Hwa Sik Moon

Leaching characteristics of selected Korean fly ashes and its implications for the groundwater composition near the ash disposal mound

Abstract Currently only 20% of the fly ash produced in Korea is utilised for industry, and the remainder is disposed as waste in landfill sites. Both anthracite and sub-bituminous coals are burnt in Korea. Fly ash and coal samples were collected from five different coal-fired power stations in Korea and analysed for their chemistry and mineralogy. Batch leaching tests were also carried out to investigate the leaching behaviour of selected fly ashes. The fly ash leachate chemistry was compared with the groundwater taken directly from the monitoring well installed in one of the power stations. The anthracite coals contain illite, pyrophyllite and kaolinite whereas kaolinite is the representative clay mineral for the sub-bituminous coals. Anthracite coals were higher in Si, Al and K than the sub-bituminous coals, reflecting higher mineral matter contents in the anthracite coals. Mullite and quartz are the main mineral phases for two different types of the fly ashes, with some iron oxides. The chemical compositions of the anthracite and sub-bituminous fly ashes are comparable with each other, except for extraordinary high concentrations of Cr for one anthracite fly ash. Most of the trace elements in the ash were enriched in the finer fraction, indicating surface associations. Although, some elements including Na, K, Ca and Cu were released rapidly in the initial stage of leaching, measurable amounts of metals were still detectable in the fly ash leachate treated several times with distilled water. Such leaching behaviour indicates slow and long-term leaching of elements associated with the glass fractions of the ash particle. This was confirmed by leaching of weathered fly ash, which had been disposed of for several years. Comparison of the ash leachate, treated with 0.1N-HCl, fly ash slurry in the ash pond and the groundwater indicate the influence of the ash leachate from the ash disposal mound on the groundwater composition.

Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro. In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.

Expression of vascular endothelial growth factor and hypoxiainducible factor in the airway of asthmatic patients

BACKGROUND Vascular endothelial growth factor (VEGF) is a potent proangiogenic cytokine, and it also increases vascular permeability. It is well known that VEGF levels are increased in the airway of asthmatic patients. Hypoxia-inducible factor (HIF) induces a rapid and strong increase in VEGF expression. OBJECTIVES To evaluate the relationship between VEGF level and clinical characteristics and to determine whether VEGF expression is associated with HIF expression in asthmatic patients. METHODS Bronchoscopy was performed on 30 asthmatic patients and 14 control subjects. The concentration of VEGF in the bronchoalveolar lavage fluid (BALF) was examined using enzyme-linked immunosorbent assay. We measured VEGF, HIF-1alpha, and HIF-2alpha expression on biopsy specimens by means of immunoreactivity. RESULTS The VEGF level in the BALF was significantly higher in asthmatic patients than in controls. The VEGF level correlated with eosinophil counts in the BALF in asthmatic subjects (r = 0.501; P < .01). However, the VEGF level did not correlate with percentage of forced expiratory volume in 1 second and airway hyperresponsiveness. Asthmatic patients exhibited higher VEGF, HIF-1alpha, and HIF-2alpha immunoreactivity in the submucosa than did controls. Furthermore, VEGF expression correlated significantly with HIF-1alpha (r = 0.614; P = .02) and HIF-2alpha (r = 0.881; P = .001) expression. CONCLUSION These findings suggest that VEGF may play an important role in inflammation and that VEGF level is related to HIF in bronchial asthma.

Inhibitory effects of anti-immunoglobulin E antibodies on airway remodeling in a murine model of chronic asthma.

Background: Airway remodeling is one of the cardinal features of asthma and is thought to play a pivotal role in refractory or persistent asthma. Immunoglobulin E (IgE) has a major effect on the pathogenesis of asthma. The aim of this study was to investigate the effects of anti-IgE antibody not only on airway inflammation and bronchial hyperresponsiveness, but also on airway remodeling in a murine model of chronic asthma. Methods: The authors developed a mouse model of chronic asthma in which ovalbumin (OVA)-sensitized female BALB/c-mice were exposed to intranasal OVA administration twice a week for 3 months. Anti-IgE antibodies were administered intravenously starting on the 38th day and once a month thereafter for 3 months during the intranasal OVA challenge. Results: Mice that were chronically exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR) to methacholine and showed increased levels of collagen, hydroxyproline, and α-smooth muscle actin, as compared with control mice. Treatment with anti-IgE antibody inhibited the development of AHR, eosinophilic inflammation, and airway remodeling. Moreover, anti-IgE antibody treatment reduced the levels of interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluids, although it did not affect the levels of IL-10, transforming growth factor-β, and activin A. Conclusion: These results suggest that anti-IgE antibody treatment modulates the airway inflammation and remodeling associated with chronic allergen challenge. The inhibition of inflammation may be related to the regulation of Th2 cytokines. However, the mechanisms underlying the blocking of airway remodeling by anti-IgE antibody remain to be elucidated.

Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies.

IntroductionNeutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied.MethodsWe studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery.ResultsCompared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76).ConclusionsPatients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.

Effects of elastase inhibitor on the epithelial cell apoptosis in bleomycin-induced pulmonary fibrosis.

Alveolar epithelial cell injury and apoptosis is consistent findings in human idiopathic pulmonary fibrosis (IPF). Epithelial cell apoptosis is known to be induced by leukocyte elastase in vitro. The authors hypothesized that synthetic neutrophil elastase inhibitor, sivelestat (ONO-5046), can inhibit the bleomycin-induced pulmonary fibrosis in rats by blocking the apoptotic pathways in epithelial cells. Adult rats were injected with intratracheal bleomycin. Sivelestat was given for 13 days intraperitoneally after bleomycin treatments. Similar experiments were carried out in which A549 cells, a human alveolar type II epithelial cell line, were treated with bleomycin or neutrophil elastase. In rats, sivelestat decreased neutrophil counts and the cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage (BAL) fluid of bleomycin-treated rats. Sivelestat also decreased the bleomycin-induced lung inflammatory cell apoptosis by decreasing caspase-3 and -9 activities. In A549 cells, sivelestat decreased the elastase-induced epithelial cell apoptosis but not the bleomycin-induced epithelial cell apoptosis. Similarly, sivelestat inhibited the elastase-induced cell death but not the bleomycin-induced cell death in MTT assays. Sivelestat also inhibited the elastase-induced caspase-3 and -9 activities and cytochrome c release from the mitochondria but did not inhibit the bleomycin-induced caspase activities in A549 cells. In conclusion, bleomycin caused the lung inflammatory cell apoptosis through the caspase-9 and -3 pathways in rats. Sivelestat inhibited pulmonary fibrosis by blocking these mitochondria-mediated apoptotic pathways in bleomycin-treated rats and in elastase-treated A549 cells. These findings suggest that sivelestat can suppress the bleomycin-induced pulmonary fibrosis by blocking neutrophil chemotaxis and by inhibiting the neutrophil elastase–induced lung cell apoptosis in rats.

Effect of fudosteine on mucin production

Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-α-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-α. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK). MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-α in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-α, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.

The Soluble Tumor Necrosis Factor-Alpha Receptor Suppresses Airway Inflammation in a Murine Model of Acute Asthma

Purpose Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-α blocking strategies are now being tried in asthma patients. This study investigated whether TNF-α blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-α blocking therapy on cytokine production and adhesion molecule expression. Materials and Methods Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-α receptor (sTNFR) during the OVA challenge. Results There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue. Conclusion These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.

Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twenty-four hours later, bronchoalveolar lavage and histological examination were performed. The degree of overproduction of mucus, subepithelial fibrosis, and the thickness of the peribronchial smooth muscle in the experimental group was clearly increased compared to the control group. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was increased; during the twelfth week, the number of neutrophils increased in the experimental group. With regard to changes in cytokines, the concentrations of IL-4, IL-13, and transforming growth factor-beta (TGF-β) were increased in the experimental group. The data suggest that eosinophils, IL-4, IL-13, and TGF-β might play an important role in the airway remodeling process and that neutrophils may be involved with increased exposure time.

Time Sequence of Airway Remodeling in a Mouse Model of Chronic Asthma: the Relation with Airway Hyperresponsiveness

During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness.