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High levels of PGE(2) have been implicated in the pathogenesis of intestinal inflammatory disorders such as necrotizing enterocolitis (NEC) and peritonitis. However, PGE(2) has a paradoxical effect: its low levels promote intestinal homeostasis, whereas high levels may contribute to pathology. These concentration-dependent effects are mediated by four receptors, EP1-EP4. In this study, we evaluate the effect of blockade of the low affinity pro-inflammatory receptors EP1 and EP2 on expression of COX-2, the rate limiting enzyme in PGE(2) biosynthesis, and on gut barrier permeability using cultured enterocytes and three different models of intestinal injury. PGE(2) upregulated COX-2 in IEC-6 enterocytes, and this response was blocked by the EP2 antagonist PF-04418948, but not by the EP1 antagonist ONO-8711 or EP4 antagonist E7046. In the neonatal rat model of NEC, EP2 antagonist and low dose of COX-2 inhibitor Celecoxib, but not EP1 antagonist, reduced NEC pathology as well as COX-2 mRNA and protein expression. In the adult mouse endotoxemia and cecal ligation/puncture models, EP2, but not EP1 genetic deficiency decreased COX-2 expression in the intestine. Our results indicate that the EP2 receptor plays a critical role in the positive feedback regulation of intestinal COX-2 by its end-product PGE(2) during inflammation and may be a novel therapeutic target in the treatment of NEC.

The use of lactobacilli in prevention of necrotizing enterocolitis (NEC) is hampered by insufficient knowledge about optimal species/strains and effects on intestinal bacterial populations. We therefore sought to identify lactobacilli naturally occurring in postnatal rats and examine their ability to colonize the neonatal intestine and protect from NEC. L. murinus, L. acidophilus, and L. johnsonii were found in 42, 20, and 1 out of 51 4-day old rats, respectively. Higher proportion of L. murinus in microbiota correlated with lower NEC scores. Inoculation with each of the three species during first feeding significantly augmented intestinal populations of lactobacilli four days later, indicating successful colonization. L. murinus, but not L. acidophilus or L. johnsonii, significantly protected against NEC. Thus, lactobacilli protect rats from NEC in a species- or strain-specific manner. Our results may help rationalizing probiotic therapy in NEC.

Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in premature infants; yet its pathogenesis remains poorly understood. To evaluate the role of intestinal bacteria in protection against NEC, we assessed the ability of naturally occurring intestinal colonizer E. coli EC25 to influence composition of intestinal microbiota and NEC pathology in the neonatal rat model. Experimental NEC was induced in neonatal rats by formula feeding/hypoxia, and graded histologically. Bacterial populations were characterized by plating on blood agar, scoring colony classes, and identifying each class by sequencing 16S rDNA. Binding of bacteria to, and induction of apoptosis in IEC-6 enterocytes were examined by plating on blood agar and fluorescent staining for fragmented DNA. E. coli EC 25, which was originally isolated from healthy rats, efficiently colonized the intestine and protected from NEC following introduction to newborn rats with formula at 106 or 108 cfu. Protection did not depend significantly on EC25 inoculum size or load in the intestine, but positively correlated with the fraction of EC25 in the microbiome. Introduction of EC25 did not prevent colonization with other bacteria and did not significantly alter bacterial diversity. EC25 neither induced cultured enterocyte apoptosis, nor protected from apoptosis induced by an enteropathogenic strain of Cronobacter muytjensii. Our results show that E. coli EC25 is a commensal strain that efficiently colonizes the neonatal intestine and protects from NEC.

Enterococcus faecalis is a ubiquitous intestinal symbiont and common early colonizer of the neonatal gut. Although colonization with E. faecalis has been previously associated with decreased NEC pathology, these bacteria have been also implicated as opportunistic pathogens. Here we characterized 21 strains of E. faecalis, naturally occurring in 4-day-old rats, for potentially pathogenic properties and ability to colonize the neonatal gut. The strains differed in hemolysis, gelatin liquefaction, antibiotic resistance, biofilm formation, and ability to activate the pro-inflammatory transcription factor NF-κB in cultured enterocytes. Only 3 strains appreciably colonized the neonatal intestine on day 4 after artificial introduction with the first feeding. The best colonizer, strain BB70, effectively displaced maternal E. faecalis and significantly increased NEC pathology. Our results show that colonization with E. faecalis may predispose neonates to NEC.

Purpose – The purpose of this paper is to determine the awareness towards ethnic foods made with traditional spices among US and Thai consumers.Design/methodology/approach – Data on the awareness and use of ethnic cuisines and spices were collected from 100 consumers in a Midwestern university town in the USA and 100 consumers in Bangkok, Thailand. Consumers were also asked to identify ethnic spice blends by tasting spice blends in rice and they ranked the perceived health benefits of 15 ethnic cuisines.Findings – The results showed that more Thai consumers (94 percent) shop at ethnic grocery stores than US consumers (55 percent). Also, Thai consumers are more likely to consume ethnic foods from nearby countries, but US consumers have tried a greater variety of ethnic foods. Neither group generally was able to identify a cuisine based only on the spice flavors, although Thai consumers were slightly better at doing so. Asian cuisines were perceived to have the greatest health benefits to both American and ...

This article provides information on a decade of trends and prevalence of substance use at a Midwestern prohibitionist university. Trends were based on three data collection times, 1995, 2000, and 2005. This information was compared with results of a number of national surveys to identify trends in the data. Total averages for the prohibitionist sample were 42.6% for alcohol use; 18.2% for binge drinking; 35.4% for tobacco use; and 34.1% for marijuana use. With the exception of binge drinking, which remained stable, the gap between substance use rates for the prohibitionist university and the results of national surveys have widened slightly.

Necrotizing enterocolitis remains one of the most vexing problems in the neonatal intensive care unit. Risk factors for NEC2 include prematurity, formula feeding, and inappropriate microbial colonization of the GI tract. The pathogenesis of NEC is believed to involve weakening of the intestinal barrier by perinatal insults, translocation of luminal bacteria across the weakened barrier, an exuberant inflammatory response, and exacerbation of the barrier damage by inflammatory factors, leading to a vicious circle of inflammation-inflicted epithelial damage. Nitric oxide (NO), produced by inducible NO synthase (iNOS) and reactive NO oxidation intermediates play a prominent role in the intestinal barrier damage by inducing enterocyte apoptosis and inhibiting the epithelial restitution processes, namely enterocyte proliferation and migration. The factors that govern iNOS upregulation in the intestine are not well understood, which hampers efforts in developing NO/iNOS-targeted therapies. Similarly, efforts to identify bacteria or bacterial colonization patterns associated with NEC have met with limited success, because the same bacterial species can be found in NEC and in non-NEC subjects. However, microbiome studies have identified the three important characteristics of early bacterial populations of the GI tract: high diversity, low complexity, and fluidity. Whether NEC is caused by specific bacteria remains a matter of debate, but data from hospital outbreaks of NEC strongly argue in favor of the infectious nature of this disease. Studies in Cronobacter muytjensii have established that the ability to induce NEC is the property of specific strains rather than the species as a whole. Progress in our understanding of the roles of bacteria in NEC will require microbiological experiments and genome-wide analysis of virulence factors.

Development of necrotizing enterocolitis (NEC) requires a susceptible host, typically a premature infant or an infant with congenital heart disease, enteral feedings and bacterial colonization. Although there is little doubt that microbes are critically involved in the pathogenesis of NEC, the identity of specific causative pathogens remains elusive. Unlike established normal adult gut microbiota, which is quite complex, uniform, and stable, early postnatal bacterial populations are simple, diverse, and fluid. These properties complicate studies aimed at elucidating characteristics of the gut microbiome that may play a role in the pathogenesis of NEC. A broad variety of bacterial, viral, and fungal species have been implicated in both clinical and experimental NEC. Frequently, however, the same species have also been found in physiologically matched healthy individuals. Clustered outbreaks of NEC, in which the same strain of a suspected pathogen is detected in several patients suggest, but do not prove, a causative relationship between the specific pathogen and the disease. Studies in Cronobacter sakazakii, the best characterized NEC pathogen, have demonstrated that virulence is not a property of a bacterial species as a whole, but rather a characteristic of certain strains, which may explain why the same species can be pathogenic or non-pathogenic. The fact that a given microbe may be innocuous in a full-term, yet pathogenic in a pre-term infant has led to the idea of opportunistic pathogens in NEC. Progress in understanding the infectious nature of NEC may require identifying specific pathogenic strains and unambiguously establishing their virulence in animal models.

The in vivo role of endothelial nitric oxide synthase (eNOS) uncoupling mediating oxidative stress in ischemia/reperfusion (I/R) injury has not been well established. In vitro, eNOS coupling refers to the reduction of molecular oxygen to L-arginine oxidation and generation of L-citrulline and nitric oxide NO synthesis in the presence of an essential cofactor, tetrahydrobiopterin (BH(4)). Whereas uncoupled eNOS refers to that the electron transfer becomes uncoupled to L-arginine oxidation and superoxide is generated when the dihydrobiopterin (BH(2)) to BH(4) ratio is increased. Superoxide is subsequently converted to hydrogen peroxide (H(2)O(2)). We tested the hypothesis that promoting eNOS coupling or attenuating uncoupling after I/R would decrease H(2)O(2)/increase NO release in blood and restore postreperfused cardiac function. We combined BH(4) or BH(2) with eNOS activity enhancer, protein kinase C epsilon (PKC ε) activator, or eNOS activity reducer, PKC ε inhibitor, in isolated rat hearts (ex vivo) and femoral arteries/veins (in vivo) subjected to I(20 min)/R(45 min). When given during reperfusion, PKC ε activator combined with BH(4), not BH(2), significantly restored postreperfused cardiac function and decreased leukocyte infiltration (p 0.01) while increasing NO (p 0.05) and reducing H(2)O(2) (p 0.01) release in femoral I/R veins. These results provide indirect evidence suggesting that PKC ε activator combined with BH(4) enhances coupled eNOS activity, whereas it enhanced uncoupled eNOS activity when combined with BH(2). By contrast, the cardioprotective and anti-oxidative effects of the PKC ε inhibitor were unaffected by BH(4) or BH(2) suggesting that inhibition of eNOS uncoupling during reperfusion following sustained ischemia may be an important mechanism.

RESULTS: During the study period, 311 patients (79% M) underwent repair at a median age of 14 years (IQR 13-16). Median Haller index was 4 (IQR 3.5-4.9). Median duration of follow up was 3.8 years (range 0-16 years), reoperations were necessary in 26 (8%) patients and 23 (7%) patients experienced bar migration (of which 16 [5%] required reoperation, median time from repair of 26 days [IQR range 15-70]). Of the 101 (32%) patients who have had their bars removed electively, 10 (10%) required reoperation for recurrence (mean SD, 29 14 vs 46 25 months for non-recurrence, p1⁄40.036). Method of bar fixation was associated with reoperation: wire fixation (HR1⁄43.16, p1⁄40.014) and bar stabilizer (HR1⁄44.57, p1⁄40.002) use was associated with increased risk, while bilateral pericostal suture fixation with decreased risk (HR1⁄40.15, 95% CI: 0.06-0.40, p 50 cases1⁄4