Establishment of a new animal model of azithromycin-induced liver injury and study the molecular pathological change during the process.

The purpose of the present study is to establish a new animal model of azithromycin (AZ)-induced liver injury and study the molecular pathological change during the process. First, mice were respectively injected intraperitoneally with AZ of different high doses. Our results showed that 800 mg/kg AZ injection significantly induced liver injury in the mice, which reflected an ideal process of liver injury and repair. In this study, we analyzed the molecular pathological changes during the process by hematoxylin and eosin staining, immunohistochemistry, Western blot, and quantitative real-time reverse transcription polymerase chain reaction in the liver of mice at 0, 12, 24, 48, and 72 h after 800 mg/kg injection. Our results showed that the expression of heat shock protein 70, proliferating cell nuclear antigen, vascular endothelial growth factor, caspase 3, and cytochrome P450 2E1 were significantly differently expressed during liver injury induced by 800 mg/kg AZ in mice. Our results will be conducive for further study of the pathogenesis and prevention of drug-induced liver injury.

Clinical and genetic characterization of complete androgen insensitivity syndrome in a Chinese family.

We studied a family with two cousins who were diagnosed with complete androgen insensitivity syndrome, an X-linked disorder caused by mutations in the androgen receptor gene. A pedigree analysis and a molecular study using PCR and DNA sequencing clarified each female family member's androgen receptor status and revealed a mutation consisting of the deletion of exon 2 and surrounding introns of the androgen receptor gene. Based on the relative nucleotide positions, we concluded that the deletion mutation in exon 2 and its surrounding introns was approximately 6000 to 7000 bp. This mutation, never previously fully characterized using DNA sequencing, was responsible for complete androgen insensitivity syndrome in this family. Pedigree analysis with a molecular study of the androgen receptor gene in affected families facilitates genetic counseling provided to family members.

Disruption of glucose homeostasis and induction of insulin resistance by elevated free fatty acids in human L02 hepatocytes.

Free fatty acids (FFA) have been implicated as an important causative link between obesity, insulin resistance, and Type 2 diabetes. However, the underlying mechanisms especially for FFA-mediated hepatic insulin resistance are not fully elucidated. Here, we investigated the impaired sites in insulin signaling pathways and mechanisms of insulin resistance induced by elevated FFA in L02 hepatocytes. L02 cells were cultured in Dulbecco's modified eagle medium containing various concentrations of palmitic acid (PA) for 24 h followed by 10(-7) mol/l insulin stimulation. In some experiments, cells were pre-treated with enzymatic inhibitor Wortmannin (10(-6) mol/l). Glucose levels in medium, cytosolic glycogen contents, and phosphoenolpyruvate carboxykinase (PEPCK) activity were measured. Protein level of insulin receptor substrate (IRS)-2 and phosphorylated Akt were detected by Western blot analysis. L02 cells treated with high levels of PA exhibited increased glucose levels, whereas hepatic glycogen contents were decreased in a dose-dependent manner as compared to the control cells. There was a significant attenuation of IRS- 2 protein expression in the cells cultured with PA, and Wortmannin intervention exhibited different IRS-2 protein level with or without PA treatment. In accordance with the reduced IRS-2 level, the insulin-stimulated phosphorylation of Akt was diminished in the PA-treated cells. Basal PEPCK activity and insulin- regulated PEPCK activity were overstimulated in the cells incubated with PA. These data indicate high levels of FFA can disrupt glucose homeostasis, inflict some defects in insulin signaling, and induce insulin resistance in L02 cells.

Adsorption, attachment and biofilm formation among isolates of Listeria monocytogenes using model conditions.

AIMS: To determine whether isolates of Listeria monocytogenes differ in their ability to adsorb and form biofilms on a food-grade stainless steel surface. METHODS AND RESULTS: Strains were assessed for their ability to adsorb to a test surface over a short time period. Although some differences in numbers of bound cells were found among the strains, there were no correlations between the degree of adsorption and either the serotype or source of the strain. The ability of each strain to form a biofilm when grown with the test surface was also assessed. With the exception of a single strain, all strains adhered as single cells and did not form biofilms. Significant differences in adherence levels were found among strains. Strains demonstrating enhanced attachment produced extracellular fibrils, whereas those which adhered poorly did not. A single strain formed a biofilm consisting of adhered single cells and aggregates of cells. CONCLUSIONS: Significant differences were found in the ability of various L. monocytogenes strains to attach to a test surface. In monoculture, the majority of strains did not form biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Differences in attachment and biofilm formation among strains provide a basis to study these characteristics in L. monocytogenes.

An Assessment of Source Contributions to Ambient Aerosols in Central Taiwan.

Ambient aerosols were sampled at three selected sites in the coastal region of central Taiwan to obtain composition data for use in receptor modeling. All the samples were analyzed for 20 elements with an x-ray fluorescence spectrometer. The mass percentage of sulfates in particle samples was determined by ion chromatography, and mass percentages of elemental carbon (EC) and organic carbon (OC) were determined by an elemental analyzer. Because the three sampling sites were located within 25 km of each other, the average chemical compositions were similar for particle samples taken at the three sites on the same day. However, the variation in composition from day to day was significantly influenced by wind direction and change in local sources, such as the burning of agricultural wastes. The abundant species in the coarse fraction (2.5-10 µm) were Al (0.5-4.0 µg/m3), Cl (0.1-4.8 µg/m3), Ca (0.2-3.4 µg/m3), Fe (0.2-2.8 µg/ m3), and K (0.1-1.4 µg/m3), while the abundant species in the fine fraction (<2.5 µm) were S (0.3-3.5 µg/m3), Cl (0.01-1.9 µg/ m3), K (0.04-0.98 µg/m3), organic carbon (0.01-10.5 µg/m3), elemental carbon (0-10.7 µg/m3), and sulfates (1.2-15.7 µg/m3). Calculations for source apportionment were carried out using the CMB7 software developed by the U.S. Environmental Protection Agency (EPA). The main sources for the coarse fraction of ambient aerosols in the region were found to be marine aerosol, coal and fuel oil combustion, burning of agricultural wastes, and paved road dust. The main sources for the fine fraction were burning of agricultural wastes, diesel exhaust, coal and oil combustion, and sulfates. Source apportionment for the fine fraction was relatively sensitive to the types of sources selected for calculations and the compositions of the sources. The problem can be ameliorated by careful examination of possible sources and by use of local source profiles.