Effective ion charge (Zeff) measurements and impurity behavior in KSTAR.

A visible bremsstrahlung detector array diagnostic system has been developed on the Korea Superconducting Tokamak Advanced Research (KSTAR) to view the whole minor radius in a narrow region of the continuum free of spectral lines. The interference filters coupled with photomultiplier tubes have been employed to determine the effective charge Zeff by using visible bremsstrahlung data during neutral beam injection in the KSTAR plasma. The Zeff profiles are typically flat for L-mode plasmas and evolve to hollow profiles during the H mode in the KSTAR. A comparison of the visible bremsstrahlung emission based on the calculated Zeff profiles is consistent with measured values of Zeff from a visible spectrometer in the core plasma. The electron temperature is measured by X-ray imaging crystal spectrometry, and electron density needed for the analysis is taken by the assumption of parabolic profiles of these parameters. The line of sight averaged local bremsstrahlung emissivity is determined with low uncertainty, and the radial emissivity is obtained by using the Abel inversion technique. In addition, a dependence of effective charge Zeff on the line-averaged electron density is evaluated, and Zeff is also determined to observe the effect of boronization.

15-deoxy-Δ12,14-prostaglandin J2 induces p53 expression through Nrf2-mediated upregulation of heme oxygenase-1 in human breast cancer cells.

Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that has antioxidant and cytoprotective functions. However, HO-1 has oncogenic functions in cancerous or transformed cells. In the present work, we investigated the effects of HO-1 on the expression of p53 induced by 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) in human breast cancer (MCF-7) cells. Treatment of MCF-7 cells with 15d-PGJ2 led to time-dependent increases in the expression of p53 as well as HO-1. Upregulation of p53 expression by 15d-PGJ2 was abrogated by si-RNA knock-down of HO-1. In MCF-7 cells transfected with HO-1 si-RNA, 15d-PGJ2 failed to induce expression of p53 as well as HO-1. In addition, HO-1 inducers enhanced the p53 expression. We speculated that iron, a by-product of HO-1-catalyzed reactions, could mediate 15d-PGJ2-induced p53 expression. Upregulation of p53 expression by 15d-PGJ2 was abrogated by the iron chelator desferrioxamine in MCF-7 cells. Iron released from heme by HO-1 activity is mostly in the Fe(2+) form. When MCF-7 cells were treated with the Fe(2+)-specific chelator phenanthroline, 15d-PGJ2-induced p53 expression was attenuated. In addition, levels of the Fe-sequestering protein H-ferritin were elevated in 15d-PGJ2-treated MCF-7 cells. In conclusion, upregulation of p53 and p21 via HO-1 induction and subsequent release of iron with accumulation of H-ferritin may confer resistance to oxidative damage in cancer cells frequently challenged by redox-cycling anticancer drugs.

Diagnostic sensitivity of culture and drug resistance patterns in Korean patients with intestinal tuberculosis.

SETTING: It is challenging to differentiate between intestinal tuberculosis (ITB) and Crohn's disease in areas where TB is still prevalent. The use of diagnostic tools and verifying the drug resistance patterns of ITB can be helpful for its correct diagnosis. OBJECTIVE: To determine the diagnostic sensitivity of a culture assay using colonoscopic biopsy specimens and the drug resistance patterns of Mycobacterium tuberculosis isolated from ITB. DESIGN: Data from 400 patients diagnosed with ITB were retrospectively analysed. RESULTS: Of the 400 patients, 170 (42.5%) were males; the median age at diagnosis was 40 years. The sensitivity of culture was 44.1% (145/329). Resistance to at least one anti-tuberculosis drug was identified in 13 (17.6%) and multidrug-resistant TB (MDR-TB) was diagnosed in two (2.7%) of the 74 patients for whom drug susceptibility testing was performed. Including M. tuberculosis isolated from respiratory specimens, the proportion of MDR-TB was 4.4% (5/113); previous anti-tuberculosis treatment was an independent risk factor for MDR-TB (26.7% vs. 1.0%, P < 0.01). CONCLUSION: Culture of colonoscopic biopsy specimens shows substantial diagnostic sensitivity; the frequency of MDR-TB is higher in previously treated cases than in new cases.

Diagnostics for first plasma and development plan on KSTAR.

The first plasma with target values of the plasma current and the pulse duration was finally achieved on June 13, 2008 in the Korea Superconducting Tokamak Advanced Research (KSTAR). The diagnostic systems played an important role in achieving successful first plasma operation for the KSTAR tokamak. The employed plasma diagnostic systems for the KSTAR first plasma including the magnetic diagnostics, millimeter-wave interferometer, inspection illuminator, H(alpha), visible spectrometer, filterscope, and electron cyclotron emission (ECE) radiometer have provided the main plasma parameters, which are essential for the plasma generation, control, and physics understanding. Improvements to the first diagnostic systems and additional diagnostics including an x-ray imaging crystal spectrometer, reflectometer, ECE radiometer, resistive bolometer, and soft x-ray array are scheduled to be added for the next KSTAR experimental campaign in 2009.

15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue.

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative cyclopentenone prostaglandin, has many interesting biological effects. In this study, treatment of human breast cancer cells (MCF-7) with 15d-PGJ(2) led to accumulation of p53 protein. However, the p53 DNA binding and its transcriptional activity were significantly reduced. 15d-PGJ(2) directly modified p53 as verified by reacting recombinant p53 with biotinylated 15d-PGJ(2). 9,10-Dihydro-15-deoxy-Delta(12,14)-prostaglandin J(2) lacking the electrophilic alpha,beta-unsaturated functionality failed to inhibit p53 DNA binding as well as to modify p53. Moreover, by conducting an in vitro [(35)S]-labeled p53 translation assay, we identified cysteine 277 as a putative site of p53 modification by 15d-PGJ(2). The DNA-binding ability of a mutant p53 in which cysteine 277 was substituted by alanine was virtually unaffected by 15d-PGJ(2). Likewise, p53 binding activity of biotinylated 15d-PGJ(2) was abolished in mutant cells. In addition, cells expressing wild-type p53 exhibited p53 protein stability to a greater extent than mutant C277A cells. In conclusion, 15d-PGJ(2) can undergo nucleophilic addition to p53, presumably at the cysteine 277 residue, rendering this tumor suppressor less susceptible to proteasomal degradation.

Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer.

Recently, there have been considerable efforts to search for naturally occurring substances that can inhibit, reverse, or retard the multi-stage carcinogenesis. A wide array of phenolic substances derived from edible and medicinal plants have been reported to possess anticarcinogenic and antimutagenic activities and in many cases, the chemopreventive activities of phytochemicals are associated with their anti-inflammatory and/or antioxidative properties. Panax ginseng C.A. Meyer cultivated in Korea has been widely used in traditional herbal medicine for the treatment of various diseases. Certain fractions or purified ingredients of ginseng have been shown to exert anticarcinogenic and antimutagenic activities. Our previous studies have revealed that the methanol extract of heat-processed Panax ginseng C.A. Meyer attenuates the lipid peroxidation in rat brain homogenates and is also capable of scavenging superoxide generated by xanthine- xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of the same extract onto shaven backs of female ICR mice also suppressed TPA-induced skin tumor promotion. Likewise, topical application of ginsenoside Rg3, one of the constituents of heat-treated ginseng, significantly inhibited TPA-induced mouse epidermal ornithine decarboxylase activity and skin tumor promotion. Expression of cyclooxygenase-2 (COX-2) in TPA-stimulated mouse skin was markedly suppressed by Rg3 pretreatment. In addition, Rg3 inhibited TPA-stimulated activation of NF-kappaB and extracellular-regulated protein kinase (ERK), one of the mitogen-activated protein (MAP) kinase in mouse skin and also in cultured human breast epithelial cells (MCF-10A).

Restoration of gap junctional intercellular communication by caffeic acid phenethyl ester (CAPE) in a ras-transformed rat liver epithelial cell line.

Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having anti-inflammatory, anti-viral and anti-cancer properties. Since the deficiency of gap junctional intercellular communication (GJIC) has been shown to be a characteristic of most cancer cells, this study was designed to test the hypothesis that the anti-carcinogenic activity of CAPE might be related to its ability to restore GJIC in tumorigenic GJIC-deficient cells (WB-ras2 cells). The results showed that CAPE restored GJIC, phosphorylation of connexin 43 (Cx43) and its normal localization on the plasma membrane in WB-ras2 cells after 3 days at 5 microg/ml concentration. Additionally, CAPE inhibited growth in soft agar and decreased the protein level of p21(ras). The results are consistent with the hypothesis that the anti-cancer mechanism of CAPE may be mediated by its ability to restore GJIC.

Lambda-carrageenan-induced inhibition of gap-junctional intercellular communication in rat liver epithelial cells.

lambda-Carrageenan, a food additive extracted from red seaweed, is widely used as an emulsifier, stabilizer, or thickener. Previously, it has been shown that carrageenan could play a role in carcinogenesis. However, the mechanism by which it might influence the multimechanism, multistep process of carcinogenesis is not known. Gap-junctional intercellular communication (GJIC) has been associated with maintaining homeostatic regulation of cell proliferation and differentiation. Most cancer cells have dysfunctional GJIC, and many tumor-promoting chemicals, growth factors, and oncogenes can downregulate GJIC. The experiments in this study were designed to test the hypothesis that carrageenan might function as a tumor-promoting chemical by inhibiting GJIC. To test this hypothesis, nontumorigenic rat liver epithelial cells were exposed to carrageenan, and GJIC was measured. Western blot analysis and immunofluorescent staining were used to monitor the phosphorylation and localization of connexin 43. The data revealed inhibition of GJIC by carrageenan similar to that by the well-documented tumor promoter phorbol ester. However, the phosphorylation and localization of connexin 43 were not altered. Although the mechanism by which carrageenan inhibits GJIC is unknown, carrageenan's influence on the carcinogenic process might be via its ability to be a tumor promoter.

Self-assembling nanospheres of hydrophobized pullulans in water.

In this report, we have prepared self-assembling nanospheres of hydrophobized pullulans. Pullulan acetate as a hydrophobized pullulan was synthesized by acetylation of pullulan and characterized by Fourier transform infrared (FTIR) measurement. From the results of photon correlation spectroscopy (PCS), hydrophobized pullulans could be self-assembled in water as nanospherical aggregates, and their number-average particle size was 74.3 +/- 38.2 nm with a unimodal distribution. Also, morphological studies observed by transmission electron microscopy (TEM) showed that self-assembly of hydrophobized pullulans results in nice spherical shapes with a size range of about 50-100 nm, which was in accordance with PCS measurements. Their size and morphology have acceptable properties for intravenous injectable drug-targeting carriers. The fluorescence probe technique was used for self-association of hydrophobized pullulans in water using pyrene as a hydrophobic probe. From the fluorescence measurement, the fluorescence intensity of pyrene increased with increasing concentration of hydrophobized pullulans, which indicates self-assembly formation of hydrophobized pullulans in water. Also, in the fluorescence excitation spectrum, a red shift was observed with increasing concentration of hydrophobized pullulans. These results also revealed that hydrophobized pullulans could be self-assembled in water, and from the plot of I337/I334 versus log c of hydrophobized pullulans, the critical association concentration was 0.0022 g/l, which was considerably lower than that of low molecular weight surfactants or poloxamer. A drug loading study was performed using clonazepam (CNZ) as a hydrophobic model drug. We observed that the higher the feeding amount of drug was, the more the drug loading contents were, the lower the drug loading efficiency was, and the larger the particle size was. CNZ was released from nanospheres via pseudo-zero-order kinetics, and the increased drug loading contents led to slower release of the drug.

High-performance liquid chromatographic determination of trimebutine and its major metabolite, N-monodesmethyl trimebutine, in rat and human plasma.

A rapid, selective and very sensitive ion-pairing reversed-phase HPLC method was developed for the simultaneous determination of trimebutine (TMB) and its major metabolite, N-monodesmethyltrimebutine (NDTMB), in rat and human plasma. Heptanesulfonate was employed as the ion-pairing agent and verapamil was used as the internal standard. The method involved the extraction with a n-hexane-isopropylalcohol (IPA) mixture (99:1, v/v) followed by back-extraction into 0.1 M hydrochloric acid and evaporation to dryness. HPLC analysis was carried out using a 4-microm particle size, C18-bonded silica column and water-sodium acetate-heptanesulfonate-acetonitrile as the mobile phase and UV detection at 267 nm. The chromatograms showed good resolution and sensitivity and no interference of plasma. The mean recoveries for human plasma were 95.4+/-3.1% for TMB and 89.4+/-4.1% for NDTMB. The detection limits of TMB and its metabolite, NDTMB, in human plasma were 1 and 5 ng/ml, respectively. The calibration curves were linear over the concentration range 10-5000 ng/ml for TMB and 25-25000 ng/ml for NDTMB with correlation coefficients greater than 0.999 and with within-day or between-day coefficients of variation not exceeding 9.4%. This assay procedure was applied to the study of metabolite pharmacokinetics of TMB in rat and the human.