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bEnterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in piglets; ETEC cells colonize the intestinal mucosa with adhesins and deliver toxins that cause fluid loss. This study determined the antiadhesive properties of bacterial exopolysaccharides (reuteran and levan) and related glycans (dextran and inulin) in a small intestinal segment perfusion (SISP) model. The SISP model used 10 jejunal segments from 5-week-old piglets. Five segments were infected with ETEC expressing K88 fimbriae (ETEC K88), while five segments were treated with saline. Every two segments (ETEC and non-ETEC infected) were infused with 65 ml of 10 g liter ؊1 of glycans or saline (control) for 8 h. High-resolution melting-curve (HRM) quantitative PCR (qPCR) indicated that E. coli is the dominant bacterium in infected segments, while other bacteria were predominant in noninfected segments. Infection by ETEC K88 was also verified by qPCR; gene copy numbers of K88 fimbriae and the heat-labile toxin (LT) in mucosal scrapings and outflow fluid of infected segments were significantly higher than those in noninfected segments. Genes coding for K88 fimbriae and LT were also detected in noninfected segments. LT amplicons from infected and noninfected segments were 99% identical over 481 bp, demonstrating the presence of autochthonous ETEC K88. All glycans reduced fluid loss caused by ETEC K88 infection. Reuteran tended (P ‫؍‬ 0.06) to decrease ETEC K88 levels in mucosal scraping sample, as judged by qPCR. Fluorescent in situ hybridization analysis demonstrated that reuteran significantly (P ‫؍‬ 0.012) decreased levels of adherent ETEC K88. Overall, reuteran may prevent piglet diarrhea by reducing adhesion of ETEC K88.

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Red blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China. Methods: A total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms. Results: Participants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013-6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms. Conclusion: Higher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.

ABSTRACT:Amiodarone is recognized as an effective drug in the treatment of arrhythmias. Previous experiments demonstrated that mono-Ndesethylamiodarone (MDEA) was the major circulating metabolite in humans. In addition, dealkylation, hydroxylation, and deamination were minor metabolic pathways. The purpose of this study was to identify the metabolites of amiodarone in the bile obtained from patients with T-tube drainage after oral drug administration. Amiodarone metabolism in vitro was also investigated using human liver microsomes (HLMs) and S9 fraction. Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) revealed 33 metabolites in human bile, including 22 phase I and 11 phase II metabolites. The major metabolites were MDEA (M7) and -carboxylate amiodarone (M12). Metabolite M12 was isolated from human bile, and the chemical structure was confirmed using UPLC-Q/TOF MS and 1 H NMR.Moreover, the authentic standards of two hydroxylated metabolites, 2-hydroxylamiodarone and 3-hydroxylamiodarone, were obtained through microbial transformation. Several novel metabolic pathways of amiodarone in human were proposed, including -carboxylation, deiodination, and glucuronidation. The in vitro study demonstrated that incubation of HLMs with amiodarone did not give rise to any carboxyl metabolites. In contrast, M12 and its metabolites were detected in human liver S9 incubation samples, and the production of these metabolites were inhibited almost completely by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, suggesting the involvement of alcohol dehydrogenase in the -carboxylation of amiodarone. Overall, UPLC-Q/TOF MS analysis leads to the discovery of several novel amiodarone metabolites in human bile and underscores the importance of bile as an excretion pathway.

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BMVD was associated with deeper MI, positive LVSI, positive LNM, and poor OS in patients with endometrial cancer. Therefore, angiogenesis is a useful measure for poor clinicopathological outcomes and prognosis in patients with endometrial cancer.

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