• Title/Summary/Keyword: dose distribution

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A Novel Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivative, N25, Exhibiting Improved Antitumor Activity in both Human U251 and H460 Cells

  • Zhang, Song;Huang, Wei-Bin;Wu, Li;Wang, Lai-You;Ye, Lian-Bao;Feng, Bing-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4331-4338
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    • 2014
  • $N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

Pattern on Ascaris lumbricoides Infection in a Rural Area of Keread (한국농촌(韓國農村)에 있어서의 회충감염상(蛔虫感染相))

  • Lee, Joon-Sang;Kim, Kwang-Rock;Ko, Dae-Kyoung;Sung, Dae-Rim;Lee, Ja-Young;Rim, Han-Jong
    • Journal of agricultural medicine and community health
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    • v.5 no.1
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    • pp.28-33
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    • 1980
  • This study was undertaken to evaluate the present status of A. lumbricoides infection in a rural area of Korea. The 307 residents of all age group in Gumsa Myun, Yeo Ju Gun were examined by Kato's cellophane thick smear technique. Pyrantel pamoste was administered to the Ascaris infection cases by a single dose of 5mg/kg of body weight. The whole amount of 24 hour stool during two or three consecutive days were collected sepatately. The expelled A. lumbricoides worms from the unfiltered stool remnants were collected. They were measured by the length and weight, and the sex of the worms were differentiated. The results are as follows: 1) The incidence of A. lumbricoids infection of the 307 specimens examined was 40.1%(male: 40.9%, female:39.0%). The difference according to guman sex distribution was not statistically significant. 2) Seventy two Ascaris infected cases expelled 163 worms of various size. The mean number of worms per infected case were calculated as 2.3. The sex ratio of examined female and male Ascaris was 1.5:1 3) Among the expelled 97 female worms, the genital girdle were found in 60 female worms(61.9%). Genital girdle of gemale worm was located from the head in the position of $38{\pm}4$ of total length 100. 4) The average body length of male Ascaris was $16.3{\pm}3.1cm$ and female Ascaris was $21.7{\pm}3.5cm$ 5) The relationship between the weight(Y) and the length(X) of individual Ascaris worm was plotted. Y(gm).0.32$\fallingdotseq$(cm)-3.1 in female and Y(gm)$\fallingdotseq$0.1X(cm)-0.1 in male.

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The Literature Study on Macula among the Symptoms of Warm Factor Disease (온병(溫病)의 증상(症狀) 중(中) 반진(斑疹)에 관(關)한 문헌적(文獻的) 고찰(考察))

  • Jang, Yunjeong;Ryu, Sangchae;Kim, Jeongsoon;Jeon, Hoseong;Yu, Donghee;Kim, Nanyeong;Chong, Myongsoo;Lee, Kinam
    • Journal of Korean Medical Ki-Gong Academy
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    • v.11 no.1
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    • pp.80-116
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    • 2009
  • It studies into viewpoints of 7 doctors of Wenbing studies on macula. The results concerning characteristics, remedy and prevention of macula are as follows; Macule does not protrude on the surface of skin and does not have any color change for external stimulus, but rash out on the surface and becomes white when pushed. It becomes macule when the blood leaks beneath skin as stomach-heat of yangming enters into blood system and damages it. On the other hand, when heat enters lung meridian, penetrates beneath the skin and congeals inside the vessel, it becomes rash. When you combine symptoms of body and pulse with numbers, color, shape and distribution status of macula, you can diagnose the depth of rash, seriousness, the possibility of treatment and prognosis of macula. The remedy for macule consists of cooling heat of yaming, removing heat from the blood and relieving feverish rash, and the one for rash consists of facilitating meridian with aroma, expelling pathogenic factors from muscles with drugs of pungent flavor and cool nature and clearing away heat from the blood systems. It relieves the inhibited functional activities of lung-Ki, and helps extermination of rash as well as clearing heat of the vessel. Also, it is the most important to preserve resin of stomach for every treatment. It is good to avoid expelling pathogenic factors with drugs of pungent flavor and warm nature, raising drugs and invigorating drugs during treating macula. Moreover, the patients should not over dose cold-natured drugs and purgative therapy. There are common clinical symptoms of macula in advance, so right recognition of symptoms can contribute to prevention of macula.

The Fabrication and Evaluation of HgI2 Semiconductor Detector as High Energy X-ray Dosimeter Application (고에너지 X선 선량계 적용을 위한 TiO2 첨가된 요오드화수은 반도체 검출기 제작 및 평가)

  • Choi, Il Hong;Noh, Sung Jin;Park, Jung Eun;Park, Ji Koon;Kang, Sang Sik
    • Journal of the Korean Society of Radiology
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    • v.8 no.7
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    • pp.383-387
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    • 2014
  • In this paper, for a new detection system development with the better accurate dose evaluation and beam distribution imaging using the small field irradiation of linear accelerator, the compound semiconductor based detection sensors were fabricated and the performance evaluation was investigated. The special particle-in-binder sedimentation was used for a large area film sensor fabrication. The detection properties for high energy x-rays were investigated from a dark current, an output current, a rising time, a falling time, and response delay measurement. The experimental results, the $TiO_2$ mixed $HgI_2$ sensor showed the best electrical characteristics than $PbI_2$, PbO, pure $HgI_2$. Linearity, repeatability, and accuracy tests from LINAC were tested, the $TiO_2$ mixed $HgI_2$ sensor showed the better performance than the commercially available dosimetry devices.

Human Lung Insults due Air Pollutant -A Review for Priority Setting in the Research- (대기오염에 의한 폐장조직 손상 -연구방향의 설정을 위한 논의-)

  • 김건열;백도명
    • Journal of environmental and Sanitary engineering
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    • v.7 no.2
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    • pp.95-110
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    • 1992
  • Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

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Matrine Reduces Proliferation of Human Lung Cancer Cells by Inducing Apoptosis and Changing miRNA Expression Profiles

  • Liu, Yong-Qi;Li, Yi;Qin, Jie;Wang, Qian;She, Ya-Li;Luo, Ya-Li;He, Jian-Xin;Li, Jing-Ya;Xie, Xiao-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2169-2177
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    • 2014
  • Matrine, a main active component extracted from dry roots of Sophora flavecens, has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and timedependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.

Distribution of Microflora in Powdered Raw Grains and Vegetables and Improvement of Hygienic Quality by Gamma Irradiation (유통 생식제품의 미생물 분포 및 감마선 조사를 이용한 위생화)

  • Kim, Dong-Ho;Song, Hyun-Pa;Yook, Hong-Sun;Chung, Young-Jin;Kim, Yeung-Ji;Byun, Myung-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.4
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    • pp.589-593
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    • 2002
  • Improvement of hygienic quality of powdered raw grains and vegetables by gamma irradiation was investigated. Five products of powdered raw grains and vegetables were collected in a local market and analysed. The total viable cell counts of Bacillus were 10$^4$~10$^{7}$ cfu/g, filamentous fungi l0$^2$~10$^3$cfu/g, coliform 10$^1$~10$^4$cfu/g, enteric bacteria on SS agar plate 10$^1$~10$^3$cfu/g. Coliform, enteric bacteria on SS agar plate and filamentous fungi were eliminated by 3 kGy of gamma irradiation. The D values of coliform, enteric bacteria on SS agar plate, Bacillus, and filamentous fungi were 0.68~0.80 kGy, 0.59~0.74 kGy, 1.84~2.18 kGy and 0.36~0.57 kGy, respectively. It was considered that optimal irradiation dose for radappertization was about 25 kGy, while 3~5 kGy of gamma irradiation was effective for radicidation.

Engineering Characteristics of Ultra High Strength Concrete with 100 MPa depending on Fine Aggregate Kinds and Mixing Methods (잔골재 종류 및 혼합방법 변화에 따른 100 MPa 급 초고강도 콘크리트의 공학적 특성)

  • Han, Min-Cheol;Lee, Hong-Kyu
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.2
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    • pp.536-544
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    • 2016
  • Recently, with the increase in the number of high rise and huge scaled buildings, ultra-high strength concrete with 80~100 MPa has been used increasingly to withstand excessive loads. Among the components of concrete, the effects of the kinds and properties of fine aggregates on the performance and economic advantages of ultra-high strength concrete need to be evaluated carefully. Therefore, this study examined the effects of the type of fine aggregates and mixing methods on the engineering properties of ultra-high strength concrete by varying the fine aggregates including limestone fine aggregate (LFA), electrical arc slag fine aggregate (EFA), washed sea sand (SFA), and granite fine aggregate (GFA) and their mixtures. Ultra-high strength concrete was fabricated with a 20 % water to binder ratio (W/B) and incorporated with 70 % of Ordinary Portland cement: 20 % of fly ash:10 % silica fume. The test results indicate that for a given superplasticizer dose, the use of LFA resulted in increases in slump flow and L-flow compared to the mixtures using other aggregates due to the improved particle shape and grading of LFA. In addition, the use of LFA and EFA led to enhanced compressive strength and a decrease in autogenous shrinkage due to the improved elastic properties of LFA and the presence of free-CaO in EFA, which resulted in the formation of C-S-H.

A Study on the Optimization of Heat Flux in Engine Room of Auxiliary Power Unit for Self-Propelled Artillery (자주포용 보조동력장치 엔진룸의 열유동 최적화에 관한 연구)

  • Noh, Sang Wan;Park, Young Min;Kim, Sung Hoon;Lee, Jae Dong;Kim, Byung Hyun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.12
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    • pp.629-635
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    • 2019
  • In this study, we analyzed the effect of FAN and oil cooler application on APU. MIL-STD-810 was applied to the atmospheric environment and radiation dose in order to perform thermal flow analysis. The heat flow was analyzed for the case in which the inlet / outlet fan was applied (Case 1), the case in which the inlet fan and the oil cooler were applied (Case 2), and the case in which the inlet / outlet fan and the oil cooler were applied (Case 3). As a result, it was confirmed that the cylinder head temperature of Case 3 was 21.4 times lower than that of Case 1 and 8.0 times lower than that of Case 2. Experiments were conducted under the same ambient conditions in order to examine the validity of the results. The numerical values and experimental results showed a difference of less than 7%. Through this, we were able to confirm that the APU heat flow optimization model satisfies the design conditions. The results of this study are expected to be used as basic data for optimizing heat flow of APU.

Usefulness of serum cystatin C to determine the dose of vancomycin in neonate

  • Shin, Jeong Eun;Lee, Soon Min;Eun, Ho Seon;Park, Min Soo;Park, Kook In;Namgung, Ran
    • Clinical and Experimental Pediatrics
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    • v.58 no.11
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    • pp.421-426
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    • 2015
  • Purpose: The vancomycin dosage regimen is regularly modified according to the patient's glomerular filtration rate (GFR). In the present study, we aimed to assess the usefulness of serum cystatin C (Cys-C) concentration, compared with serum creatinine (SCr) concentration, for predicting vancomycin clearance (CLvcm) in neonates. Methods: We retrospectively analyzed the laboratory data of 50 term neonates who were admitted to the neonatal intensive care unit and received intravenous vancomycin, and assessed the pharmacokinetic profiles. Creatinine clearance (CLcr) and GFR based on Cys-C (GFRcys-c) were estimated using the Schwartz and Larsson formulas, respectively. Results: The mean CLvcm (${\pm}$standard deviation) was $74.52{\pm}31.17L/hr$, the volume of distribution of vancomycin was $0.67{\pm}0.14L$, and vancomycin half-life was $9.16{\pm}17.42hours$. The SCr was $0.46{\pm}0.25mg/dL$ and serum Cys-C was $1.43{\pm}0.34mg/L$. The peak and trough concentrations of vancomycin were $24.65{\pm}14.84$ and $8.10{\pm}5.35mcg/mL$, respectively. The calculated GFR based on serum creatinine concentration (GFR-Cr) and GFRcys-c were $70.2{\pm}9.45$ and $63.6{\pm}30.18mL/min$, respectively. The correlation constant for CLvcm and the reciprocal of Cys-C (0.479, P=0.001) was significantly higher than that for CLvcm and the reciprocal of SCr (0.286, P=0.044). GFRcys-c was strongly correlated with CLvcm (P=0.001), and the correlation constant was significantly higher than that for CLvcm and CLcr (0.496, P=0.001). Linear regression analysis showed that only GFRcys-c was independently and positively correlated with CLvcm (F=41.9, P<0.001). Conclusion: The use of serum Cys-C as a marker of CLvcm could be beneficial for more reliable predictions of serum vancomycin concentrations, particularly in neonates.