• Title/Summary/Keyword: Dose-dependency

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Cytotoxic Effects of Nanoparticles Assessed In Vitro and In Vivo

  • Cha, Kyung-Eun;Myung, Hee-Joon
    • Journal of Microbiology and Biotechnology
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    • v.17 no.9
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    • pp.1573-1578
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    • 2007
  • An increasing number of applications is being developed for the use of nanoparticles in various fields. We investigated possible toxicities of nanoparticles in cell culture and in mice. Nanoparticles tested were Zn (300 nm), Fe (100 nm), and Si (10-20, 40-50, and 90-110 nm). The cell lines used were brain, liver, stomach, and lung from humans. In the presence of nanopaticles, mitochodrial activity decreased zero to 15%. DNA contents decreased zero to 20%, and glutathione production increased zero to 15%. None of them showed a dose dependency. Plasma membrane permeability was not altered by nanoparticles. In the case of Si, different sizes of the nanoparticles did not affect cytotoxicity. The cytotoxicity was also shown to be similar in the presence of micro-sized ($45\;{\mu}m$) Si particles. Organs from mice fed with nanoparticles showed nonspecific hemorrhage, lymphocytic infiltration, and medullary congestion. A treatment with the micro-sized particle showed similar results, suggesting that the acute in vivo toxicity was not altered by nano-sized particles.

Grape Seed Extract Protects Mice against Disseminated Candidiasis

  • Han, Yong-Moon
    • Natural Product Sciences
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    • v.9 no.2
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    • pp.60-63
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    • 2003
  • Effect of grape seed extract (GSE) against Candida albicans was examined under in-vitro and in-vivo conditions. The GSE was extracted in ethanol. In-vitro results from an agar diffusion susceptibility assay showed the GSE inhibited C. albicans growth. This anticandidal effect was at dose-dependency. In experiments with animals, mice that received the GSE (0.5 mg per mice), intravenously (i.v.), before i.v.-infection wish viable C. albicans yeast cells survived longer than diluent (buffer)-received control mice. In contrast, when GSE was given to mice after the mice were infected with the yeast cells, these mice showed a similar survival rate as compared to control mice that received no treatment with the GSE. Taken together, these data indicate that GSE has prophylactic effect but not therapeutic effect against disseminated candidiasis.

The Effect on Antioxidant for Improving to Radiation Resistance on Irradiated PVDF (PVDF의 내방사선 특성 향상을 위한 산화방지제 첨가효과)

  • Kim, Ki-Yup;Lee, Chung;Ryu, Boo-Hyung;Lim, Kee-Joe
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2005.07a
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    • pp.252-253
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    • 2005
  • The dielectric relaxation properties of $^{60}Co$ gamma-ray irradiated Poly(vinylidene fluoride) (PVDF) containing various antioxidants have been investigated for radiation degradation. Cole-Cole's circular arcs were induced from the results of temperature and frequency dependency of dielectric properties with radiation dose. The magnitude of polarization of PVDF was decreased by adding antioxidants. The values of dielectric relaxation intensity calculated by using the Cole-Cole's circular arcs showed a certain tendency for radiation degradation.

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Dosimetric Characterization of an Ion Chamber Matrix for Intensity Modulated Radiation Therapy Quality Assurance (세기변조방사선치료 선량분포 확인을 위한 2차원적 이온전리함 배열의 특성분석)

  • Lee, Jeong-Woo;Hong, Se-Mie;Kim, Yon-Lae;Choi, Kyoung-Sik;Jung, Jin-Beom;Lee, Doo-Hyun;Suh, Tae-Suk
    • Progress in Medical Physics
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    • v.17 no.3
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    • pp.131-135
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    • 2006
  • A commercial ion chamber matrix was examined the characteristics and its performance for radiotherapy qualify assurance. The device was the I'mRT 2D-MatriXX (Scanditronix-Wellhofer, Schwarzenbruck, Germany). The 2D-MatriXX device consists of a 1020 vented ion chamber array, arranged in $24{\times}24cm^2$ matrix. Each ion chamber has a volume of $0.08cm^3$, spacing of 0.762 cm and minimum sampling time of 20 ms. For the investigation of the characteristics, dose linearity, output factor, short-term reproducibility and dose rate dependency were tested. In the testing of dose linearity. It has shown a good signal linearity within 1% in the range of $1{\sim}800$cGy. Dose rate dependency was found to be lower than 0.4% (Range: 100-600 Mu/min) relative to a dose rate of 300 Mu/min as a reference. Output factors matched very well within 0.5% compared with commissioned beam data using a ionization chamber (CC01, Scanditronix-Wellhofer, Schwarzenbruck, Germany) in the range of field sizes $3{\times}3{\sim}24{\times}24cm^2$. Short-term reproducibility (6 times with a interval of 15 minute) was also shown a good agreement within 0.5%, when the temperature and the pressure were corrected by each time of measurement. in addition, we compared enhanced dynamic wedge (EDW, Varian, Palo Alto, USA) profiles from calculated values in the radiation planning system with those from measurements of the MatriXX. Furthermore, anon-uniform IMRT dose fluence was tested. All the comparison studies have shown good agreements. In this study, the MatriXX was evaluated as a reliable dosimeter, and it could be used as a simplistic and convenient tool for radiotherapy qualify assurance.

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Comparison of Treatment Plans with Multileaf Collimators of different Leaf Width (Leaf width가 다른 다엽 콜리메터에 의한 치료계획 비교)

  • Kim Joo Young;Park Sung Yong;Lee Doo Hyun;Lee Seok Ho;Kim Tae Hyun;Cho Kwan Ho
    • Progress in Medical Physics
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    • v.15 no.4
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    • pp.173-178
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    • 2004
  • Purpose: To compare desimetrically intensity-modulated radiotherapy treatment plans with commercially available multileaf collimators (MLCs) of different leaf width for intracranial lesions. Materials and Methods: Twelve patients with intracranial lesions were treated with BrainLAB's micro-MLCs (mMLCs) and performed with the BrainSCAN ver. 5.2 planning software. They were replanned using the Varian 120 and 80 MLCs. These collimators have minimum leaf width of 3 mm, 5 mm and 10 mm at isocenter, respectively. PTV was $3.3~339.2\textrm{cm}^3$ and the number of beams was 3~7. These three plans were compared with respect to the uniformity and the conformity indices, doses to critical organ and normal tissue. Results: For the uniformity index of the planning target volume (PTV), there were no statistically significant differences between mMLCs and 120 MLCs (p=0.057) and between 120 MLCs and 80 MLCs (p=0.388). However, there was a difference between mMLCs and 80 MLCs (p<0.001). Maximum target dose to the PTV showed no dependency with respect to the leaf width. On the contrary, there were statistically significant differences in the conformity indices between mMLCs and 120 MLCs (p=0.003), between mMLCs and 80 MLCs (p=0.003) and between 120 MLCs and 80 MLCs (p=0.003). The volume of brainstem irradiated to $\geq$70% dose and to $\geq$50% dose was increased as the leaf width of MLCs increased. In particular, the volume of normal tissue irradiated is obviously changed for different leaf width. Volumetric increments for MLCs with leaf widths of 5 mm and 10 mm were 6.3% and 23.2% to the normal tissue irradiated to $\geq$50% dose, and 8.7% and 32.7% to the normal tissue irradiated to $\geq$70% dose, respectively, compared to the volume for MLCs with leaf width of 3 mm. Conclusions: The uniformity index and maximum target dose to the PTV showed no dependency with respect to leaf width of MLCs. However, the conformity index was improved as the leaf width decreased. For the sparing of normal brain tissue, treatment plans with MLCs of 3 mm leaf width is more effective, compared to ones with MLCs of 5 mm and 10 mm leaf widths.

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Clinical and Toxico-pathological Parameters for Deoxynivalenol Intoxication in B6C3F1 Mice (Deoxynivalenol에 의한 생체독성 스크리닝 및 중독증 진단지표 확립)

  • Kim, Eun-Joo;Jeong, Sang-Hee;Ku, Hyun-Ok;Kang, Hwan-Goo;Cho, Joon-Hyoung
    • Toxicological Research
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    • v.23 no.4
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    • pp.353-362
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    • 2007
  • Deoxynivalenol (DON) is a common food borne mycotoxin and occurs predominantly in grains such as wheat, barley, oats, etc. DON induces systemic health problems such as loss of appetite, emesis and diarrhea in both human and farm animals. Reliable diagnostic parameters for DON intoxication are needed to prevent deep health impact. In order to establish useful diagnostic parameters, we investigated clinical signs, hematological values, serum biochemical values, gross-, histo- and toxico-pathological findings in B6C3F1 male mice after oral administration of DON (0.83, 2.5 and 7.5 mg/kg) for 8 days. Body weight gain was significantly decreased at the highest dose of DON. Anorexia, ataxia, for crudness and lack of vigor were observed at the highest dose DON group. In hematological values, the numbers of WBC and platelets and hemoglobin content were reduced with decreased neutrophil and monocytes by 7.5 mg/kg DON. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged in a dose-dependent manner and the content of fibrinogen was elevated at high dose of DON. Of serum biochemical values, total protein, globulin, BUN, cholesterol and test-osterone were reduced but total bilirubin and albumin/globulin ratio increased. The enzyme activity of alkaline phosphatase was decreased while that of alanine aminotransferase was elevated. Relative organ weights of thymus, seminal vesicle/prostate and testes were dose-dependently reduced but those of liver and left adrenal gland increased with dose dependency. As for pathological findings, atrophy of thymus, seminal vesicle/prostate and testes and submucosal edema and ulceration in stomach and depletion of lymphocytes in thymus cortex were observed. In conclusion, these clinical, hematological, blood biochemical and patholgical parameters obtained in the present studies can be used for diagnosis of DON-mycotoxicosis, especially, low WBC, platelets, protein, BUN and testosterone and delayed prothrombin time can be available as for reliable diagnostic parameters.

The Head Scatter Factor For Quasi - small Field Sizes (준소조사면에서의 산란인자)

  • 이상공;김진기;김정홍;김부길;권형철;김정수
    • Progress in Medical Physics
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    • v.6 no.2
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    • pp.13-19
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    • 1995
  • The behavior of the correction factor associated with the collimator opening(head-scatter factor) were investigated for the 6MV x-ray beams of medical linear accelerator. The primary photon fluence was measured in air quasi-small fied size. Consideration in this study was given to the effect of head scatter factor with quasi-small fied size, the upper and lower collimator jaw scatter collection factors of quasi-small field (4-10cm) were measured with ion chamber. In general, the wedge factors which are used clinical practics are ignored of dependency on field sizes and depth. In wedge factors for each wedge filter were measured at various depth by using 6MV X-ray. In this present we inverstigated systematically the depth and field sizes dependency to determine the absorbed dose more accurately. Head scatter(upper-lower collimator jaw)appears to be (1) a small effect, less than 5% over the range of clinical field sizes (2) generated primarily at the flattening filter and therefored influenced most by the upper collimator setting.

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Effects of Relaxin and Insulin on Porcine Granulosa-lutein Cell Steroidogenesis In Vitro (체외에서 돼지 황체화 과립막세포의 스테로이드 호르몬 생산에 미치는 Relaxin과 Insulin의 영향)

  • Lee M. S.;Hossein M. S.;Lee C. K.;Kang S. K.;Lee B. C.;Hwang W. S.
    • Journal of Embryo Transfer
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    • v.20 no.1
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    • pp.71-77
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    • 2005
  • To investigate the influence of relaxin and insulin on the ovarian steroid secretion of porcine granulosa cells, we used porcine granulosa cells partially luteinized in a primary culture and examined the production of progesterone and $17{\beta}-estradiol$. Porcine granulosa cells were cultured in the presence of serum for 48 h after attachment and subsequently in the absence of serum fur 24 h. To confirm the dose dependency of relaxin or insulin, various concentrations (10, 100, 1000 ng/ml) of relaxin or insulin were added in the medium for the last 24 h, respectively. To investigate the combinational effect of relaxin and insulin, 100 ng/ml relaxin and/or 100 ng/ml insulin were added in the medium for the last 24 h in the presence or absence of luteinizing hormone (100 ng/ml). The medium was collected and used for radioimmunoassay to measure the production of progesterone and $17{\beta}-estradiol$. Relaxin or insulin increased the production of progesterone by dose dependency, respectively while they had no effect of the production of $17{\beta}-estradiol$. Relaxin (100 ng/ml) and/or insulin (100 ng/ml) significantly increased the production of progesterone in the presence of luteinizing hormone while they had no effect of the production of $17{\beta}-estradiol$. In conclusion, relaxin and/or insulin increased the progesterone secretion of porcine granulosa-lutein cells in vitro while had no effect on the production of $17{\beta}-estradiol$ and had no synergism on the effects. The effects of relaxin and/or insulin on the production of progesterone were augmented by the presence of luteinizing hormone.

Effect of Ruthenium Red and Ryanodine on Calcium Ion Metabolism in Oocyte and Early Embryo of Mouse (생쥐의 난자와 초기배아의 칼슘이온 대사에 미치는 Ruthenium Red와 Ryanodine의 영향)

  • Lee Joon Yeong;Hong Soon Cap;Kim Tae Sik;Min Byeong Yeol;Kim Haekwon;Yoon Yong-Dal
    • Development and Reproduction
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    • v.7 no.2
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    • pp.95-103
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    • 2003
  • Intracellular calcium is an important physiological factor in most cells, and ruthenium red and ryanodine play an important role as calcium modulators. Ruthenium red inhibits calcium-induced calcium release(CICR) from the intracellular calcium store. Ryanodine activates calcium release through ryanodine channel. The present experiment was performed to investigate the effects of two modulators on calcium ion metabolism and to determine their dose-dependency in oocyte and early embryo of mouse. Intracellular calcium ion concentration was measured in realtime by using confocal laser scanning microscope(CLSM) after loading of Fluo-3/AM in mouse oocytes and early embryos. Ruthenium red decreased intracellular calcium ion concentration in oocytes and early embryos at its high concentration(30, 300 $\mu$M). Ryanodine increased intracellular calcium ion concentration in oocytes and early embryos in low concentration(0.01 $\mu$M) but decreased that at higher concentrations(1, 10 $\mu$M). These results indicate that two modulators affected calcium ion metabolism in oocyte and early embryo of mouse, and their dose-dependency was different from somatic cell including myocytes.

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The Transport of a Hepatoprotective Agent, Isopropryl 2-(1-3-dithiethane-2-ylidene)-2[N-(4-methyl-thiautole-2-yl) carbamoyl] Acetate (YH439), across Caco-2 Cell Monolayers

  • Park, Hyeon-Woo;Chung, Suk-Jae;Lee, Myung-Gull;Shim, Chang-Koo
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.584-589
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    • 2001
  • Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.

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