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71.
Yohe HC O'Hara KA Hunt JA Kitzmiller TJ Wood SG Bement JL Bement WJ Szakacs JG Wrighton SA Jacobs JM Kostrubsky V Sinclair PR Sinclair JF 《American journal of physiology. Gastrointestinal and liver physiology》2006,290(6):G1269-G1279
The objective of this study was to determine whether Toll-like receptor 4 (TLR4) has a role in alcohol-mediated acetaminophen (APAP) hepatotoxicity. TLR4 is involved in the inflammatory response to endotoxin. Others have found that ethanol-mediated liver disease is decreased in C3H/HeJ mice, which have a mutated TLR4 resulting in a decreased response to endotoxin compared with endotoxin-responsive mice. In the present study, short-term (1 wk) pretreatment with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, caused no histologically observed liver damage in either C3H/HeJ mice or endotoxin-responsive C3H/HeN mice, despite an increase in nitrotyrosine levels in the livers of C3H/HeN mice. In C3H/HeN mice pretreated with the alcohols, subsequent exposure to APAP caused a transient decrease in liver nitrotyrosine formation, possibly due to competitive interaction of peroxynitrite with APAP producing 3-nitroacetaminophen. Treatment with APAP alone resulted in steatosis in addition to congestion and necrosis in both C3H/HeN and C3H/HeJ mice, but the effects were more severe in endotoxin-responsive C3H/HeN mice. In alcohol-pretreated endotoxin-responsive C3H/HeN mice, subsequent exposure to APAP resulted in further increases in liver damage, including severe steatosis, associated with elevated plasma levels of TNF-alpha. In contrast, alcohol pretreatment of C3H/HeJ mice caused little to no increase in APAP hepatotoxicity and no increase in plasma TNF-alpha. Portal blood endotoxin levels were very low and were not detectably elevated by any of the treatments. In conclusion, this study implicates a role of TLR4 in APAP-mediated hepatotoxicity. 相似文献
72.
Fournier D Hawari J Streger SH McClay K Hatzinger PB 《Applied and environmental microbiology》2006,72(10):6693-6698
N-Nitrosodimethylamine (NDMA) is a potent carcinogen and an emerging contaminant in groundwater and drinking water. The metabolism of NDMA in mammalian cells has been widely studied, but little information is available concerning the microbial transformation of this compound. The objective of this study was to elucidate the pathway(s) of NDMA biotransformation by Pseudomonas mendocina KR1, a strain that possesses toluene-4-monooxygenase (T4MO). P. mendocina KR1 was observed to initially oxidize NDMA to N-nitrodimethylamine (NTDMA), a novel metabolite. The use of 18O2 and H(2)18O revealed that the oxygen added to NDMA to produce NTDMA was derived from atmospheric O2. Experiments performed with a pseudomonad expressing cloned T4MO confirmed that T4MO catalyzes this initial reaction. The NTDMA produced by P. mendocina KR1 did not accumulate, but rather it was metabolized further to produce N-nitromethylamine (88 to 94% recovery) and a trace amount of formaldehyde (HCHO). Small quantities of methanol (CH3OH) were also detected when the strain was incubated with NDMA but not during incubation with either NTDMA or HCHO. The formation of methanol is hypothesized to occur via a second, minor pathway mediated by an initial alpha-hydroxylation of the nitrosamine. Strain KR1 did not grow on NDMA or mineralize significant quantities of the compound to carbon dioxide, suggesting that the degradation process is cometabolic. 相似文献
73.
Kovalcsik R Devlin T Loux S Martinek M May J Pickering T Tapp R Wilson S Serota D 《Lab animal》2006,35(9):49-53
Research scientists and IACUC members are faced with the difficult task of balancing the necessity of using animals for experimental research and their mandate to protect the welfare of those animals used in that research. One way to reduce the number of research animals would be to reuse them, but the regulations do not specifically address this topic. To learn more about the reuse of research animals, the authors conducted an online survey of animal facilities involved in preclinical studies. Their results suggest that animal reuse is a common practice in the field. 相似文献
74.
The migration of human microvascular endothelial cells (hMEC) was measured on a range of fibronectin gradient slopes. hMEC drift speed increased with increasing gradient slope with no concurrent change in cellular persistence time or random cell speed. The frequency of discrete cellular motion in the gradient direction increased with gradient slope. Morphological polarization of cells on the gradients is also characterized and correlated with cellular drift speed. These experiments present the first demonstration of cellular response to changing haptotactic gradient slope using an in vitro system for the quantitative study of cell migration. 相似文献
75.
Letavic MA Bronk BS Bertsche CD Casavant JM Cheng H Daniel KL George DM Hayashi SF Kamicker BJ Kolosko NL Norcia LJ Oberton VD Rushing MA Santoro SL 《Bioorganic & medicinal chemistry letters》2002,12(19):2771-2774
The stereoselective synthesis of two novel series of tribasic macrocyclic antibiotics with potent in vitro activity against Pasteurella multocida and Escherichia coli strains of bacteria is described. The in vitro activity can be significantly influenced by the nature of the substituents on the C-4" aminoalcohol, with the stereochemistry of the C-4" alcohol playing a less critical role. The effect of substitution and stereochemistry on the in vivo activity in a murine model of respiratory infection is also described. 相似文献
76.
Cingöz O Paprotka T Delviks-Frankenberry KA Wildt S Hu WS Pathak VK Coffin JM 《Journal of virology》2012,86(1):328-338
Xenotropic murine leukemia virus-related virus (XMRV) was previously reported to be associated with human prostate cancer and chronic fatigue syndrome. Our groups recently showed that XMRV was created through recombination between two endogenous murine retroviruses, PreXMRV-1 and PreXMRV-2, during the passaging of a prostate tumor xenograft in nude mice. Here, multiple approaches that led to the identification of PreXMRV-2, as well as the distribution of both parental proviruses among different mouse species, are described. The chromosomal loci of both proviruses were determined in the mouse genome, and integration site information was used to analyze the distribution of both proviruses in 48 laboratory mouse strains and 46 wild-derived strains. The strain distributions of PreXMRV-1 and PreXMRV-2 are quite different, the former being found predominantly in Asian mice and the latter in European mice, making it unlikely that the two XMRV ancestors could have recombined independently in the wild to generate an infectious virus. XMRV was not present in any of the mouse strains tested, and among the wild-derived mouse strains analyzed, not a single mouse carried both parental proviruses. Interestingly, PreXMRV-1 and PreXMRV-2 were found together in three laboratory strains, Hsd nude, NU/NU, and C57BR/cd, consistent with previous data that the recombination event that led to the generation of XMRV could have occurred only in the laboratory. The three laboratory strains carried the Xpr1(n) receptor variant nonpermissive to XMRV and xenotropic murine leukemia virus (X-MLV) infection, suggesting that the xenografted human tumor cells were required for the resulting XMRV recombinant to infect and propagate. 相似文献
77.
78.
Sonneville KR Rifas-Shiman SL Kleinman KP Gortmaker SL Gillman MW Taveras EM 《Obesity (Silver Spring, Md.)》2012,20(7):1449-1454
Relatively little research has assessed the association between obesogenic behaviors in parents and their children. The objective of the present analysis was to examine cross-sectional associations in television (TV)/video viewing, sugar-sweetened beverage intake, and fast food intake between mothers and their preschool aged children. We studied baseline data among 428 participants in High Five for Kids, a randomized controlled trial of behavior change among overweight and obese children of ages 2-6.9 years. The main exposures were whether mothers viewed TV/videos <1 h/day, drank <1 serving/day of sugar-sweetened beverages, and ate fast food <1 time/week. The main outcomes were whether children met these goals for the same behaviors. Using multivariate logistic regression adjusted for maternal and child characteristics, we estimated odds ratios of children meeting the behavioral goals. The majority of mothers ate fast food <1 time/week (73%) and drank <1 serving/day of sugar-sweetened beverages (73%), while few mothers viewed <1 h/day of TV/videos (31%). Most children met the fast food goal (68%), but not the goals for sugar-sweetened beverages (31%) or TV/video viewing (13%). In adjusted models, the odds ratios for a child meeting the goal were 3.2 (95% confidence interval (CI) 1.7, 6.2) for TV/video viewing, 5.8 (95% CI 2.8, 12.0) for sugar-sweetened beverage intake, and 17.5 (95% CI 9.8, 31.2) for fast food intake if their mothers met the goal for the same behavior. Obesogenic behaviors of mothers and preschool aged children were strongly associated. Our findings lend support to obesity prevention strategies that target parental behavior and the family environment. 相似文献
79.
Yone J. Yoon Sheryl L. White Xianglian Ni Alexander P. Gokin Miguel Martin-Caraballo 《PloS one》2012,7(11)
AMPA receptors lacking the GluA2 subunit allow a significant influx of Ca2+ ions. Although Ca2+-permeable AMPA receptors are a familiar feature at early stages of development, the functional significance of these receptors during the maturation of the nervous system remains to be established. Chicken lumbar motoneurons express Ca2+-permeable AMPA receptors at E6 but the Ca2+ permeability of AMPA receptors decreases ∼3-fold by E11. Considering that activity-dependent changes in intracellular Ca2+ regulates dendritic outgrowth, in this study we investigated whether downregulation of GluA2 expression during a critical period of development alters the dendritic arborization of spinal motoneurons in ovo. We use an avian replication-competent retroviral vector RCASBP (B) carrying the marker red fluorescent protein (RFP) and a GluA2 RNAi construct to downregulate GluA2 expression. Chicken embryos were infected at E2 with one of the following constructs: RCASBP(B)-RFP, RCASBP(B)-RFP-scrambled RNAi, or RCASBP(B)-RFP-GluA2 RNAi. Infection of chicken embryos at E2 resulted in widespread expression of RFP throughout the spinal cord with ≥60% of Islet1/2-positive motoneurons infected, resulting in a significant reduction in GluA2 protein expression. Downregulation of GluA2 expression had no effect on the dendritic arborization of E6 motoneurons. However, downregulation of GluA2 expression caused a significant reduction in the dendritic arborization of E11 motoneurons. Neither motoneuron survival nor maturation of network activity was affected by changes in GluA2 expression. These findings demonstrate that increased GluA2 expression and changes in the Ca2+ permeability of AMPA receptors regulate the dendritic arborization of spinal cord motoneurons during a critical period of development. 相似文献
80.
Maya N. Mascarenhas Seth R. Flaxman Ties Boerma Sheryl Vanderpoel Gretchen A. Stevens 《PLoS medicine》2012,9(12)