Bifidobacterium longum subsp. infantis in experimental necrotizing enterocolitis: alterations in inflammation, innate immune response, and the microbiota.

BackgroundProbiotics decrease the risk of necrotizing enterocolitis (NEC). We sought to determine the impact of Bifidobacterium longum subsp. infantis (B. infantis) in the established rat model of NEC.MethodsRat pups delivered 1 d prior to term gestation were assigned to one of three groups: dam fed (DF), formula fed (FF), or fed with formula supplemented with 5 × 10(6) CFU B. infantis per day (FF+Binf). Experimental pups were exposed to hypoxia and cold stress. Ileal tissue was examined for pathology and expression of inflammatory mediators, antimicrobial peptides, and goblet-cell products. Ceca were assessed for bacterial composition by analysis of the 16S rRNA sequence.ResultsAdministration of B. infantis significantly reduced the incidence of NEC, decreased expression of Il6, Cxcl1, Tnfa, Il23, and iNOS, and decreased expression of the antimicrobial peptides Reg3b and Reg3g. There was significant microbial heterogeneity both within groups and between experiments. The cecal microbiota was not significantly different between the FF and FF+Binf groups. Bifidobacteria were not detected in the cecum in significant numbers.ConclusionIn the rat model, the inflammation associated with NEC was attenuated by administration of probiotic B. infantis. Dysbiosis was highly variable, precluding determination of the precise role of the microbiota in experimental NEC

Preoperative neoadjuvant chemoradiation for locally advanced gastric adenocarcinoma

Aims and BackgroundTo evaluate toxicity and the radical resection rate in gastric adenocarcinoma treated with preoperative neoadjuvant chemoradiation.Materials & Methods32 patients, 22 males and 10 females with gastric adenocarcinoma, were treated with chemoradiation and hyperthermia.ResultsThe neoadjuvant regimen was completed as planned in 19/32 (59 %) patients; in the remaining patients the intensity of chemotherapy had to be reduced because of haematological and gastrointestinal toxicity. Surgical stage was as follows: 2 patients pathologically complete response, 3 patients AJCC stage I.A, 5 patients stage I.B, 7 patients stage II, 7 patients stage III.A, 1 patient stage III.B, 7 patients stage IV. R0 resection was achieved in 19/32 (59%) patients, R1 in 2/32 (6%) patients and R2 in 11 (34%) patients. Downstaging after neoadjuvant chemoradiotherapy was achieved in 17/32 (53%) patients. At the date of evaluation (31 March 2009), 4 patients were still alive 58, 81, 86 and 98 months from the date of diagnosis. Median survival was 18 months (95% confidence interval: 13–38 months). One-year survival was 69% (95% confidence interval: 53%–85%). Four-year survival was 19% (95% C.I.: 5%–34%).ConclusionsPreoperative neoadjuvant chemoradiotherapy has acceptable toxicity, and can lead to a high rate of R0 resections

Branched Chain Fatty Acids Reduce the Incidence of Necrotizing Enterocolitis and Alter Gastrointestinal Microbial Ecology in a Neonatal Rat Model

Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model.Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed); Control, hand-fed rat milk substitute; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed.NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed.At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects

Geologicka minulost zeme. Uvod do historicke geologie a paleontologie. Druhe, prepracovam vydani.

OPLADEN-RUG0