% CI: 1.21-4.19). Of those unvaccinated against 2009 H1N1, 48.9% also cited safety concerns. While every principal, assistant principal, and nurse received both infectious diseases and outbreak trainings, only 42.5 and 27.5% of clerks received these trainings, respectively (p < .001), and 30% of clerks believed outbreak recognition was not their responsibility.CONCLUSION:The level of knowledge regarding influenza illness, vaccination, and outbreaks among subjects was low overall. Education of school personnel may improve school vaccination programs and control of influenza outbreaks.
AGA Abstracts(group 3 and group 4) compared to group 1 and group 2 (p<0.01).Overall, the rats with neonatal acid exposure and rechallenged in adulthood (group 4) exhibited the highest expression of NR1 and PSD-95.CONCLUSIONS: Early life esophageal acid exposure accentuates the expression of NR1 and PSD-95 in ACC neurons in response to acid rechallenge in adulthood.This neuronal plasticity in the ACC circuitry may be responsible for enhanced nociceptive transmission in visceral hypersensitivity.